Seeking Longer Lives; Slower Aging; Even Immortality

[Rubyait]

Imortal, perhaps not but a few thousand years at least.There is so much to discover and learn that i feel no matter how much you feel you have learned over the course of your life you would have barely touched the surface.

 

[mejane]

I may have already said this aeons ago in the early pages of this thread, but for the benefit of those whose lives are too short to (re)read all the earlier pages and also just in case I didn't actually say it and in my decrepitude only imagined it... I'll get to the point now.

If - and it's a very big if - an immortality treatment was developed then it would only be available to the very, very, rich. Now, I don't want to defame the great & and the good, but not many people get to be multi-billionaires by being nice (kind to small children, cute kittens, the starving millions... that sort of thing). So, the society of immortal humans may well consist of a few dozen incredibly self-centred individuals dancing at the end of time.

I'm glad I won't be there to see it (unless someone wants to lend me a couple of billion quid).

Jane.

 

[Mighty_Emperor]

Jane: Hmmmmmmm good point. The buggers!!!

However look at it this way - early adopters of such extreme and expensive medical technology will be the super rich but like other such developments they will basically just be acting like our guinea pigs so we can iron out the problems on a bunch of parasitic rotters

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Hunt for elixir of youth by the punk professor

ALAN MacDERMID December 06 2004

IT is not just for old times' sake that Howard Jacobs, who has just been awarded Europe's top scientific accolade, keeps up his links with his Scottish alma mater.

However, it will be old-timers who will be the first to benefit if the international research he is leading from Finland achieves its long-term goal. It could be called the elixir of youth, but Professor Jacobs preferred yesterday to call it an aspiration, a compound that would correct a range of genetic faults which speed up the ageing process.

The prize is not eternal youth, but rather an old age free from the blight of frail bones, degenerative disease and senility. Progress so far was enough to earn Profes-sor Jacobs and his colleagues in Sweden, Italy, France and Cambridge a half-share in this year's £700,000 Descartes Prize, the EU equivalent of the Nobel awards.

Professor Jacobs, 49, now based at Tampere University, left Glasgow University eight years ago, but he remains a visiting professor and is in daily e-mail contact with his former colleagues at the department of molecular genetics.

Born in London, he studied at Cambridge, Glasgow, and California, before returning to Glasgow as a reader in genetics. He regards himself as an honorary Scot, a point he underlined last week by arriving in Prague to receive the Descartes Prize in a kilt.

Teamed with a Ramones T-shirt, ear studs and a punk haircut, it left an indelible impression on Europe's great and good, but may not have surprised inhabitants of Glasgow's Robertson Building who recall the young man with camouflage trousers and Mohican cut.

"Scientists are rebels and punks are rebels," he said yesterday. "The two are not as incompatible as people believe. A lot of us are pretty eccentric, but some like to keep it under wraps. They want to avoid the mad scientist image. But I wear my eccentricity on my sleeve."

He describes his long-term aspiration as prolonging healthy old age, and emphasises that a lot more work needs to be done.

Their research is exploring the role of mutations in the mitochondria, the DNA which energises the body's cells. Everyone has some defects in these genes which accumulate over time, leading to a whole range of diseases that increase with age.

"We all have at least slight faults in our mitochondria or one sort or another, and we know these errors accumulate during life," he said.
"During our research, we artificially accelerated the ageing process in mice. It produced quite a lot of features in mice that are seen in human ageing, for example osteoporosis, hair loss, age-associated anaemia and loss of fertility. They also suffer degenerative changes in the brain and heart."

Among the common ground he shares with his former Glasgow colleagues is the role of the mitochondria in the development of deafness in the fruit fly. "I still have some collaborations with Dr Kevin O'Dell, a behavioural geneticist, on fruit flies. We use fruit fly models with defects in the mitochondrial DNA. We are testing the effect of various compounds to see if they are improving the outcomes. The Glasgow connection is alive and well."

On his move to Tampere, he explained: "When I got a readership at Glasgow, I could have stayed, but I didn't want to follow the path of one of those little sea creatures that finds a niche for itself under a rock and then quietly filter feeds for the rest of its existence. I want to make an impact on research."

He added that "Finland has many of the advantages of Scotland, and lacks many of the disadvantages. It has none of the social divisions, it is more socially cohesive, and lacking in social tension."

Source

 

[Anonymous]

Re: RYNNER, NOT RHYMER

I'm going to be dragged to the grave fighting and kicking...........

............with Wagner pumping out of massive speakers with virtually naked women whipping my coffin down the aisle).

I always forget.....is that the C of E order of service or 7th Day Adventist?

 

[Anonymous]

Re: RYNNER, NOT RHYMER

What if we can backup our personalities and have them transplanted into fast cloned bodies? It would make us a species of crazed risk takers - sky diving without a parachute so we can find out what it feels like to pan straight into the ground, going hand to hand with great white sharks, etc.

Yes, if back-up technology is available then dangerous pursuits may become commonplace entertainment, and murder become an offence against property. If someone kills you, you sue them for the cost of reincarnation.
But the same technology that allows all the memories and individuality of a person to be uploaed for storage and retrieval will also make it more eay to leave behind the body altogether;

it would be a tremendous faff getting your memories downloaded into a specially prepared blank clone; you can't download into an ordinary clone (which seems to be the Raelian strategy) because clones are people too. Downloading into your own clone would be a kind of murder.

So a better idea would be to download into a realistic robot body; you will then find that upgrades for robot bodies are easier to manage (must get the new technology) and you soon become something other than human.

Similarly an uploaded indvidual could choose to stay in the computer memory; everyone can become Neo/Smith in cyberspace. Once again you don't remain human very long.

Every path involving radical change to the human body and mind seems to lead into a whole new, scary landscape; you can't just change humanity a little bit, by extending lifespan for instance; the whole human condition changes when you start tweaking nature.

 

[Anonymous]

All very nice, but no longer really human.

Or at least, It may be human Jim, but not as we know it.

 

[Anome]

I always forget.....is that the C of E order of service or 7th Day Adventist?

It's the Unitarians. surely?

Anyway, I agree with Emperor, although I don't see where the fun in his funeral is if he's not there to see it himself. (Although I'm sure I'll be there.)

I don't want to go. I don't intend to. I'd really like to live long enough to explore a decent amount of the Universe. That takes a long time, particularly in a relativistic world.

Also, if I were to go a roamin', I might catch up on my reading. I wouldn't if I stayed here, of course, because there'd always be more to read. I need to draw a line under the total output of humanity for a few decades to catch up, then I'll have to catch up again.

There is so much to do, and I barely have enough time to do anything now.

 

[Mighty_Emperor]

More on Aubrey de Grey and a rollicking one it is:

Do You Want to Live Forever?

By Sherwin Nuland Febuary 2005




Wandering through the quadrangles and medieval bastions of learning at the University of Cambridge one overcast Sunday afternoon a few months ago, I found myself ruminating on how this venerable place had been a crucible for the scientific revolution that changed humankind’s perceptions of itself and of the world. The notion of Cambridge as a source of grand transformative concepts was very much on my mind that day, because I had traveled to England to meet a contemporary Cantabrigian who aspires to a historical role similar to those enjoyed by Francis Bacon, Isaac Newton, and William Harvey. Aubrey David Nicholas Jasper de Grey is convinced that he has formulated the theoretical means by which human beings might live thousands of years—indefinitely, in fact.

Perhaps theoretical is too small a word. De Grey has mapped out his proposed course in such detail that he believes it may be possible for his objective to be achieved within as short a period as 25 years, in time for many readers of Technology Review to avail themselves of its formulations—and, not incidentally, in time for his 41-year-old self as well. Like Bacon, de Grey has never stationed himself at a laboratory bench to attempt a ­single hands-on experiment, at least not in human biology. He is without qualifications for that, and makes no pretensions to being anything other than what he is, a computer scientist who has taught himself natural science. Aubrey de Grey is a man of ideas, and he has set himself toward the goal of transforming the basis of what it means to be human.

For reasons that his memory cannot now retrieve, de Grey has been convinced since childhood that aging is, in his words, “something we need to fix.” Having become interested in biology after marrying a geneticist in 1991, he began poring over texts, and autodidacted until he had mastered the subject. The more he learned, the more he became convinced that the postponement of death was a problem that could very well have real solutions and that he might be just the person to find them. As he reviewed the possible reasons why so little progress had been made in spite of the remarkable molecular and cellular discoveries of recent decades, he came to the conclusion that the problem might be far less difficult to solve than some thought; it seemed to him related to a factor too often brushed under the table when the motivations of scientists are discussed, namely the small likelihood of achieving promising results within the ­period required for academic advancement—careerism, in a word. As he puts it, “High-risk fields are not the most conducive to getting promoted quickly.”

De Grey began reading the relevant literature in late 1995 and after only a few months had learned so much that he was able to explain previously unidentified ­influences affecting mutations in mitochondria, the intracellular structures that release energy from certain chemical processes necessary to cell function. Having contacted an expert in this area of research who told him that he had indeed made a new discovery, he published his first biological research paper in 1997, in the peer-reviewed journal BioEssays (“A Proposed Refinement of the Mitochondrial Free Radical Theory of Aging,” de Grey, ADNJ, BioEssays 19(2)161–166, 1997). By July 2000, further assiduous application had brought him to what some have called his “eureka moment,” the insight he speaks of as his realization that “aging could be ­described as a reasonably small set of accumulating and eventually pathogenic molecular and cellular changes in our bodies, each of which is potentially amenable to repair.” This concept became the theme of all the theoretical investigation he would do from that moment on; it became the leitmotif of his life. He determined to approach longevity as what can only be called a problem in engineering. If it is possible to know all the components of the variety of processes that cause animal tissues to age, he reasoned, it might also be possible to design remedies for each of them.

All along the way, de Grey would be continually surprised at the relative ease with which the necessary knowledge could be mastered—or at least, the ease with which he himself could master it. Here I must issue a caveat, a variant of those seen in television commercials featuring daredevilish stunts: “Do not attempt this on your own. It is extremely hazardous and requires special abilities.” For if you can take a single impression away from spending even a modicum of time with Aubrey de Grey, it is that he is the possessor of special abilities.

As he surveyed the literature, de Grey reached the conclusion that there are seven distinct ingredients in the aging process, and that emerging understanding of molecular biology shows promise of one day providing appropriate technologies by which each of them might be manipulated—“perturbed,” in the jargon of biologists. He bases his certainty that there are only seven such factors on the fact that no new factor has been discovered in some twenty years, despite the flourishing state of research in the field known as biogeron­tology, the science of aging; his certainty that he is the man to lead the crusade for endless life is based on his conception that the qualification needed to accomplish it is the mindset he brings to the problem: the goal-driven orientation of an engineer rather than the curiosity-driven orientation of the basic scientists who have made and will continue to make the laboratory discoveries that he intends to employ. He sees himself as the applied scientist who will bring the benisons of molecular bi­ology to practical use. In the analogous terminology often used by historians of medicine, he is the clinician who will bring the laboratory to the bedside.

And so, in order to achieve his goal of transforming our society, de Grey has transformed himself. His “day job,” as he calls it, is relatively modest; he is the computer support for a genetics research team, and his entire official working space occupies a corner of its small lab. And yet he has achieved international renown and more than a little notoriety in the field of aging, not only for the boldness of his theo­ries, but also because of the forcefulness of his proselytizing on their behalf. His stature has become such that he is a factor to be dealt with in any serious discussion of the topic. De Grey has documented his contributions in the scientific literature, publishing scores of articles in an impressive array of journals, including those of the quality of Trends in Biotechnology and Annals of the New York Academy of Sciences, as well as contributing commentary and letters to other publications like Science and Biogerontology.

..........

Another 6 pages at:
Source

And a reply:

Aubrey de Grey Responds

By Aubrey de Grey January 18, 2005



Jason Pontin, Technology Review's Editor-in-Chief, and Brad King, Technology Review's Web editor, have invited me to respond to the trio of articles about me and my work that appear in the February 2005 issue of Technology Review with this online-only piece, in addition to a short "letter to the editor" from me that will appear in the print edition.


Dr. Sherwin Nuland's article covers three topics: (a) me, (b) the desirability of greatly postponing aging, and (c) the feasibility of doing so. In the time he and I spent together we discussed (c) very little indeed, not least because, as a physician rather than a biologist, Nuland well appreciated that he is not equipped to evaluate the difficulty of developing technologies that even I do not expect to be available to humans for at least 20 years. He notes this as follows:

"But others can challenge de Grey's science. My purpose was something else entirely.".

For reasons that remain obscure, however, Nuland later changes his mind and takes it upon himself to give a reason (not mentioned during our discussions, needless to say) why we will probably never postpone aging much:

"Unlike engineers, the adoption of whose methodology de Grey considers his main conceptual contribution to solving the problems of aging, biologists do not approach physiological events as distinct entities that have no effect on any others. Each of de Grey's interventions will very likely result in unpredictable and incalculable responses… the next thing you know, it all explodes in your face."

Engineers reading his article may beg to differ concerning whether they can successfully manipulate systems consisting of mutually interacting subsystems, and the briefest consultation of my publications will reveal that it is precisely the management of those interactions, by the judicious choice of which places to intervene, that defines my approach.

Most upmarket writers, having hit belatedly on a new reason why their subject is deluded, might have thought to raise it with that subject before risking committing such a serious error -- by some way the worst in his article, overshadowing a variety of overstatements of how far we currently are from developing some of the components of my SENS scheme.

Or if not the writer, at least the magazine's staff. By contrast, the Technology Review staff instead chose to use this offhand evaluation as the foundation for a commentary piece. They first compliment Nuland's ability to judge my science even more effusively than Nuland compliments my intellect:

"Sherwin Nuland would not be satisfied by anything less than rigorous scientific reasoning and evidence. Indeed, it's hard to imagine a writer more qualified to profile the eccentric de Grey."

And then, overlooking the facts that Nuland noted just the opposite (see above) and that his article duly offers no specifics whatsoever to back up his view that aging is essentially immutable, they buy his assertion of the impossibility of major life extension as uncritically as a child buys an ice cream -- not quite what one would expect from the staff of a serious technology publication.

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Nuland is amply qualified, however, to comment on the desirability of defeating aging -- but, curiously, he doesn't do so. He notes that he raised most of the usual concerns with me, but rather than provide or comment on my responses (which the reader can find here) he merely describes the style in which I deliver them.

The only aspect of my views on this that appears in the article is the ethical one (we have a duty to save lives). He makes only two errors in this part of the article (I, in fact, regard the choice of future global society, not the individual, as paramount and I view the role of philanthropy in advancing this work as relevant mainly to research on mice); thus, his only major failure is to recognize the contradictions inherent in his own position.

Here is a telling quote:

"I am committed to the notion that both individual fulfillment and the ecological balance of life on this planet are best served by dying when our inherent biology decrees that we do. I am equally committed to making that age as close to our biologically probable maximum of approximately 120 years as modern biomedicine can achieve, and also to efforts at decreasing and compressing the years of morbidity and disabilities now attendant on extreme old age.

"But I cannot imagine that the consequences of doing a single thing beyond these efforts will be anything but baleful, not only for each of us as an individual, but for every other living creature in our world."

I trust that if Nuland's goals are achieved soon enough for him, such that he reaches the age of 119 in the same fine shape that he is in today, he will not mysteriously forget to buy that cyanide pill to place at his bedside for the fateful moment when he wakes to find himself transformed, Cinderella-like, into a 120-year old and thus a burden on society and on himself -- but I'm not holding my breath.

Comment on February's editorial is superfluous. Pontin is as desperate as Nuland and the Technology Review staff are to put the real issues out of his mind, but unlike them he does not take the trouble to cloak this in careful words; the editorial speaks for itself all too well.

What can we conclude, observing three such egregious departures from normal logical standards by educated adults?

I can identify only one explanation: most of society is in a pro-aging trance. This is no surprise: after all, aging is extremely horrible and until a few years ago could indeed be regarded as probably immutable for a very long time indeed. Hence, a reasonable tactic was to put its horror out of one's mind, however absurd the logical contortions required.

Just as stage hypnotists' subjects provide sincere and lucid justifications for any false statement that they have been instructed is true, so most of us (not having dared to consider in detail whether aging might recently have come within our technological range) energetically defend the indefinite perpetuation of what it is in fact humanity's primary duty to eliminate as soon as possible.

Some people find stage hypnotists highly entertaining. I don't -- not any more, at least.

Source

One question that needs resolvng - why didn't melf own up to being Aubrey de Grey earlier? I have so many question to ask!!!!

 

[Mighty_Emperor]

Never Say Die: Live Forever

Associated Press

Story location: http://www.wired.com/news/medtech/0,1286,66585,00.html

03:46 PM Feb. 12, 2005 PT

WELLESLEY, Mass. -- Ray Kurzweil doesn't tailgate. A man who plans to live forever doesn't take chances with his health on the highway, or anywhere else.

As part of his daily routine, Kurzweil ingests 250 supplements, eight to 10 glasses of alkaline water and 10 cups of green tea. He also periodically tracks 40 to 50 fitness indicators, down to his "tactile sensitivity." Adjustments are made as needed.

"I do actually fine-tune my programming," he said.

The famed inventor and computer scientist is serious about his health because if it fails him he might not live long enough to see humanity achieve immortality, a seismic development he predicts in his new book is no more than 20 years away.

It's a blink of an eye in history, but long enough for the 56-year-old Kurzweil to pay close heed to his fitness. He urges others to do the same in Fantastic Voyage: Live Long Enough to Live Forever. The book is partly a health guide so people can live to benefit from a coming explosion in technology he predicts will make infinite life spans possible.

Kurzweil writes of millions of blood cell-sized robots, which he calls "nanobots," that will keep us forever young by swarming through the body, repairing bones, muscles, arteries and brain cells. Improvements to our genetic coding will be downloaded from the Internet. We won't even need a heart.

The claims are fantastic, but Kurzweil is no crank. He's a recipient of the $500,000 Lemelson-MIT prize, which is billed as a sort of Academy Award for inventors, and he won the 1999 National Medal of Technology Award. He has written on the emergence of intelligent machines in publications ranging from Wired to Time magazine. The Christian Science Monitor has called him a "modern Edison." He was inducted into the Inventors Hall of Fame in 2002. Perhaps the MIT graduate's most famous invention is the first reading machine for the blind that could read any typeface.

During a recent interview in his company offices, Kurzweil sipped green tea and spoke of humanity's coming immortality as if it's as good as done. He sees human intelligence not only conquering its biological limits, including death, but completely mastering the natural world.

"In my view, we are not another animal, subject to nature's whim," he said.

Critics say Kurzweil's predictions of immortality are wild fantasies based on unjustifiable leaps from current technology.

"I'm not calling Ray a quack, but I am calling his message about immortality in line with the claims of other quacks that are out there." said Thomas Perls, a Boston University aging specialist who studies the genetics of centenarians.

Sherwin Nuland, a bioethics professor at Yale University's School of Medicine, calls Kurzweil a "genius" but also says he's a product of a narcissistic age when brilliant people are becoming obsessed with their longevity.

"They've forgotten they're acting on the basic biological fear of death and extinction, and it distorts their rational approach to the human condition," Nuland said.

Kurzweil says his critics often fail to appreciate the exponential nature of technological advance, with knowledge doubling year by year so that amazing progress eventually occurs in short periods.

His predictions, Kurzweil said, are based on carefully constructed scientific models that have proven accurate. For instance, in his 1990 book, The Age of Intelligent Machines, Kurzweil predicted the development of a worldwide computer network and of a computer that could beat a chess champion.

"It's not just guesses," he said. "There's a methodology to this."

Kurzweil has been thinking big ever since he was little. At age 8, he developed a miniature theater in which a robotic device moved the scenery. By 16, the Queens, N.Y., native built his own computer and programmed it to compose original melodies.

His interest in health developed out of concern about his own future. Kurzweil's grandfather and father suffered from heart disease, his father dying when Kurzweil was 22. Kurzweil was diagnosed with Type 2 diabetes in his mid-30s. After insulin treatments were ineffective, Kurzweil devised his own solution, including a drastic cut in fat consumption, allowing him to control his diabetes without insulin.

His rigorous health regimen is not excessive, just effective, he says, adding that his worst sickness in the last several years has been mild nasal congestion.

In the past decade, Kurzweil's interests in technology and health sciences have merged as scientists have discovered similarities.

"All the genes we have, the 20,000 to 30,000 genes, are little software programs," Kurzweil said.

In his latest book, Kurzweil defines what he calls his three bridges to immortality. The "first bridge" is the health regimen he describes with co-author Dr. Terry Grossman to keep people fit enough to cross the "second bridge" a biotechnological revolution.

Kurzweil writes that humanity is on the verge of controlling how genes express themselves and ultimately changing the genes. With such technology, humanity could block disease-causing genes and introduce new ones that would slow or stop the aging process.

The "third bridge" is the nanotechnology and artificial intelligence revolution, which Kurzweil predicts will deliver the nanobots that work like repaving crews in our bloodstreams and brains. These intelligent machines will destroy disease, rebuild organs and obliterate known limits on human intelligence, he believes.

Immortality would leave little standing in current society, in which the inevitability of death is foundational to everything from religion to retirement planning. The planet's natural resources would be greatly stressed, and the social order shaken.

Kurzweil says he believes new technology will emerge to meet increasing human needs. And he said society will be able to control the advances he predicts as long as it makes decisions openly and democratically, without excessive government interference. But there are no guarantees, he adds.

Meanwhile, Kurzweil refuses to concede the inevitably of his own death, even if science doesn't advance as quickly as he predicts.

"Death is a tragedy," a process of suffering that rids the world of its most tested, experienced members -- people whose contributions to science and the arts could only multiply with agelessness, he said. Kurzweil said he's no cheerleader for unlimited scientific progress and added he knows science can't answer questions about why eternal lives are worth living. That's left for philosophers and theologians, he said.

But to him there's no question of huge advances in things that make life worth living, such as art, culture, music and science.

"Biological evolution passed the baton of progress to human cultural and technological development," he said.

Lee Silver, a Princeton biologist, said he'd love to believe in the future as Kurzweil sees it, but the problem is, humans are involved. The instinct to preserve individuality, and to gain advantage for yourself and your children, would survive any breakthrough into biological immortality -- which Silver doesn't think is possible. The gap between the haves and have-nots would widen and Kurzweil's vision of a united humanity would become ever more elusive, he said.

"I think it would require a change in human nature," Silver said, "and I don't think people want to do that."

Source

 

[Anonymous]

Not precisely the same thing but related:

Young Blood Gets New Meaning with Fresh Study

LONDON (Reuters) - Maybe Dracula had a point. The term Young Blood -- meaning an injection of youthful vigor -- could have a medical origin.

Scientists at Stanford University found that wiring up an old mouse to the blood stream of a young one gave a major boost to muscle recovery time in the older one.

By contrast, when old blood was pumped round the body of a young mouse, muscle recovery time became more prolonged, they said in the science journal Nature.

It was not just muscles that benefited. The same was true of the livers of older mice.

Researchers said the results suggested that the aging process lay less with the organs themselves than with the tired blood off which they fed.

I recall that "new blood grown in-vitro" was one of the antigeria treatments posited by Robert Heinlein in his Future History series.

My friend said that if the US took the Defense budget for one year and pumped it into medical research, they would discover a cure for whatever thing they targeted. I believe it. Seems like we are close in so many areas, like this one, yet they never can take the research one step further and work on practical applications.

Then again, the elderly are the biggest market for drugs in the world. So I imagine the pharmecutical firms would quash this line of research.

 

[Heckler]

Vampires Live Longer

Vampires live longer: official
By Lester Haines
Published Thursday 17th February 2005 14:53 GMT
Scientists at Stanford University have confirmed what Vlad Dracul knew all along: a refreshing dose of young blood can put the spring back into your step.

According to science journal Nature, via Wired, the Nosferatu-inspired boffins found that blood from young mice introduced into their older counterparts "activated stem cells in the old muscles that allowed them to recover from injury". The research team reckons the discovery will have implications for work on stems cells, tissue regeneration, elderly care and spinal cord injuries.

However, we should warn readers now hungrily eyeing their fellow workers' necks that it's not quite a simple matter of donning a black cape and draining the office trainee's delicious plasma - the mice in question were genetically identical, thereby avoiding the kind of immune system anarchy which would result if you connected two humans' blood supplies together.

Furthermore, the mice had their blood supplies interconnected for six weeks - an awfully long time to spend with your chops clamped round someone's neck in the stationery cupboard. Dr Thomas Rando, Stanford University School of Medicine associate professor of neurology, explained: "It's not so much about making people live longer, but if some older person gets a broken bone or skin wound, maybe we could improve their recovery rate. Maybe there's a chance to enhance the potential of old tissues."

Sadly, this interesting research comes a little too late for Hungary's Elizabeth Bathory, the literally bloodthirsty Countess believed to have killed 612 women in order to bathe in their vital essence - a sort of 16th century equivalent of slapping on Pro-Retinol-A-packed anti-ageing creams.

Bathory's activities did not impress the authorities, who imprisoned the Countess in her own torture chamber. Incredibly, she managed to live a further three years - proof, perhaps, that her methodology was sound. We feel certain that if an inconvenient incarceration had not prematurely terminated her exciting research programme she would today hold a professorship at Stanford and be delighting academia with papers such as "Rejuvenation of aged progenitor cells by exposure to the blood of Hungarian virgins".

Speaking of which, you can find the real Stanford University abstract here. ®

http://www.theregister.co.uk/2005/02/17 ... ve_longer/

It doesn't mention if these are Full vampires or 'Halft'

 

[ramonmercado]

Fast track to longevity

Fast track to longevity

Mouse study shows molecular connections between caloric restriction and lifespan extension

| By Graciela Flores

http://www.biomedcentral.com/news/20050307/01/

Researchers have moved a step forward in understanding how calorie restriction is linked to lifespan extension in mammals. In this week's issue of Nature, a group from the United States reports that SIRT1—the mammalian version of a protein linked to longevity in simpler organisms—controls glucose metabolism in mice in response to fasting.

Pere Puigserver of Johns Hopkins University and colleagues found that fasting signals induce the SIRT1 protein in the liver. This protein is one of the mammalian homologues of Sir2, known to extend lifespan in yeast and worms. SIRT1 then interacts with the coactivator PGC-1alpha, which, in turn, triggers glucose production, a key metabolic change associated with extended lifespan.

"Our work provides a novel connection between PGC-1alpha, a protein involved in the food-deprivation response, and SIRT1, a protein linked to aging in lower organisms," Puigserver told The Scientist.

SIRT1, which is an NAD+-dependent histone deacetylase, had already been associated with calorie restriction and longevity in mammals. Induced by food deprivation, it inhibits stress-induced apoptotic cell death in vitro and promotes fat mobilization in vitro and in vivo. However, it was unclear how SIRT1 might be involved in pathways such as gluconeogenesis and glycolysis, which are directly affected by calorie restriction in mammals.

In the Nature paper, the research team provides a connection between SIRT1 and these pathways. Moreover, they show that SIRT1 acts as a sensor of food deprivation.

"During starvation, there is an increase in pyruvate, a nutrient signal that induces translation of SIRT1, and an increase in NAD+, which functions as a substrate and as an activator of SIRT1. The active SIRT1 interacts with PGC-1alpha, deacetylates it, and keeps it active, promoting glucose production in the liver," explained Puigserver. With these results, the researchers showed that besides the hormonal control of PGC-1 through glucocorticoids and glucagon during fasting, there is a nutrient control as well, which targets SIRT1.

Marc Tatar of Brown University, who did not participate in the research, found the role of SIRT1 in nutrient sensing impressive. "There are hormonal inputs for sensing nutrients that are released systemically and circulate throughout the body," Tatar told The Scientist. "But what we are beginning to see is that there are also systems in which every cell can sense the nutrient condition in their own neighborhood and adjust their metabolism to their local nutrient conditions."

Tatar said this type of autonomous nutrient sensing could date back to times when organisms were only single celled and didn't have hormone signals. "These are probably the roots, and the reason that you find [this sensing system] in yeast, nematodes and mammals, is because it is very ancestral. We are looking at it in flies," said Tatar.

According to Leonard Guarente of the Massachusetts Institute of Technology, who was not involved in the study, the Nature paper provides a good example in which SIRT1 is influencing a key physiological aspect of calorie restriction in a mammal. "Although this is not the first example, it's an important one," he said.

Guarente's group recently reported how SIRT1 influences fat mobilization in mammals. "In fat cells, the target that SIRT1 is acting on is the nuclear hormone receptor PPAR-gamma, a critical regulator of fat; in this system, it's PGC-1, which is a cofactor for PPAR-gamma. This suggests we are converging in a critical pathway here."

"Calorie restriction really mitigates many diseases. Once we understand these pathways, we can think about developing drugs that can intervene pharmacologically and have implications to specific diseases," explained Guarente. "The hypothesis linking low food to longevity and disease resistance through Sir2 is robust. The testing of the hypothesis is just beginning."

Links for this article
J. T. Rodgers et al., "Nutrient control of glucose homeostasis through a complex of PGC-1a and SIRT1," Nature, 434: 113-118, March 3, 2005.
http://www.nature.com/nature

Pere Puigserver
http://www.hopkinsmedicine.org/cellbio/ ... isplay.cfm ?senduserID=182&sendpage=directory

L.P. Guarente, "Forestalling the great beyond with the help of Sir2," The Scientist, 18:34, April 26, 2004.
http://www.the-scientist.com/2004/4/26/34/1

D. Secko, "'Longevity' gene, diet linked," The Scientist, June 18, 2004.
http://www.biomedcentral.com/news/20040618/01

H.Y. Cohen et al., "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase," Science, 305:390-2, July 16, 2004.
[PubMed Abstract]

F. Picard et al., "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ," Nature, 429:771-6, June 17, 2004.
[PubMed Abstract]

Marc Tatar
http://www.brown.edu/Departments/EEB/tatar/index.htm

Leonard P. Guarente
http://web.mit.edu/biology/www/facultya ... ch/guarent e.shtml

 

[Mighty_Emperor]

Finding the Fountain of Youth

Where will UCSF biochemist Cynthia Kenyon's age-bending experiments with worms lead us?

David Ewing Duncan

Sunday, May 29, 2005

In principle, if you understood the mechanisms of keeping things repaired, you could keep things going indefinitely.

-- Cynthia Kenyon

This is the equivalent of people living for 400 years, she says, adding that there is more good news coming from her millimeter-long lab animal of choice. Our worms stay young for most of these extended life spans, she says.

Cynthia Kenyon wants to live to be 150 years old, if she's young and engaged in life. "Who wouldn't?" she asks in a breathless whisper, telling me that humans might be able to live a very long time, if not forever.

Kenyon's long, angular face is framed by straight blond hair parted in the middle. She talks excitedly, waving long, graceful fingers as her words spill out almost too fast to follow about how her lab at the University of California at San Francisco has increased the life span of tiny worms called Caenorhabditis elegans up to six times their normal life span by suppressing a single gene. This regulator gene, she tells me, in combination with other genes, appears to control an entire symphony of genes that direct aging not only in worms, but in similar genetic pathways in flies, mice and, possibly, humans.

This is the equivalent of people living for 400 years, she says, adding that there is more good news coming from her millimeter-long lab animal of choice. Our worms stay young for most of these extended life spans, she says.

"You mean this is a Fountain of Youth gene?"

She nods, delighted that I have made this connection. Kenyon talks with the slightly exaggerated facial expressions of someone telling and receiving juicy gossip -- expressions of "Oh my gosh!" and "No way!" Her voice is soft and light, and she frequently says "cool" and "neat." Yet her enthusiasm is infectious. "Life's too short to not be around nice people," she says, this woman who is delving into the mechanisms of how to make life considerably less short.

As we talk -- and she talks very quickly, as if she won't have time to say everything she wants even if she lives for 400 -- she offers me peanuts. I take a couple of nuts as Kenyon instantly shifts the topic -- she does that often -- and explains to me that she has totally changed her diet, eliminating most sugars, including those found in processed flour. Hence the peanuts. An experiment with her tiny worms is responsible, she says; that experiment proved that sugar switches on a genetic sequence that increases the amount of insulin produced by an organism, which in turn causes the body to demand more sugar. This not only adds flab to the waistline, if worms had a waistline, but also increases damage to cells in the body, speeding up the slow degradation of cells that contributes to aging. "It was a revelation," Kenyon says. She also drinks red wine and green tea, which her lab and others have shown help repair cells and contribute to an increased life span.

Kenyon's talk about immortality and a diet based on the molecular biology of a millimeter-long nematode make one wonder whether she had spent too much time at organic Zen retreats in California's Big Sur. But Kenyon is serious. Her title alone tells you this: the Herbert Boyer Distinguished Professor of Biochemistry and Biophysics at UCSF. She trained at the Massachusetts Institute of Technology and at the Laboratory of Molecular Biology (LMB) in the United Kingdom. Kenyon trained directly under the legendary Sydney Brenner, the "father" of C. elegans research. In the '60s, Brenner had chosen this tiny creature to use as a model to figure out how genes work in a simple organism. With fewer than 1,000 types of cells and a minimal number of genes for an organism with a simple nervous system and other key organs, C. elegans has the added advantage that it is translucent -- its heart, neurons and other innards can be clearly seen through a microscope.

For two decades, Brenner toiled over this little roundworm, which gave him great insight into the workings of other organisms, such as humans. Brenner also trained hundreds of young scientists at the LMB, including Kenyon, to help unfold the secrets of its genetic mysteries. In 2002, Brenner won the Nobel Prize for his work with the worms; along with two former students, John Sulston and Robert Horvitz. Nobel watchers see Kenyon as a contender for the big prize if her research holds up in higher mammals. Kenyon's work also has attracted commercial investors. In 1999, Kenyon cofounded a company with her fellow longevity expert, Lawrence Gaurante of Harvard, and Cindy Bayley, a founder of Iceland-based DeCode Genetics. Appropriately named Elixir, the Boston company has raised $36.5 million to see whether they can turn her research and that of others into a true Fountain of Youth in a pill. Some say such a pill is decades away, or impossible, and Kenyon herself admits that none of this may work with humans. But she is hopeful.

I met Kenyon in 2003, when she had extended the life span of worms by only twofold. At that time, she had just moved her lab from the main UCSF campus to the university's new silver-skinned lab complex at Mission Bay, a stretch of land in south San Francisco being revitalized beside the bay, where a sprawling navy shipyard and warehouses used to be. In her office is a copy of "Alice in Wonderland" and James Watson's classic textbook "The Molecular Biology of the Gene," along with other textbooks and journals about worms. Hanging on the wall is a framed one-page article about Kenyon from Glamour, a question-and-answer column called "Women Right Now."

"Might there be a way to put off physically aging for an extra few decades?" asked the columnist Judith Newman.

"Maintaining youthful beauty longer -- wouldn't that be great!" answered Kenyon. "All I can tell you for sure is that my worms not only acted younger, they looked younger. So you can draw your own conclusions. One thing that's likely: How you look as you age is hereditary. Some of my family members, for example, look younger than their real age. And people have mistaken me for 30, even 25."

"How old are you really?" asked Newman.

"I'm 150."

Kenyon frequently appears in the media, combining a rare ability among scientists to communicate effectively with nonscientists with a truly fantastic story. Before she worked on aging, she told the writer Stephen Hall, author of "Merchants of Immortality," hardly anyone outside the scientific community paid attention to her work. But as soon as the aging work began, she was inundated. "Night and day, night and day," she told him. "The public is absolutely fascinated by aging.

"They don't want to get old. And you can see -- read Shakespeare. Read the sonnets. They're all about aging."

I'm still skeptical until I see the evidence in a video on Kenyon's computer monitor: A normal, three-day-old worm in the prime of life, a C. elegans, is wriggling in a gelatinous broth of nutritious bacteria. At 13 days in this worm's normal life span it is sluggish, its head barely stirring as death approaches. The next images show the mutant worm tweaked by Kenyon to suppress, or "knock down" the regulator gene called daf-2. At the ripe age of 25 days, the worm is still squirming away. "This video says more than 20 Nature articles," says Kenyon.

Her original research announcing the doubling of the worm's life was published in Nature in 1993. Until her discoveries, scientists were unaware of these genes' role in regulating the highly complex process of aging, which involves hundreds, possibly thousands, of individual factors in cells and organs. Her surprising findings launched Kenyon on a decadelong quest to try to extend life span further, which culminated in an even more startling event in 2004, when Kenyon announced that her team had tweaked their worms to live up to 125 days -- the same as humans living for four centuries. Put another way, if this elongation of life works for us, Sir Isaac Newton and Cardinal Richelieu might still be alive.

To prove the youthfulness of her long-lived worms, Kenyon has developed a number of tests, including an analysis of worm tissues and cells that measures youthful traits. The 125-day worms did not show any of the telltale signs of decrepitude and frailty until the very end of their extended life. They remained vigorous, wiggling happily in their gel, as shown in Kenyon's videos. In human terms, this would mean a person would remain young for decades, growing old very slowly. It also suggests a radical new method for treating maladies of aging such as Alzheimer's, Huntington's and some cancers, which might be put off or eliminated if youth is extended. "Age is the single largest risk factor for an enormous number of diseases," says Kenyon. "So if you can essentially postpone aging, then you can have beneficial effects on a whole wide range of disease."

Other researchers have conducted versions of Kenyon's age-bending experiments to increase the life spans of flies and yeast -- and, far more significantly for humans, of mice. Conducted by Martin Holzenberger of the French Biomedical Research Agency and independently by Ron Kahn at the Harvard Medical School, the mouse tests genetically coaxed mice to live 33 percent longer than normal. These experiments are still very early, says Kenyon; she expects mouse years to be extended considerably longer as the researchers improve their techniques. The mice research is crucial because these mammals are genetically much closer to humans than are squirmy worms. The work on mice and other creatures also supports Kenyon's contention that old assumptions about life spans being fixed for each organism might be wrong. She believes that life span may be regulated by relatively simple genetic mechanisms that can be turned up (or down) by evolution almost as a volume knob is on an iPod.

Kenyon's research suggests that the daf-2 gene controls possibly 100 or so other genes that impact important mechanisms in the worm for maintaining longevity. "You can think of daf-2 as the orchestra conductor, leading the flutes, and the violins, and the cellos, each doing a little bit. So they play in concert," she says. "But what's neat is what they do.

"Some of the genes function as antioxidants -- they stop the damage done to worm cells by free radicals." Free radicals are chemical by-products of cell metabolism, mostly created by the burning of oxygen, that wreak havoc on a cell's mitochondria, DNA, proteins and enzymes by stealing electrons. Deprived of electrons, molecules then start snatching them from each other in a vicious chain reaction. Cells counterattack with free-radical-scavenging enzymes called chaperones and other damage-repair mechanisms. Over time, free radicals and other environmental toxins -- such as ultraviolet light, heat and radiation -- can overwhelm the cell's defenses, allowing the toxins to tear up DNA, rearrange and delete genes, and initiate either runaway cell growth (cancer) or cell death. Free radicals contribute to human illnesses from emphysema and some cancers to Parkinson's disease and vascular disorders. The daf-2 in worms and similar genes in humans seem to be involved in repressing the synthesis of free-radical scavenging enzymes.

Other genes in the daf-2 "orchestra" include those that help repair damaged proteins and those that fend off bacteria that can cause infections. "Still others affect metabolism," Kenyon says. "They affect fat transport and food utilization [by the cells] and things like that."

Kenyon explains that the daf-2 gene allows cells to respond to worm hormones that are similar to the human hormone insulin, which is best known for regulating how the body processes food, and insulin-like growth factor 1 (IGF-1), another hormone that influences growth. In humans and in mice there are three genes whose functions resemble those of a worm's daf-2 gene. One of them allows cells to respond to insulin, another allows cells to respond to IGF-1 and the third has an unknown function.

I ask how one gene -- or perhaps three genes in a human -- can control so much. "Maybe because that way you can make big changes in life span all at once," she says. "I believe this was a part of early evolution. It turns out that the daf-2 circuitry also allows the animal to withstand environmental stress." She explains that in worms, daf-2 is naturally suppressed in larvae during times when food is scarce and other stresses are present, and that suppression puts the worm in a dauer state, a kind of suspended animation that greatly slows aging and development until the stress has passed. Kenyon discovered that suppressing this gene after the worm has reached adulthood triggers life extension, but not in the dauer state. "This mechanism probably evolved to cope with these stresses," she says, "but once it existed it could also drive extensions of life span during evolution. This could happen by mutations that change the regulatory genes, like daf-2. Now the conductor makes the whole orchestra play forte instead of pianissimo. You see? Having everything under one system made this relatively easy to do.

"The first organism, which gave rise to all life, probably had a very short life span," she says. "But once this machinery was in place, organisms evolved to use the regulators to make big changes in life span, which also gave them advantages. For instance, humans live a thousand times longer than worms. Some creatures, such as the Galapagos giant tortoise and some species of lobsters, live to over 150 years old. It's possible that the tortoise might live considerably longer if not for predators."

And what about humans?

"It's possible that we could change a human gene and double our life span. I don't know if that's true, but we can't rule that out. I think that the difference between the life spans of different species may boil down to the activity of master regulator genes, like the daf-2 receptor. We also discovered that downstream from daf-2, the hormone receptor, is another important gene, a master transcription factor called daf-16, which binds to the many downstream genes and turns them on and off. So I bet it will be changes in those genes. And also fine tuning of the downstream genes, the chaperones, antioxidants and the rest. I doubt that humans have special genes for longevity that the worms don't have."

But these organisms are quite different from humans, I say.

"That's why it's so exciting that these experiments are working in mice, in mammals. In mice, two different research groups have shown that the homologues [similar genes in two or more species descended from a common ancestor] of daf-2 control mouse life span. Normal mice have two copies of the gene for the IGF-1 receptor, just as humans do, one copy they got from their mother and one from their father. So what one research group did was to knock out one copy. So now they have mice that have half as much receptor as normal, and they found that the mice live longer. The other group took mice and completely removed the receptor for insulin. Not IGF-1, but the insulin receptor, from the fat tissue, which is known to be an active hormone- producing tissue. They removed the insulin receptor from this tissue and extended life.

"If you trick the body into thinking it's young, and it's constantly replenishing everything, every cell," says Kenyon, "it's like building a ship where you could replace all of the parts and keep it going forever. The catch, the big catch, is that there might be things you couldn't do, you couldn't replace. Who knows?"

I ask her whether there are any side effects.

"Not for those mice, they were lucky mice. They lived longer, and they didn't get fat. That's great. That's the kind of thing we're trying to do."

I tell her this seems too easy. There must be a catch.

"We're so used to thinking that you can't get something for nothing. But why would that be true? Humans live a lot longer than dogs, and we don't suffer any penalty that I can see. We're superior in almost every way -- they can smell better. But really, they can't drive cars, they can't do half the things we can. I don't understand why you can't live longer and be really fit. Like our long-lived worms."

I ask Kenyon about the ultimate issue -- immortality.

"I think that it might be possible. I'll tell you why. You can think about the life span of a cell being the integral of two vectors in a sense, the force of destruction and the force of prevention, maintenance and repair. In most animals the force of destruction has still got the edge. But why not bump up the genes just a little bit, the maintenance genes. All you have to do is have the maintenance level a little higher. It doesn't have to be much higher. It just has to be a little higher, so that it counterbalances the force of destruction. And don't forget, the germ lineage is immortal. So it's possible at least in principle."

At 50, Kenyon looks 35. And if she is right about a treatment to slow aging, and it comes in time for her, she could be among the first generation of women to be perpetually young since Eve, the first woman, who told the hapless Adam what to do with the apple.

----------------
From the book "The Geneticist Who Played Hoops with My DNA" by David E. Duncan. Copyright © 2005 by David Ewing Duncan. Reprinted by permission of William Morrow & Co., an Imprint of HarperCollinsPublishers.

Source

 

[Rubyait]

Low fat, low protein diet boosts longevity

The idea that animals live longer if they eat less has been shown to be not entirely correct - at least in fruit flies. For these insects, it is the type of food and not just the quantity that controls their longevity.

It has been known for some time that “calorie restriction” significantly lengthens the lifespan of many non-primate species - everything from worms to fleas to mice. Linda Partridge at University College London, UK, and colleagues wanted to see if the effect was merely due to a reduction of total calories or of particular nutrients in the diet.

So the researchers divided up their Drosophila melanogaster fruit flies into four groups and put them on different diets. The control group got the standard fruit fly lab meal of yeast, which contains protein and fat, and sugar - a meal boasting about 1200 kilocalories per litre.

The second group was fed on a calorie-restricted diet, with equal amounts of yeast and sugar - about 521 kilocalories per litre. The third group was given more yeast than sugar, while the fourth group got more sugar than yeast. The latter two diets had about 860 kilocalories per litre each.

Choice meal
The flies on the calorie restricted diet lived the longest - 82% longer compared to the controls. But the flies on the higher calorie diet with reduced yeast intake did very well too.

Lowering the amount of protein and fat in the flies’ diet helped increase lifespan by nearly 65%. “It accounts for nearly all of the effect,” says Partridge. “It cannot just be calories.” Eating less sugar increased longevity only by about 9%.

Brian Kennedy, a researcher who works on calorie restriction and ageing at the University of Washington in Seattle, US, says: “It's these detailed studies that are going to unlock the secrets [of the effects of calorie restriction].”

http://www.newscientist.com/article.ns?id=dn7442

 

[Mighty_Emperor]

Who wants to live forever? Me for starters!!!

New lease of life

By programming the human body like a computer, inventor Ray Kurzweil purports to let us live forever

Clint Witchalls
Thursday July 7, 2005
The Guardian

Most people know Ray Kurzweil as an IT boffin. Not only did he invent the CCD flatbed scanner, print-to-speech software for the blind and omni-font optical character recognition, but he also created the first commercially marketed, large vocabulary speech recognition software. As if that wasn't enough, he is also known for his IT predictions. Massachuset's Institute of Technology's Marvin Minsky described Kurzweil as a "leading futurist of our time".

So it may come as a bit of a surprise that Kurzweil's latest book is about health and longevity.

Kurzweil co-authored Fantastic Voyage - Live Long Enough to Live Forever with Terry Grossman, founder and medical director of the Frontier Medical Institute, a longevity clinic. The book purports to make the scientific case that immortality is within our grasp thanks to modern technology, and that it can be reached via three so-called "bridges".

The first bridge relies on the latest medical research into ageing and how to counteract the process of getting older with "nutritionals" (food and food supplements), meditation and exercise.

The second bridge is about bioengineering and how we will soon be able to grow a new heart in situ, or be vaccinated against diseases that kill millions of people, such as cancer.

The third bridge is where we step into more familiar Kurzweil territory: it is about the benefits of technologies such as nanobots, strong artificial intelligence and full-immersion virtual reality, of the kind experienced in the Hollywood blockbuster the Matrix.

Health and technology, it turns out, have been twin passions of Kurzweil's for some time - 21 years, in fact. At the age of 35, he was diagnosed with Type 2 diabetes, and found that the necessary insulin injections made him gain weight, exacerbating his health problems. Being a restless inventor, Kurzweil wasn't about to sit around and let the condition get the better of him.

"I read all the scientific literature and came up with my own approach," Kurzweil says. "I have been free of any indications of diabetes since."

His methods might seem bizarre, but he insists there is solid reasoning behind them: to Kurzweil, reprogramming biochemistry is much the same as reprogramming computers.

"For the first time, we are actually understanding these diseases and ageing processes as information processes," he says.

Having noticed the failings of his own body, Kurzweil was a little disappointed with the inefficiencies of human body version 1.0, the flesh-and-blood creation designed by nature. Watching under a microscope, he saw his own white blood cells surround a pathogen and destroy it. But what struck Kurzweil was the sluggish response: the process of killing a germ takes more than an hour. He believes that in the future, nanobots - tiny robots implanted in our bodies - will do the same job in just a few seconds.

Neuronal responses don't impress Kurzweil either. The connections in our brain compute at 200 transactions per second, which might have served the human race well over the years, but is millions of times slower than the electronic circuits that power our computers.

Not only that, but the human body, particularly the heart, breaks down too easily. All these things can be improved, says Kurzweil, and improved through technology.

When we cross the third bridge, he says, nanobots will replace our digestive systems, we will dispense with our heart and - yes, you guessed it - replace it with nanobots that shuffle oxygen and carbon dioxide around our bodies.

In Kurzweil's future, we will be able to upgrade our bodies over the internet, downloading new programs to make us fitter, stronger and healthier. The human body version 1.0 is suited to Palaeolithic times and is urgently in need of an upgrade.

Unsurprisingly, his claims have caused consternation among some observers. And his assertion that he expects to live forever might be tactics more aimed at grabbing headlines than grabbing hold of the future.

But Kurzweil insists that the inherent risks of adopting these technologies will be worth facing. And for a 56-year-old man with a genetic predisposition to heart disease and Type 2 diabetes, he is doing pretty well. According to numerous physiological measures, Kurzweil has the body of a 40-year-old. And he's getting younger all the time.

-----------------------
www.kurzweilai.net

www.guardian.co.uk/online/story/0,3605,1522340,00.html

And the book:

Fantastic Voyage: How to Benefit from Cutting Edge Science and Add Years to Your Life
by Ray Kurzweil and Terry Grossman

PB:
www.amazon.co.uk/exec/obidos/ASIN/04522 ... ntmagaz-21
www.amazon.com/exec/obidos/ASIN/0452286 ... enantmc-20
HB:
www.amazon.co.uk/exec/obidos/ASIN/14050 ... ntmagaz-21
www.amazon.com/exec/obidos/ASIN/1579549 ... enantmc-20

 

[rynner2]

Watching under a microscope, he saw his own white blood cells surround a pathogen and destroy it. But what struck Kurzweil was the sluggish response: the process of killing a germ takes more than an hour. He believes that in the future, nanobots - tiny robots implanted in our bodies - will do the same job in just a few seconds.

Wonderful!

Except that if you get it wrong, you have the ultimate self-destruct system. Instead of auto-immune diseases like AIDS taking years to kill you, your body could self-destruct in seconds!

[Watches in horror as a person melts down into a pile of puss... :shock: ]

 

[ramonmercado]

New lifespan extension genes found

Study: New lifespan extension genes found

Researchers at the Harvard Medical School in New Haven, Conn., and the University of California-Davis report finding new genes tied to lifespan.

Drastically reducing calorie intake, or caloric restriction, is known to extend the lifespan of species including yeast, worms and rodents.

Previous research linked a gene called Sir2 with lifespan extension due to caloric restriction, but worms and yeast that lack Sir2 also live longer when put on a tough diet, indicating other genes must be at work.

Now researchers led by David Sinclair at Harvard Medical School and Su-Ju Lin at UC Davis screened for other life-extending genes in yeast. They found a gene called Hst2 that accounts for most of the difference.

Deleting Hst2 and Sir2 blocked most of the beneficial effect of caloric restriction. When Hst2 was overexpressed, so the gene was more active than normal, the yeast lived longer than normal. A third gene, Hst1, appears to act when both Sir2 and Hst2 are missing.

Sir2 and the newly identified Hst genes account for all of the life-prolonging effects of caloric restriction in yeast, Lin said.

The work was published in the Sept. 16 issue of Science.

http://www.physorg.com/news6877.html

 

[Pietro_Mercurios]

http://www.guardian.co.uk/science/story/0,3605,1645418,00.html

Geneticists claim ageing breakthrough but immortality will have to wait

· Organisms live six times longer in laboratory tests
· Cells genetically 'tricked' into slow-ageing mode

Ian Sample, science correspondent
Friday November 18, 2005
The Guardian

A genetic experiment to unlock the secrets of the ageing process has created organisms that live six times their usual lifespan, raising hopes that it might be possible to slow ageing in humans.

The geneticists behind the study say the increase in lifespan is so striking, they may have tapped into one of the most fundamental mechanisms that controls the rate at which living creatures age.

The tests were carried out in single-celled organisms, forcing them into what the researchers refer to as an "extreme survival mode". Instead of growing quickly and showing signs of ageing, the organisms became resilient to damage and were better able to repair the genetic defects that build up with age, often leading to cancer in later life.

"When you do this genetic manipulation, you can get some of the longest lifespans ever described," said Valter Longo, a biomedical gerontologist at the University of Southern California. "We have good reason to believe this genetic effect is conserved in other organisms. We're working with mice and human cells now and are already starting to see the same response."

A large body of research has already shown that severely restricting diet can boost the lifespan of flies, worms and mice by around 40%. Scientists believe that drastically cutting calories triggers a switch in an organism's behaviour, from growing and being able to reproduce, to a state of stasis in which growth and ageing are put on hold at the expense of reproductive capability, until more food is available. Scientists are now trying to mimic the effect by tinkering with genes in the hope of developing anti-ageing treatments that work without having to cut food intake.

"We're not too far from being able to exploit this understanding to at least start thinking about drugs that can put humans in an anti-ageing mode. That doesn't mean we'll necessarily live six times longer, but it means we could slow down the DNA damage we accumulate as we age, and that could protect us from cancer," said Dr Longo.

In the experiment, Dr Longo's team took yeast cells and knocked out two key genes, named Sir2 and SCH9. The latter governs the cells' ability to convert nutrients into energy. They found that instead of dying after a week, the cells lived for up to six weeks. Dr Longo said parallel experiments on human liver cells appeared to replicate the effect, but refused to elaborate until the results have been published.

...

 

[OldTimeRadio]

Live....Forever?

I asked a Christian friend of mine if he would take a pill or receive an injection, or whatever, which would permit him to live forever.

"No!!!!" he shouted, then gave me the potted lecture on "assuming the powers of God," laced with such words as "hubris," "blasphemy," "sacrilege" and so on.

But I thought a minute, took a long draw on my pipe and rephrased the qurestion, substituting "10,000 years, with options for renewal" in place of "forever."

"Yes, of course, in a heartbeat," he answered. "That's just an advance in medical science. It's NOT 'forever.'"

 

[escargot]

Watches in horror as a person melts down into a pile of puss...

Hey Ryn M8, did you mean 'pus' there?

Just asking.

 

[Pietro_Mercurios]

Watches in horror as a person melts down into a pile of puss...

Hey Ryn M8, did you mean 'pus' there?

Just asking.

We can rebuild you! :shock:

 

[OldTimeRadio]

500 Years

Can you imagine how far the "terrestrial" human race would be spread out into inter-galactic space today if such individuals as Imhotep, Aristotle and Plato, Pliny the Elder, Roger Bacon, Copernicus, Galileo, Isaac Newton, Nikola Tesla and Albert Einstein had enjoyed (or, indeed, were still enjoying), say, 500 year lifespans?

 

[ramonmercado]

Debating Immortality

Debating Immortality - 2
Biologist Aubrey de Grey still believes humans could live indefinitely -- or at least that it's worth discussing.

By Aubrey de Grey

In March 2005, Technology Review published "Do You Want to Live Forever?," an article by renowned physician and writer Sherwin Nuland that took a deeply skeptical view of the claims by Aubrey de Grey, a theoretical biologist at the University of Cambridge who believes that human aging can be "fixed." Our story elicited much lively debate among readers, including Dr. de Grey, his followers, and his critics.

Yesterday, TechnologyReview.com published an open letter by Richard Miller, MD and professor of pathology at the University of Michigan, responding to de Grey's theories (in a decidedly humorous vein). This is de Grey's response to Miller's letter. -- Editors.

Dear Rich,


How delightful to hear from you. I am so heartened that you have chosen to dissociate yourself publicly from the anti-SENS sentiment recently expressed by some of our colleagues in EMBO reports [the November 2005 issue of this molecular biology journal published a letter critical of de Grey's theories, signed by 30 or so scientists, as well as a reply by de Grey. -- Editors.]. I hope you will succeed in extracting from them an apology for including your name in the list of authors (and so outrageously parodying your inestimable writing style). Perhaps, since your name was midway down a long author list, they thought no one would notice.


What an interesting problem you raise. I confess I had not considered the hardship endured by pigs as a result of their flightlessness, but you articulate it most effectively. I think I can indeed help.


Before addressing the marketing aspect, I feel it is worth examining this problem for alternative solutions that may be even more straightforward than those you list -- and which may be applicable to those unfortunate pigs who are already alive, and so for whom your strategies 1, 2, and 5 are inapplicable. It would surely be best to alleviate as much porcine suffering as possible, so these alternatives would be a definite improvement. Further, since those who might fund your project are also already alive, this might facilitate the marketing of your idea, too.


In considering this question I have adopted the age-old strategy of looking to evolution for clues. Evolution has of course created flying creatures from flightless ones several times. However, most of these processes are thought to have been slow, progressing through long periods of aeronautical semi-competence that far exceed that of contemporary pigs. Moreover, almost all flying species share with birds most of the seven differences from pigs that you list.


However, after much research I have identified a remarkable exception to this pattern.

Amazing though it may seem, the species homo sapiens progressed, about a century ago, from a state of absolute flightlessness (unless we count floating, which you clearly do not) to one of considerable competence at flying -- and they did so over a period of only a few years. I am therefore inclined to look to the methods that our species has adopted, as a starting-point for freeing our porcine friends from their current misery.




This approach seems to be most promising. The technique employed by homo sapiens involved no alterations to their anatomy or genetics, only the use of large prostheses. These "machines" are essentially the same design when built to carry one organism or many; so they should be rather easy to adapt for porcine use, despite the anatomical differences between the two species. Further, homo sapiens has automated nearly all the operating procedures of these machines, so that a method for the pig passenger to express its desired destination may be all that is needed to complete the design.


This, however, brings me to perhaps the greatest challenge to either my proposal or yours -- namely, item six in your list of reasons why pigs remain so obstinately ground-dwelling. Pigs are well known to be among the more intelligent mammalian species. And it is a sad fact that some of the brightest among us are inclined to presume that everyone else is stupid -- so that when someone articulates an idea they do not consider obviously correct they tend to dismiss it -- sometimes even ridicule it -- without bothering to familiarize themselves with the details. (I once even encountered an American believed he could outdo an Englishman at sarcasm!)


As I'm sure you agree (and as I duly noted in my demolition of their piece in the same issue), your so-called coauthors in EMBO reports are conspicuous examples of this flaw. (Another case would be a learned immunologist's presumption that the word "allotopic" is merely a careless misspelling of the immunological term "allotypic," when, in fact, "allotopic" can be looked up in, for example, PubMed.)


These individuals are also prone to resist debate on such matters, perhaps out of a subconscious reluctance to risk the possibility of being wrong. Therefore, I fear that the intended beneficiaries of your efforts may, because of their intelligence, spurn this chance to improve their lot. They may even refuse to entertain debate on whether the "engineering solution" we offer them will work. (After all, the term "pig-headed" was not coined for nothing.)


I am confident that this can be overcome, however. The clear feasibility of adapting for porcine use a technique used to such great effect by another mammalian species can only be denied for so long. Media exposure of the absurdity of the naysayers' position will bring the public around soon enough. Such tunnel vision cannot delude people for long, no matter how great the authority of its proponent. We all meet our match some time. In particular, your characteristic eloquence on this matter will surely suffice to sway the occasional billionaire to your cause, thereby circumventing the NIH conservatism you so rightly deplore.


Best of luck!


Cheers,
Aubrey de Grey

http://www.technologyreview.com/BioTech ... 12,p2.html

 

[Mighty_Emperor]

The Quest For Immortality

Jan. 1, 2006(CBS) How’s this for an offer you can’t refuse: how would you like to live say, 400 or 500 years, or even more and all of them in perfect health? It’s both a Utopian and a nightmare scenario but there are those who say it is well within the realm of possibility.

Though we live longer and healthier lives than our grandparents, 100 is more or less the outer limit because, catastrophic disease aside, we just plain wear out. But 60 Minutes correspondent Morley Safer talked to one scientist who says that’s old-fashioned thinking, that sometime in the next 20 to 30 years or so we’ll be able to recondition ourselves for the first steps towards immortality.



We begin our journey to the outer limits with a gentle trip down the River Cam, floating by that center of British learning, Cambridge University. Our guide and helmsman: Dr. Aubrey de Grey. He ponders while he punts.

"When I was a student, I bought my own punt, a secondhand one for a few hundred pounds. And I used it in the summer to do what's called chauffeur punting," says de Grey. "People come along, tourists, and you tell them lies for money."

Today he’s pondering his favorite premise: eternal youth.

While most scientists talk about increasing longevity by a few years, de Grey says he is talking about the "indefinite extension of longevity."

"Average life spans would be in the region of 1,000 years," he says. "Seriously."

De Grey and his wife Adelaide are fixtures around Cambridge. She’s a researcher in genetics; he’s an academic maverick. While still in his early 30s he published groundbreaking work in theoretical biology and earned an international reputation. His day job is managing a fruit fly database.

But the work that consumes him involves larger game – humans. And he does his best thinking in the same 17th century pub where Watson and Crick refreshed themselves while unlocking the mysteries of DNA. De Grey believes he has unlocked the mysteries of immortality.

"The aging process is really a buildup of side effects of being alive in the first place," he says.

De Grey has identified the biological processes he thinks are responsible for aging, including the mutations that cause cancer and the gradual buildup of useless, toxic junk.

What does this accumulation of junk within the cells lead to?

"It depends on the tissue. In the eye, there is a type of junk that accumulates in the back of the retina that eventually causes us to go blind. It's called age-related macular degeneration. In the arteries, you have a different type of cell which accumulates a different type of junk that eventually causes arteriosclerosis," he says.

But de Grey has gone way beyond describing the causes of degeneration. In a series of papers he has developed a theory he calls "Engineered Negligible Senescence". Simply put, it says science will soon enable us to grow old without aging.

De Grey says that not all of the conditions that cause our bodies to age can be avoided or prevented…yet. "But I do claim that we have a fighting chance of developing ways to prevent them within the next 25 years or so."

So humans will be just as spry at 500 as we were at 25?

"If you have difficultly imaging this, think about the situation with houses. With moderate maintenance they stay up, they stay intact, inhabitable more or less forever. It’s just that we have to do a bit of maintenance to keep them going. And it's going to be the same with us," says de Grey.



But Dr. Jay Olshansky disputes de Grey's conclusions.

Dr. Olshansky studies longevity and aging at the University of Illinois in Chicago. He says de Grey’s predictions are more science fiction than science.

"Currently, life expectancy in the United States is roughly about – well, it's 80 for women, about 75 for men. They're talking about numbers that are simply way beyond comprehension," he says.

Olshanksy goes on to say that humans are simply not built to last.

"From an evolutionary perspective, we're designed to make it, to grow and develop and to reproduce, pass our genes on to the next generation, and ensure the reproductive success of our offspring," says Dr. Olshansky. "So you know, early 60s, one might argue, is where evolution has us surviving optimally. But we go well beyond that, well beyond the end of our reproductive period. So it's no surprise that we see things go wrong with these bodies when we use them beyond their warranty period. And that's exactly what we're doing."

De Grey admits his conclusions about people living to 1,000 are very extreme, "and so the natural reaction is to say, 'Well, this can't possibly be right.' But then if you look at my reasoning, how I get to those conclusions, it becomes very much harder to actually identify anything that I'm saying that is unreasonable," he says.

Would he compare such critics with those who believed that the Earth was flat and continued to believe it even when it was only theoretically proven to be round?

"I think that's a pretty good parallel, yes," says de Grey.

"I have no doubt science will make breakthroughs. But how do you develop a model or a forecast of a life expectancy based on a technology that doesn't exist?" says Olshansky.

But de Grey insists that it will exist soon enough. Our success in mapping the human genome will produce amazingly rapid strides in technology, like smart drugs designed for individuals, gene therapies to cure hereditary disease, and stem cells that rejuvenate organs like the heart and brain. And beyond that, microscopic robots that travel through our bloodstream curing what ails us.

Progress will be such that each generation will keep us one step ahead of the Grim Reaper.

"The first generation will give us maybe 30 extra years of healthy lifespan," says de Grey. "So, beneficiaries of those first therapies will still be around to benefit from improved therapies that will give them another 30 or 50 years and so on. So this is basically staying one step ahead of the problem."

But realistically, who wants to live to age 500 or 1,000?

"What I'm after is not living to 1,000. I'm after letting people avoid death for as long as they want to," he says.

And de Grey acknowledges that immortality will not be cheap. "We are talking about serious expenditure here. We are talking about expenditure in excess of what's being spent on the war in Iraq, for example."

That money will only be forthcoming when ordinary people become convinced that they have a shot at radical life extension.

"The people who are watching this probably still think about serious life extension in the same way that they think about teleportation. You know, they think it's not really foreseeable and they'll worry about it when it is," says de Grey.

That’s where the Methuselah Mouse Prize comes in. It’s a multi-million dollar contest designed by de Grey and others to spur anti-aging research. The goal is to demonstrate that radical life extension is possible by producing a so-called ‘ageless’ mouse within the next 10 years.

"And that is when the real pandemonium is going to happen because people will want to maximize their chance of making the cut," says de Grey.

Not all mice are created equal – at least not in the laboratory of Dr. Christian Sell, a research scientist at Drexel University in Philadelphia. In a separate facility, his mice come in two sizes – ‘regular’ and ‘midi’. The midi mice are 40 percent smaller than regular mice because one gene has been altered.

The altered gene, one that all mammals including humans have, regulates a hormone called IGF-1 that affects an animal’s size. If the gene is active, a lot of the hormone is produced and the animal grows large. A less active gene produces less of the hormone and a smaller animal. Dr. Sell hopes to prove that the gene also affects longevity. If he’s right, his smaller mice, with less of the hormone, will live longer than the two- to two-and-a-half year average of their larger cousins.

"Small seems to live longer, within your own species. Across species, small is shorter. Mice live shorter than elephants," says Sell. "But within mice, the smaller mice seem to live longer. Within dogs, smaller dogs live longer."

Could one conclude that this hormone produced by this gene is the longevity hormone?

"Why don't we say it's a longevity gene?" says Dr. Sell, laughing. "Because there's certainly more than that."

Three years into his research, Sell’s midi mice are living longer than the control group, but it’s too soon to tell if one of them will break the record of almost five years and win the Methuselah prize.

Is the prize stimulating longevity research?

"It's stimulating discussion," says Dr. Sell, "and whether one agrees with the idea that one will be able to intervene to radically extend life span or not, well, that's a good point for discussion."

Dr. Sell doesn't think that a fairly radical change in human longevity is a real possibility in the near term.

But it’s human nature to want to live as long as possible in reasonable health, and Olshansky says there are plenty of snake-oil salesmen out to cash in on that desire. For them he has his own prize: the Silver Fleece Award.

"This was a Silver Fleece Award for my favorite product. You know, I have my favorite, and this one was called 'Longevity.' It says here 'it drastically slows the aging process.' The person who invented it and many of the people who were listed as having used it, including John Wayne, Yul Brenner , Anthony Quinn, Russian and German party leaders and many other worldwide dignitaries, all share one common characteristic. They're dead. They have all died," says Olshansky.

So what does Olshansky say about guys like de Grey, legitimate scientists?

"What I like about Aubrey is, he's not selling anything except ideas. He's set forth a series of testable research hypotheses, which is what science is all about, and he said ‘test them’. I love that. That is what we should be doing in the world of science," Olshansky says. "I just wouldn't hold out immortality or 5,000-year life expectancies as the end result or the promise of what you're going to get from this."

But what if de Grey’s vision really does come to pass? Are we prepared to deal with a whole new set of problems?

"We're talking about saving 100,000 lives a day. And it takes a lot of problems to match that," says de Grey.

De Grey acknowledges that some people will say those 100,000 lives lost a day are just in the nature of things. "But, you know, it didn't stop us from using treatments for infectious diseases when we found out how to develop them," de Grey responds.

What about the social issues, like overpopulation, that would come with longevity?

"Sure, it will be difficult," de Grey says. "All I say is that this is a choice that the society of the future that has these therapies at its disposal is entitled to make for itself."

-------
By Bruce Ferguson © MMV, CBS Worldwide Inc.

www.cbsnews.com/stories/2005/12/28/60mi ... 8852.shtml

 

[ramonmercado]

Living Forever

Cheaper by the dozen.
By Arnaud De Borchgrave
UPI editor at large
Washington (UPI) Jan 04, 2006
Praised as the Thomas Edison of the 21st century, Ray Kurzweil was selected as one of "16 revolutionaries who made America," along with the great inventors of the past two centuries.
Forbes magazine called him "the ultimate thinking machine" and The Wall Street Journal dubbed him "the restless genius." Kurzweil is in the National Inventors Hall of Fame, With 12 honorary doctorates and the world's largest prize for innovation - the $500,000 Lemelson-MIT award. Kurzweil, now 57, published what is arguably the most blogged-about book of 2005, a 640-page blockbuster: "The Singularity Is Near," a road map to "a unique event with singular implications," or some form of immortality for those younger than 50 today.

Burwell's latest futuristic tome is the sequel to his last bestseller, "The Age of Spiritual Machines: When Computers Exceed Human Intelligence," which posited that the ever-accelerating rate of technological change would lead to computers that would rival the full range of human intelligence. He now takes his readers to the next step in this inexorable evolutionary process: the fusion of human brain and machine. Thus, "the knowledge and skills embedded in our brains will merge with the vastly greater capacity, speed and knowledge-sharing ability of our own creations."

The event Kurzweil envisages - the "singularity" - is when technological change becomes so rapid and profound that our bodies and brains merge with our machines. Singularity depicts what life will be like after the brain-machine fusion takes place and our experiences shift from real reality to virtual reality.

This moment that Kurzweil sees coming 20 years hence is when our intelligence becomes non-biological and trillions of times more powerful than unaided human intelligence. What this will mean f! or humanity is that aging can be reversed, pollution eradicated, hunger solved and our bodies and the environment transformed by nanotechnology that will also overcome the limitations of biology - and death.

Kurzweil takes human evolution far beyond today's most optimistic forecasts. These hold that anyone born today will live to be 130 and productive to 110, and those born in the 22nd century will live to 250. The glass-half-full-and-filling geomancers of the human genome research world can perceive "immortality" in the 23rd century. Kurzweil's sees the same evolution achieving a similar breakthrough for the children and grandchildren of the post-World War II baby boomers.

Bill Gates praises futurist Kurzweil and his "Singularity" as "the best person I know at predicting the future of artificial intelligence." He has a 20-year track record of accurate predictions. Bill Joy, co-founder and former chief scientist of Sun Microsystems, is f! illed with foreboding about the perils of humanity's technological future. But Joy still concedes "The Singularity Is Near" is "a clear call for a continuing dialogue to address the greater concerns arising from these accelerating possibilities."

What worries Joy in his book "Why The Future Doesn't Need Us" is that "we are being propelled into this new century with no plan, no control, no brakes."

Joy has a point. There is a growing abyss between the economic, scientific and technological knowledge of the masses and their representatives on the one hand, and, on the other, the knowledge that is required to make logical, rational and moral decisions.

Kurzweil writes that "as we reverse engineer our bodies and brains, we will be in a position to create comparable systems that are far more durable and that operate thousands to millions of times faster than our naturally evolved systems." The computational capacity needed ! to emulate human intelligence, he says, "will be available in less than two decades." Once a computer achieves a human level of intelligence, "it will necessarily soar past it." A key advantage of "nonbiological intelligence is that machines can easily share their knowledge."

Nanotechnology, now 10 years ahead of predictions and still shooting ahead, "will ultimately enable us to redesign and rebuild, molecule by molecule, our bodies and brains and the world with which we interact," Kurzweil writes.

Kurzweil the inventor developed the first omni-font optical character recognition; the first print-to-speech reading machine for the blind, the first text-to-speech synthesizer;

the first music synthesizer capable of re-creating the grand piano and other orchestral instruments; and the first commercially marketed large-vocabulary speech recognition. He has also founded and developed nine businesses in music synthesis, speech! recognition, reading technology, virtual reality, medical simulation and cybernetic art.

"Singularity," John Casti of Nature wrote, is "a mind expanding account (that) is nothing less than a blueprint for how to shove Homo sapiens off center-stage in evolution's endless play...if you buy into Kurzweil's Law of Accelerating Returns - and all empirical evidence currently available supports it completely - then the replacement of humans by machines as the primary intellectual force on Earth is indeed imminent."

George Gilder wrote, "Kurzweil's ideas make all other roads to the computer future look like goat paths to Patagonia."

http://www.spacedaily.com/news/Living_Forever.html

 

[ramonmercado]

The Longevity Dividend

FEATURE

The Longevity Dividend





Imagine an intervention, such as a pill, that could significantly reduce your risk of cancer. Imagine an intervention that could reduce your risk of stroke, or dementia, or arthritis. Now, imagine an intervention that does all these things, and at the same time reduces your risk of everything else undesirable about growing older: including heart disease, diabetes, Alzheimer and Parkinson disease, hip fractures, osteoporosis, sensory impairments, and sexual dysfunction. Such a pill may sound like fantasy, but aging interventions already do this in animal models. And many scientists believe that such an intervention is a realistically achievable goal for people. People already place a high value on both quality and length of life, which is why children are immunized against infectious diseases. In the same spirit, we suggest that a concerted effort to slow aging begin immediately - because it will save and extend lives, improve health, and create wealth.



The experience of aging is about to change. Humans are approaching old age in unprecedented numbers, and this generation and all that follow have the potential to live longer, healthier lives than any in history. These changing demographics also carry the prospect of overwhelming increases in age-related disease, frailty, disability, and all the associated costs and social burdens. The choices we make now will have a profound influence on the health and the wealth of current and future generations.

GERONTOLOGY COMES OF AGE
Gerontology has grown beyond its historical and traditional image of disease management and palliative care for the old, to the scientific study of aging processes in humans and in other species-the latter is known as biogerontology. In recent decades biogerontologists have gained significant insight into the causes of aging. They've revolutionized our understanding of the biology of life and death. They've dispelled long-held misconceptions about aging and its effects, and offered for the first time a real scientific foundation for the feasibility of extending and improving life.

ARTICLE EXTRAS

Related Articles:

Your Money for Your Life
How one company carved ifself a piece of the anti-aging industry pie

Plugging the Mitochondrial Leak

The Trouble with Markers The idea that age-related illnesses are independently influenced by genes and/or behavioral risk factors has been dispelled by evidence that genetic and dietary interventions can retard nearly all late-life diseases in parallel. Several lines of evidence in models ranging from simple eukaryotes to mammals suggest that our own bodies may well have "switches" that influence how quickly we age. These switches are not set in stone; they are potentially adjustable.

Biogerontologists have progressed far beyond merely describing cellular aging, cell death, free radicals, and telomere shortening, to actually manipulating molecular machinery and cell functions.1 These recent scientific breakthroughs have nothing in common with the claims of entrepreneurs selling alleged anti-aging interventions they say can slow, stop, or reverse human aging (see Your Money for Your Life for a peek at this industry). No such treatment yet exists.

Nevertheless, the belief that aging is an immutable process, programmed by evolution, is now known to be wrong. In recent decades, our knowledge of how, why, and when aging processes take place has progressed so much that many scientists now believe that this line of research, if sufficently promoted, could benefit people alive today.2,3 Indeed, the science of aging has the potential to do what no drug, surgical procedure, or behavior modification can do-extend our years of youthful vigor and simultaneously postpone all the costly, disabling, and lethal conditions expressed at later ages.

In addition to the obvious health benefits, enormous economic benefits would accrue from the extension of healthy life. By extending the time in the lifespan when higher levels of physical and mental capacity are expressed, people would remain in the labor force longer, personal income and savings would increase, age-entitlement programs would face less pressure from shifting demographics, and there is reason to believe that national economies would flourish. The science of aging has the potential to produce what we refer to as a "Longevity Dividend" in the form of social, economic, and health bonuses both for individuals and entire populations-a dividend that would begin with generations currently alive and continue for all that follow.

We contend that conditions are ripe today for the aggressive pursuit of the Longevity Dividend by seeking the technical means to intervene in the biological processes of aging in our species, and by ensuring that the resulting interventions become widely available.

WHY ACT NOW?
Consider what is likely to happen if we don't. Take, for instance, the impact of just one age-related disorder, Alzheimer disease (AD). For no other reason than the inevitable shifting demographics, the number of Americans stricken with AD will rise from 4 million today to as many as 16 million by midcentury.4 This means that more people in the United States will have AD by 2050 than the entire current population of the Netherlands. Globally, AD prevalence is expected to rise to 45 million by 2050, with three of every four patients with AD living in a developing nation.5 The US economic toll is currently $80-$100 billion, but by 2050 more than $1 trillion will be spent annually on AD and related dementias. The impact of this single disease will be catastrophic, and this is just one example.

Cardiovascular disease, diabetes, cancer, and other age-related problems account for billions of dollars siphoned away for "sick care." Imagine the problems in many developing nations where there is little or no formal training in geriatric health care. For instance, in China and India the elderly will outnumber the total current US population by midcentury. The demographic wave is a global phenomenon that appears to be leading health care financing into an abyss.

Nations may be tempted to continue attacking diseases and disabilities of old age separately, as if they were unrelated to one another. This is the way most medicine is practiced and medical research is conducted today. The National Institutes of Health in the United States are organized under the premise that specific diseases and disorders be attacked individually. More than half of the National Institute on Aging budget in the United States is devoted to AD. But the underlying biological changes that predispose everyone to fatal and disabling diseases and disorders are caused by the processes of aging.6 It therefore stands to reason that an intervention that delays aging should become one of our highest priorities.

HEALTH AND LONGEVITY CREATE WEALTH
According to studies undertaken at the International Longevity Center and at universities around the world, the extension of healthy life creates wealth for individuals and the nations in which they live.7 Healthy older individuals accumulate more savings and investments than those beset by illness. They tend to remain productively engaged in society. They spark economic booms in so-called mature markets, including financial services, travel, hospitality, and intergenerational transfers to younger generations. Improved health status also leads to less absenteeism from school and work and is associated with better education and higher income.

A successful intervention that delays aging would do more than yield a one-time benefit, after which, one might argue, the same exorbitant health-care expenses would ensue. Life extension already achieved among animals suggests that delayed aging may produce a genuine compression of mortality and morbidity.8 Calorie-restricted animals not only experience a reduction in their risk of death, but also experience declines in the risk of a wide variety of age-sensitive, nonlethal conditions such as cataracts, kidney diseases, arthritis, cognitive decline, collagen cross linking, immune senescence, and many others.9 If this could be achieved in people, the benefits to health and vitality would begin immediately and continue throughout the remainder of the lifespan. Thus the costly period of frailty and disability would be experienced during a shorter duration of time before death. This compression of mortality and morbidity would create financial gains not only because aging populations will have more years to contribute, but also because there will be more years during which age-entitlement and healthcare programs are not used.

A MATURING SCIENCE
Centuries ago, the French naturalist Buffon observed that aging exhibits common characteristics across species. Recent work in genetics and in the comparative biology of aging confirms these impressions and provides important clues about how to develop effective interventions that delay aging. It is now clear that some of the hormones and cellular pathways that influence the rate of aging in lower organisms also contribute to many of the manifestations of aging that we see in humans, such as cancers, cataracts, heart disease, arthritis, and cognitive decline. These manifestations occur in much the same way in other animals and for the same biological reasons.10 (For more on one example see Aging research for the dogs). Several experiments have demonstrated that by manipulating certain genes, altering reproduction, reducing caloric intake, and changing the signaling pathways of specific physiological mechanisms, the duration of life of both invertebrates and mammals can be extended.11,12 Some of the genes involved, such as PIT1, PROP1, and GHR/BP, modulate the levels of hormones that affect growth and maturation; others, such as p66SHC, help individual cells avoid injury and death. No one is suggesting that alteration of these genes in humans would be practical, useful, or ethical, but it does seem likely that further investigation may yield important clues about intervening pharmacologically.

Aging Research for the Dogs

From daschund to dane, dogs are arguably the most phenotypically variable mammalian species. That variability carries over to longevity: The tiny chihuahua can live 12-15 years compared to six or seven for its larger cousin, the Irish wolfhound. Foregoing the translation from "dog years," adding even six or seven years to the average human life span would be significant.

Dogs face many of the same age-related conditions as humans. Don Ingram at the National Institute on Aging, who leads efforts to study aging in chimpanzees (which can live up to 60 years in captivity), says that dogs are attractive models. "They are particularly useful now for skeletal and connective tissue disorders. They also get everything from loss of hearing, loss of vision, immune dysfunction, cardiomyopathies, kidney disease, and cancer."

Efforts to link genotype and phenotype for some disorders might be fruitful. Elaine Ostrander of the US National Human Genome Research Institute, who worked on the recent publication of the boxer genome, has recently shown that the extent of linkage disequilibrium in dogs is greater than in humans. This means that fewer single nucleotide polymorphisms are needed for association studies.

Nevertheless, paring down studies to the actual aging process could be difficult. Dogs have been burdened by breeders' tastes in other traits. "People would say that you can't really draw valid conclusions," says Ostrander, "because lifespan in dogs is so perturbed by interventions of man."


-Michael O'NeillGenes that slow growth in early life - such as those that produce differences between large, middle-size, and miniature dogs - typically postpone all the signs and symptoms of aging in parallel. A similar set of hormonal signals, related in sequence and action to human insulin, insulin-like growth factor (IGF-I), or both, are involved in aging, life span, and protection against injury in worms, flies, and mice, and extend life span in all of those animals. These hormones help individual cells buffer the toxic effects of free radicals, radiation damage, environmental toxins, and protein aggregates that contribute to various late-life malfunctions.

An extension of disease-free lifespan of approximately 40% has already been achieved repeatedly in experiments with mice and rats.13-16 These examples provide powerful new systems to study how aging processes influence disease expression and will yield clues about where to look for interventions that can slow aging in people in a safe and effective way. Since many of the biological pathways of aging are conserved also in simple invertebrate species such as fruit flies, it should be possible to experimentally evaluate candidate intervention strategies rapidly.

Some people, including a proportion of centenarians, live most of their lives free from frailty and disability. Genetics plays a critical role in their healthy survival. Identifying variation in these subgroups of humans holds great potential for improving public health. For example, microsomal transfer protein (MTP) on chromosome 4 has been identified as a longevity modifier in a sample of centenarians17; there is strong evidence linking a common variant of KLOTHO, the KL-VS allele, to human longevity18; and it has been demonstrated that lipoprotein particle sizes promote a healthy aging phenotype through codon 405 valine variation in the cholesteryl ester transfer protein (CETP) gene.19

Given the speed at which the study of aging has advanced and the ability to obtain research results quickly from the study of short-lived species, scientists have reason to be confident that a Longevity Dividend is a plausible outcome of aging research.

THE TARGET
What we have in mind is not the unrealistic pursuit of dramatic increases in life expectancy, let alone the kind of biological immortality best left to science fiction novels.20 Rather, we envision a goal that is realistically achievable: a modest deceleration in the rate of aging sufficient to delay all aging-related diseases and disorders by about seven years.21 This target was chosen because the risk of death and most other negative attributes of aging tends to rise exponentially throughout the adult lifespan with a doubling time of approximately seven years.22 Such a delay would yield health and longevity benefits greater than what would be achieved with the elimination of cancer or heart disease.23 And we believe it can be achieved for generations now alive.

If we succeed in slowing aging by seven years, the age-specific risk of death, frailty, and disability will be reduced by approximately half at every age. People who reach the age of 50 in the future would have the health profile and disease risk of today's 43-year-old; those aged 60 would resemble current 53-year-olds, and so on. Equally important, once achieved, this seven-year delay would yield equal health and longevity benefits for all subsequent generations, much the same way children born in most nations today benefit from the discovery and development of immunizations.

A growing chorus of scientists agrees that this objective is scientifically and technologically feasible.24 How quickly we see success depends in part on the priority and support devoted to the effort. Certainly such a great goal - to win back, on average, seven years of healthy life - requires and deserves significant resources in time, talent, and treasury. But with the mammoth investment already committed in caring for the sick as they age, and the pursuit of ever-more expensive treatments and surgical procedures for existing fatal and disabling diseases, the pursuit of the Longevity Dividend would be modest by comparison. In fact, because a healthier, longer-lived population will add significant wealth to the economy, an investment in the Longevity Dividend would likely pay for itself.

THE RECOMMENDATION
The NIH is funded at $28 billion in 2006, but less than 0.1% of that amount goes to understanding the biology of aging and how it predisposes us to a suite of costly diseases and disorders expressed at later ages. We are calling on Congress to invest $3 billion annually to this effort, or about 1% of the current Medicare budget of $309 billion, and to provide the organizational and intellectual infrastructure and other related resources to make this work.

Specifically, we recommend that one-third of this budget ($1 billion) be devoted to the basic biology of aging with a focus on genomics and regenerative medicine as they relate to longevity science. Another third should be devoted to age-related diseases as part of a coordinated trans-NIH effort. One sixth ($500 million) should be devoted to clinical trials with proportionate representation of older persons (aged 65+) that include head-to-head studies of drugs or interventions including lifestyle comparisons, cost-effectiveness studies, and the development of a national system for postmarketing surveillance.

The remaining $500 million should go to a national preventive medicine research initiative that would include studies of safety and health in the home and workplace and address issues of physical inactivity and obesity as well as genetic and other early-life pathological influences. This last category would include studies of the social and economic means to effect positive changes in health behaviors in the face of current health crises - obesity and diabetes - that can lower life expectancy. Elements of the budget could be phased in over time, and it would be appropriate to use funds within each category for research training and the development of appropriate infrastructure. We also strongly encourage the development of an international consortium devoted to this task, as all nations would benefit from securing the Longevity Dividend.

With this effort, we believe it will be possible to intervene in aging among the baby boom cohorts, and all generations after them would enjoy the health and economic benefits of delayed aging. Such a monetary commitment would be small when compared to that spent each year on Medicare alone, but it would pay dividends an order of magnitude greater than the investment. And it would do so for current and future generations.

In our view, the scientific evidence strongly supports the idea that the time has arrived to invest in the future of humanity by encouraging the commensurate political will, public support, and resources required to slow aging, and to do so now so that most people currently alive might benefit from the investment. A successful effort to extend healthy life by slowing aging may very well be one of the most important gifts that our generation can give.

S. Jay Olshansky is professor of epidemiology and biostatistics at the University of Illinois, Chicago; Daniel Perry is executive director for the Alliance for Aging Research in Washington, DC; Richard A. Miller is professor of pathology at University of Michigan, Ann Arbor; and Robert N. Butler is president and CEO of the International Longevity Center in New York.

References

1. H. Warner, "Twenty years of progress in biogerontology," National Institute on Aging, 2005.
2. R.M. Miller, "Extending life: Scientific prospects and political obstacles," Milbank Q, 80:155-74, 2002.
3. Public Agenda, "The science of aging gracefully: Scientists and the public talk about aging research," The Alliance for Aging Research and the American Federation for Aging Research, 2005.
4. E. Liesi et al., "Alzheimer disease in the US population: Prevalence estimates using the 2000 census," Arch Neurol, 60:1119-22, 2003.
5. Alzheimer's Disease Annual Report, Alzheimer's Disease International, 2004-2005; www.frost.com/prod/servlet/dsd-fact-fil ... d=38565311
6. R.N. Butler et al., "The aging factor in health and disease: The promise of basic research on aging," Special Report, Aging Clin Exp Res, 16:104-12, 2004.
7. D. Bloom, D. Canning, "The health and wealth of nations," Science, 287:1207-9, 2000.
8. M. Vergara et al., "Hormone-treated Snell dwarf mice regain fertility but remain long-lived and disease resistant," J Gerontol A Biol Sci Med Sci, 59:1244-50, 2004.
9. R.A. Miller, S.N. Austad, "Growth and aging: Why do big dogs die young?" in Handbook of the Biology of Aging, E.J. Masoro, S.N. Austad, eds., New York: Academic Press, 2006, pp. 512-33.
10. D. Sinclair, L. Guarente, "Unlocking the secrets of longevity genes," Sci Am, March 2006, [in press].
11. M. Tatar et al., "The endocrine regulation of aging by insulin-like signals," Science, 299:1346-51, 2003.
12. R. Weindruch, R.S. Sohal, "Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging," New Engl J Med, 337:986-94, 1997.
13. H.M. Brown-Borg et al., "Dwarf mice and the ageing process," Nature, 384:33, 1996.
14. K. Flurkey et al., "Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production," Proc Natl Acad Sci, 98:6736-41, 2001.
15. B.P. Yu et al., "Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics," J Gerontol, 40:657-70, 1985.
16. R. Weindruch, R.L. Walford, The Retardation of Aging and Disease by Dietary Restriction, Springfield, Ill., Charles C. Thomas, 1988.
17. B.J. Geesaman et al., "Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan," Proc Natl Acad Sci, 100:14115-20, 2003.
18. D.E. Arking et al., "Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity," Circ Res, 96:412, 2005.
19. N. Barzilai et al., "Unique lipoprotein phenotype and genotype associated with exceptional longevity," JAMA, 290:2030-40, 2003.
20. H. Warner et al., "Science fact and the SENS agenda," EMBO Reports, 6:1006-8, 2005.
21. S.J. Olshansky, "Can we justify efforts to slow the rate of aging in humans?" Presentation before the annual meeting of the Gerontological Society of America, 2003.
22. R.N. Butler, J.A. Brody, eds., Delaying the Onset of Late-life Dysfunction, New York: Springer Publishing, 1995.
23. S.J. Olshansky, "Simultaneous/multiple cause delay: An epidemiological approach to projecting mortality," J Gerontol, 42:358-65, 1987.
24. S.J. Olshansky et al., "Position statement on human aging," J Gerontol Biol Sci, 57A: B1-B6, 2002.
An Aging Drug in Our Midst?

Recent results indicate that an approved diabetes drug, metformin, may battle aging. Approved in 1995, metformin was marketed as Glucophage. Now it and generic versions are the most widely used oral medication for type II diabetes. "There is a huge natural experiment with people on metformin," says Don Ingram, of the US National Institute on Aging. And, some data are beginning to look promising.

Animal studies with metformin show increased age and reduced tumor load, and although no clinical studies are looking directly at effects on aging, a variety of ongoing clinical trials in humans are investigating type II diabetes, metabolic syndrome, liver disease, and polycystic ovary syndrome. The UK Prospective Diabetes Study 34 showed that in patients with type II diabetes, metformin treatment resulted in reductions in end-organ damage, myocardial infarction, and all-cause mortality. Stephen Spindler, professor of biochemistry at the University of California, San Diego, has shown that metformin out-performs short-term calorie restriction in inducing the gene-expression changes associated with long-term calorie restriction.

Not everyone is persuaded by the metformin results, however. Side effects, such as a small risk of lactic acidosis that can be fatal in certain patients, are not likely worth the risk of lifelong treatment for aging. Nir Barzilai at the Albert Einstein College of Medicine in New York says, "Meformin is a terrific drug used in a large prospective study to prevent diabetes, but this does not mean it has any effects on aging beyond its specific role in preventing one of the age-related diseases."


-Michael O'Neill

http://www.the-scientist.com/article/display/23191/

 

[Mighty_Emperor]

The future of old age

We're all living longer. But will this just mean more pain and immobility? Or could science cure the illnesses of old age? Alok Jha reports

Wednesday March 8, 2006
The Guardian

Every minute that you spend reading this article, the average life expectancy in Britain will rise by 12 seconds. By the time you finish reading g2, your life expectancy will have gone up by six minutes. This time tomorrow, it will have increased by almost five hours. The reason is clear: rapid advances in medicine and biology have been one of the biggest achievements of the past century and we are all living longer. Where anyone reaching the age of 60 was considered to be near death's door at the turn of the 20th century, it is barely old enough for retirement at the turn of the 21st century.

And scientists are still not holding back. Shripad Tuljapurkar, a population studies expert at Stanford University, told a recent meeting of the American Association for the Advancement of Science that, as new anti-ageing treatments become available, our species will get even older. Soon, the average age of death will jump by a year every year - five times the current rate.

While few would argue that living longer is an attractive idea, the rapid increase in the number of years begs a question: what will life be like for our increasingly elderly population? Is it such a good idea to live for an extra decade if it just involves 10 more years of illness or frailty?

"What we really want is our health expectancy to be as close as possible to our life expectancy, so that we live long and die quickly," says Lorna Layward, research manager at the charity Research into Ageing. "In other words, we [want to] compress the time we are ill at the end of our lives."

But is that possible? Getting into the specifics of this is difficult simply because each individual will have different diseases and suffer from them in a different way. The state of our bones, muscles, hearts, brains and immune systems over time depends on a range of factors, from genetics and what kind of environment we have lived in to the medical care available to us and even our level of education. But there is no doubt that getting older is the biggest single risk factor in a host of diseases from dementia to cancer.

Calculating an individual's chances of good health in old age are therefore tricky. But scientists are beginning to find that, at the population level, the time we are likely to spend ill at the end of our ever-increasing lives will drop thanks to medical advances and our increased awareness of how to stay healthy.

Quality of life is already improving for the elderly. "If you look at what a 70-year-old person is doing now versus what a 70-year-old person was doing 50 years ago, it's totally different," says Arlan Richardson, director of the Barshop Institute for Ageing and Longevity research, University of Texas. "All you've got to look at is [the astronaut] John Glenn, who went [into space] when he was 77. Three out of four of my grandparents died before they were 75 years of age, let alone going [into space]."

But long-term illness will still have to be endured by most elderly people, according to Ann Bowling, a population scientist at University College London. "Whether it's cancers or heart disease, they're not going to go away but they are becoming more treatable. People are less likely to die from those, but we're more likely to have to live with them. So people aren't necessarily dying of their heart attack, but they're living with their rheumatism instead, or even chronic cancers."

Predictions for future health expectancy have changed over the past few decades. "In the 1980s, life expectancy was increasing and the best data that we had suggested that for every increased year of life expectancy, a greater fraction was disabled life expectancy," says Richard Suzman, director of the social and behavioural research programme at the US National Institute on Ageing. "That led to a pessimistic perception that what we would see was a piling up of chronic illness and related disability, that medical science could extend life but it couldn't prevent disability or cure it."

But that world view changed suddenly in the early 1990s with the publication of a study by researchers at Duke University, who had been following the health of 20,000 people for almost a decade. They showed that disability among the elderly was not only dropping, but it was doing so at an ever-increasing rate.

Looking at their volunteers in 1994, the Duke researchers had expected a quarter of their volunteers to be disabled if rates had stayed the same as those in 1982. Instead, only 21% of the people were disabled, equivalent to 1.2m fewer disabled people than would have been without better health. According to the researchers, this represented a relative decline of almost 15%, most of it thanks to improved education on health risks and better healthcare.

This is certainly encouraging for Americans. For Britons, the picture is not as rosy. "When you look at European and US data, it seems more clear cut that there is more evidence in favour of disability-free and healthy life expectancy. In this country, the data is more cloudy," says Bowling.

Evidence presented to the House of Lords science committee's inquiry into ageing in 2002 indicated that health expectancy seems to be growing more slowly than life expectancy in Britain and that the period of debilitating illness at the end of our lives was, in fact, increasing. The Office of National Statistics, which provided the information, warned that the research was based on self-reporting of illness, so the reliability of the assessments was uncertain. Using them to project into the future would therefore be difficult.

There was a time when biologists believed ageing was controlled by some inner mechanism that imposes an upper limit on lifespan. But this explanation has fallen out of favour, replaced by the idea that ageing is simply a build-up of tiny faults and waste products as our cells go about their daily business. In addition, the body starts to streamline itself after the age of 30. Between the ages of 30 and 80, a person will lose 40% of their muscle mass, for example. Not only do we lose muscle fibres, but the ones left behind are weaker.

The story is similar with our bones: the strength and mass of the skeleton rises until the early 30s, after which men will lose about 1% of their bone mass per decade. Women lose bone at the same rate in the 10-year run-up to menopause, but, on reaching the menopause, their rate of loss jumps to about 1% per year for several years before going back to the same rate as men. "In five years, women's skeletons age by 50 years compared with men," says Tim Skerry, a professor of orthopaedic biology at Sheffield University.

Weaker muscles mean an inability to move quickly or to react appropriately to prevent a fall, for example. And weaker bones mean that they are more likely to break. Cancer is a significant cause of death in all age groups, but the absolute rate of death increases sharply with age. According to Cancer Research UK, more than 140,000 people over the age of 70 are diagnosed with cancer every year, of which more than 100,000 people in this age group die, with the most common reasons being lung, prostate, breast and colorectal cancers. If the current incidence of cancer stays unchanged, which looks likely, there will be an extra 100,000 cases diagnosed annually and the vast majority will be in those over 70.

Perhaps the most striking degradation happens to the brain. After the age of 40, the brain decreases in volume and weight by 5% every decade. This shrinkage affects people differently - while some people will be relatively unaffected, others will get more forgetful as time passes and could eventually develop Alzheimer's disease.

But the slew of drugs and treatments dealing with the problems of age continue to arrive. Researchers in the US are studying the use of anabolic steroids to build up muscle mass, for example. In the UK, Malcolm Jackson of the University of Liverpool is focusing on trying to find drugs that prevent deterioration of muscle mass in the first place. Stem cells, the body's master cells that can grow into any type of tissue in the body, could also help. "The people doing work in that area believe that it will be possible, certainly in disease states, to help replace diseased muscle. It's not a big step from that to the ageing muscle as well," says Jackson.

The damage caused to the heart in heart disease could also be repaired by studying stem cells. Understanding how the cells are made will allow the development of treatments to induce a mature heart cell to start dividing, something it would not normally do.

Skerry says that drugs to stop bones wasting away are already available. "If you have a fracture because of osteoporosis, you can prevent further bone loss. But by the time you've got a fracture, much of your skeleton is already weaker than it should be. So stopping further loss is good, but it's not the whole answer," he says.

Stimulating bone to grow again is the goal for many scientists, however. "I'm very optimistic. Current research is going very much in that direction and there are a few drugs that stimulate bone formation," says Skerry.

Arthritis, the result of wear and tear on the joints of the body, affects 7m adults in the UK and causes a great deal of long-term problems. Scientists suspect that several genes could be implicated in the development of this and related conditions - how that information will end up being used to improve life for sufferers (either in terms of drugs to target joints or treatments that work on the genes) is still an open question.

There is good news in other areas, however. Mortality rates with hip fractures are already improving: nowadays, 20% of people die a year after fracturing their hip; 10 years ago, that figure was 35%. As hip replacement procedures become more efficient (with longer-lasting replacements made of lighter materials) the trauma for the patients (who will be healthier in their old age anyway and better able to cope with such surgery) will decrease.

The sticking point to this progress could be the brain. There is no known cure for dementia as yet and leads are thin on the ground. Laboratory-based techniques trying to immunise against certain types of brain degeneration or slowing down the degradation have worked in animals but not, so far, in humans. Carol Brayne, a professor of public health medicine at Cambridge University, told the Lords' inquiry that she thought it "very unlikely that [any current technique] is going to make an impact on old-age dementia, certainly in the near future and maybe in the longer term".

Richardson has further reservations. "We have people living now who are older than we've ever had. The question is whether we've done anything about the ageing process or we're treating diseases more effectively," he says. "People in their 70s are healthier than they were 50 years ago but, on the other hand, I don't see, unless we do something about ageing, that, 20 years from now, a 70- or an 80-year-old person will be any healthier than they are now."

He argues that quality of life for the elderly will never improve dramatically until scientists look further at the mechanisms behind, rather than the symptoms of, ageing. It is a subject avoided by many scientists until recently. "Until the past five years, there was not a lot of interest in putting money into ageing research - one reason was the belief that you couldn't do anything about it," says Richardson. "The other thing is if you do slow down the ageing process, maybe that'll be bad because we'll just have more people in nursing homes."

But the tide is turning. Studies into genetic factors behind ageing have shown that there is no single gene responsible. Rather, several parts of our genome have been linked to the cumulative effect that makes us age. Restrict how much an animal eats, for example, and it will live longer. In lab experiments, rats on calorie-restricted diets were found to be physiologically younger, got diseases later in later in life and, at any rate, had less severe cases. "From the rodent models that have been looked at, the increase in lifespan is usually in the range of 15-30% maximum," says Richardson. Cutting calories is thought to trigger a switch in an animal's behaviour from normal to a state of stasis in which growth and ageing are temporarily put on hold. When food becomes available again, the animal's behaviour switches back.

Valter Longo, a biomedical gerontologist at the University of Southern California recently made yeast cells live six times longer than normal by blocking the action of two genes that, he claims, are part of the fundamental mechanism that controls how living things age. One of the genes governs the yeast's ability to convert food into energy, the other plays a role in directing energy from food into growth and reproduction, ie normal behaviour. By suppressing these two genes, the yeast cells were tricked into thinking food was scarce and forced into survival mode, living for six weeks instead of their usual one-week lifespan.

Richardson predicts that understanding the mechanisms behind calorie restriction and other genetic reasons behind ageing could be used within the next two decades to give people several extra healthy years of life. It will be a complicated field: the single-celled yeast is a simple organism and at least 10 genes have been identified that have some subtle effect on how it ages. How many genes affect ageing in humans remains to be seen.

Improving the quality of life of the elderly should be a critical part of medical research, according to Layward. "If people are well, they are not a problem. If people are healthy, they will want to stay in work, will want to be consumers, will contribute to taxes, will not be taking all their pensions," she says.

Aubrey de Grey, a biomedical gerontologist at Cambridge University, has raised hackles among scientists by suggesting that ageing could one day be stopped altogether, leading to healthy lifespans of hundreds of years. His ideas range from using stem cells to regrow diseased tissue to more left-field suggestions such as implanting people with bacteria that can clean up the waste that builds up inside cells.

Richardson says that thinking about stopping ageing is a "little bit silly" at the moment but doesn't dismiss it altogether, arguing that none of the illnesses related to ageing should be inevitable. He says that achieving longer healthy life - an average of 100 or even beyond - is all about the quality of the maintenance. "I would agree with De Grey in that respect - possibly you could stop ageing in its tracks," he says. Start with a high-quality body (and that means eating your greens, not smoking and doing lots of exercise in your younger days) and you can keep it going for longer with due care and attention. "It's like the difference between a Rolls-Royce and a cheap car".

www.guardian.co.uk/g2/story/0,,1725818,00.html

 

[OldTimeRadio]

Old People Seem Younger than They Used to Be

My first impression was that old people seem to be younger than they used to be.

But my second impression was to say to myself, idiot, you're over 60 yourself now so OBVIOUSLY elderly people are going to seem less old to you.

But then I started to discuss this issue with YOUNGER FRIENDS and they AGREED with my FIRST impression.

When I was young a 60- or 65-year-old woman was a dumpy old thing with her grey hair in a bun.

Today she's on the beach in a bikini, a knock-out figure, with younger guys around her like dogs in heat.

I don't remember any of my grandparents without grey hair. Yet I'm the same age today my grandparents were when I was in high school and my hair is still dark. There are just a few strands of grey hair around my temples which I never notice unless I'm giving myself a haircut. Where's Mendel these days?

 

[rynner2]

Scientists divided over longevity
By Rebecca Morelle
BBC News science reporter


The increase in life expectancy enjoyed by many societies is a triumph of modern science.

Our understanding of the human body and how to repair it when it breaks down have continued to push "old age" into the distance - and researchers intend to keep pushing.

But the claims made by Dr Aubrey de Grey, a scientist at the University of Cambridge, UK, that lifespan can be increased by over 1,000 years, have proven too much for some; and a dispute has now broken out within the gerontology community.

The argument, which has been played out through academic journals, and most recently at a "life extension" conference, has culminated in the unusual step of a cash prize on offer for anyone who can disprove de Grey's science.

Difficult science

Dr de Grey's claims for long life centre on SENS (Strategies for Engineered Negligible Senescence); essentially, strategies to prevent and cure ageing.

SENS is based upon repairing the molecular and cellular damage that accumulates throughout life; so as to prevent age-related illness and frailty.

It focuses on addressing seven different types of cell damage, including mutations to chromosomes and mitochondrial DNA, and cell loss. He argues that once these can be fixed or prevented, the sky's the limit for lifespan extension.

His assertions have made headlines around the world, but some gerontologists are not convinced that the science behind SENS is sound, and they spoke openly about their views at the Tomorrow's People International Conference on Life Extension and Enhancement held at Oxford University.

"Aubrey is trying to generate enthusiasm for a commitment and programme that, in a sense, sidesteps the practical challenges that the science faces," explained Professor Tom Kirkwood, co-director of the Institute for Ageing and Health, University of Newcastle.

"There are really big challenges and we are all aligned in hoping that we can harness the science to improve and extend quality of life, but it doesn't serve any useful purpose to try to extrapolate so far beyond the immediate challenges."


Twenty-eight scientists working in the field took the step of submitting a rebuttal to a paper published by Dr de Grey in the journal EMBO Reports in 2005.

The strongly worded paper says that: "Each one of the specific proposals that comprises the SENS agenda is, at our present state of ignorance, extremely optimistic...

"A research programme based around the SENS agenda... is so far from plausible that it commands no respect at all from within the scientific community."

Professor Richard Miller, associate director of the Geriatric Centre at the University of Michigan, US, told the BBC News website that he became involved with the rebuttal because he felt it was important to have on record that so many gerontologists felt that the ideas were without merit.

"I wrote the article and we sent it around to 30 or so of our colleagues, expecting that only half would sign it, because scientists really do not like to take a public position in opposition to someone that they know.

"I was amazed that we found no-one who refused on the grounds that they agreed with Aubrey; a couple of people said they didn't want to sign anything about his work because they didn't want to draw attention to it. We got 28 people who astonishingly were willing to say in public that they had evaluated the science and had found it to be worthless."

Money challenge

In response to this and other objections from the scientific community to SENS, Dr de Grey has fought back by launching the "SENS Challenge" in the Technology Review magazine of the Massachusetts Institute of Technology.

"It's essentially an offer of $20,000 (£11,000) to anyone who can write a demolition of my ideas that are sufficiently powerful to demonstrate that not only are they wrong but they are so wrong that they are unworthy of learned debate," explained De Grey to the conference delegates.

"This is open to anyone who has credentials in molecular biology of any sort, and the important thing about it is that it is judged by a review panel."

At the conference, Dr de Grey announced that he had a five-person-strong panel to review submissions, including Dr Craig Venter, who led the private effort to decode the human genome, and Dr Nathan Myhrvold, a former chief technologist at Microsoft.

"I essentially felt that it was critical for me to smoke out the opposition," Dr de Grey told the BBC News website.

"I had to move things along to an on-the-record opposition so that people would be forced not simply to say what they thought of these ideas, but why."

So far, there have been very few submissions to the challenge, and none of these from the scientists involved with the EMBO rebuttal.

"Most scientists, and I was among this group, took the position that any sort of response to de Grey was just feeding the fire," said Professor Miller, explaining why he had chosen not to enter the challenge.

But while the debate continues, all involved do agree that life extension is within the realms of possibility for science; but how exactly we do it, how long we can postpone death for, and whether modern society can handle the burden of an increasingly aged population is still being debated.

"I think we will hopefully be able to get some means to make a significant impact on processes of ageing. These will not necessarily result immediately in substantive life extension, but they may change the profile of health that people experience as they go through [old age]. We haven't begun seriously to discus what should be our priorities and how we should develop strategies," explained Professor Kirkwood at the conference.

"Most medical research is done by trying to prevent people dying. And Aubrey says we should simply extend this into ageing. Actually, now, we are in a situation of being able to harness what comes from the basic biomedical research to try to devise a better way to age.

"And if that leads to life extension, that's great. But it's difficult to see the path to make that happen."

http://news.bbc.co.uk/1/hi/sci/tech/4834128.stm

(I still think this thread should be in The Human Condition -
pester the Mods if you agree! 8) )

[Emp edit: Well this post should have gone into this thread so I've snipped it out and moved it over]

 

[ramonmercado]

Longevity

Eat less, live more

Apr 20th 2006
From The Economist print edition


How to live longer—maybe








DIETING, according to an old joke, may not actually make you live longer, but it sure feels that way. Nevertheless, evidence has been accumulating since the 1930s that calorie restriction—reducing an animal's energy intake below its energy expenditure—extends lifespan and delays the onset of age-related diseases in rats, dogs, fish and monkeys. Such results have inspired thousands of people to put up with constant hunger in the hope of living longer, healthier lives. They have also led to a search for drugs that mimic the effects of calorie restriction without the pain of going on an actual diet.

Amid the hype, it is easy to forget that no one has until now shown that calorie restriction works in humans. That omission, however, changed this month, with the publication of the initial results of the first systematic investigation into the matter. This study, known as CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), was sponsored by America's National Institutes of Health. It took 48 men and women aged between 25 and 50 and assigned them randomly to either a control group or a calorie-restriction regime. Those in the second group were required to cut their calorie intake for six months to 75% of that needed to maintain their weight.


The CALERIE study is a landmark in the history of the field, because its subjects were either of normal weight or only slightly overweight. Previous projects have used individuals who were clinically obese, thus confusing the unquestionable benefits to health of reducing obesity with the possible advantages of calorie restriction to the otherwise healthy.

At a molecular level, CALERIE suggests these advantages are real. For example, those on restricted diets had lower insulin resistance (high resistance is a risk factor for type 2 diabetes) and lower levels of low-density lipoprotein cholesterol (high levels are a risk factor for heart disease). They showed drops in body temperature and blood-insulin levels—both phenomena that have been seen in long-lived, calorie-restricted animals. They also suffered less oxidative damage to their DNA.

Eric Ravussin, of Louisiana State University in Baton Rouge, who is one of the study's authors, says that such results provide support for the theory that calorie restriction produces a metabolic adaptation over and above that which would be expected from weight loss alone. (He also points out that it will be a long time before such work reveals whether calorie restriction actually extends life.) Nevertheless, such metabolic adaptation could be the reason why calorie restriction is associated with longer lifespans in other animals—and that is certainly the hope of those who, for the past 15 years, have been searching for ways of triggering that metabolic adaptation by means other than semi-starvation.

The search for a drug that will stave off old age is itself as old as the hills—as is the wishful thinking of the suckers who finance such efforts. Those who hope to find it by mimicking the effect of calorie restriction are not, however, complete snake-oil salesmen, for there is known to be a family of enzymes called sirtuins, which act both as sensors of nutrient availability and as regulators of metabolic rate. These might provide the necessary biochemical link between starving and living longer.



An elixir of life?
Boosting the activity of sirtuins in yeast, nematode worms and fruitflies (three rapidly reproducing stalwarts of biological laboratories) does indeed result in longer lifespans. In 2003 a team led by David Sinclair of Harvard Medical School described 19 plant-derived molecules that activate sirtuins in yeast. One of these molecules, resveratrol, is found in red wine—which created excitement among those who think that a wine-rich diet is part of the explanation for the healthy old age apparently enjoyed by many who live in southern Europe.

In February, a group led by Dario Valenzano of the Scuola Normale Superiore in Pisa, Italy, showed that the effect applies in vertebrates, too. Dr Valenzano's experiments with resveratrol increased the maximum lifespan of a small fish, called Nothobranchius furzeri, by 60%. (Nothobranchius furzeri was chosen because it is the shortest-lived vertebrate known, with a normal maximum lifespan of 12 weeks.)

Resveratrol, however, is only a starting point. Sirtris Pharmaceuticals, a firm based in Cambridge, Massachusetts, of which Dr Sinclair is a co-founder, has identified a number of synthetic molecules whose effect on yeast is many times more potent than resveratrol's. Although there is, as yet, no published evidence that sirtuins extend life in mammals, or that resveratrol activates sirtuins in human cells, some of these molecules are already in clinical trials for safety.

Moreover, Dr Sinclair thinks he knows why plant molecules such as resveratrol might affect longevity in animals. Resveratrol is produced when a vine is under stress—for example, due to dehydration or over-exposure to sunshine. According to Dr Sinclair's theory, which he calls xenohormesis, animals rely on such botanical stress signals to give them extra information about their own environments, in the same way that the alarm calls of one species warn others of danger. If bad things are happening to plants, he surmises, that is a reason for pre-emptive animal action. Animal bodies thus react to molecules such as resveratrol by activating their own defence mechanisms. These, in turn, protect their cells from stress-related damage.

Xenohormesis is a variation of a more general theory, hormesis, which interests Suresh Rattan of Aarhus University in Denmark. A good example of hormesis is exercise. In theory, this should damage cells because it increases oxygen uptake, and oxidative stress is bad for things like DNA. Of course, exercise is not actually bad for cells—and the reason is that the body activates defence mechanisms which overcompensate for the stress the exercise creates, producing beneficial effects. So, while chronic stress is always bad for you, a short period of mild stress followed by a period of recovery can be good.

Many of the health benefits of exercise are thought to be due to the synthesis of damage-controlling molecules called heat-shock proteins, and Dr Rattan's group has been experimenting with other ways of triggering these proteins. He has found, for example, that taken in combination with exercise, a spice called curcumin boosts the production of heat-shock proteins several-fold.

According to Dr Rattan, such interventions improve the function of a cell over time, and in doing so, may produce clinical benefits such as protection against neurodegenerative diseases. Resveratrol may also produce benefits, he says, but how it does so is not yet clear. He disagrees with Dr Sinclair over the existence of a regulatory pathway for longevity in which sirtuins play a key role. In his view, ageing is about the accumulation of damage, and is not under tight genetic control. Sirtuins will, he says, probably be but a small part of a more complicated picture.

Dr Rattan also doubts whether calorie restriction will extend maximum human life expectancy. He argues that the concepts of ageing and longevity must be separated. It may, indeed, be possible to reduce or eliminate particular age-related diseases, and that would increase average lifespans in the way that eliminating other diseases has done in the past. But this is not the same as slowing down ageing itself, and thus increasing maximum lifespans. Longevity is a more complex trait than any individual disease, and, in his opinion, it will not be altered so easily.

Cynthia Kenyon, a researcher at the University of California, San Francisco, and a co-founder of Elixir Pharmaceuticals, another company looking into anti-ageing drugs, believes that molecules such as resveratrol are likely to be approved in the next five to ten years, for use as prophylactics against age-related diseases. People then will start taking them, and a huge natural experiment will get under way. If Dr Rattan is wrong, maximum lifespan as well as average lifespan will increase. If he is right, at least people will enjoy a healthier old age.



http://www.economist.com/science/displa ... id=6823498