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Then in 1988 a miracle happened -- the University of Colorado's Thomas Johnson reported that a gene mutation in nematodes could more than double their life spans. Five years later, Cynthia Kenyon at the University of California, San Francisco, nailed a similar worm "gerontogene" dubbed daf-2. These flabbergasting discoveries revealed that not everything about aging is intractable chaos -- worms, at least, apparently possessed gene-encoded modules poised to oppose the ravages of advancing age when activated by a single mutation. Optimists soon speculated that similar modules exist in mammals.
But for several years after the discovery of worm gerontogenes, it wasn't at all clear that mammals possess such modules. After all, daf-2 and related genes were known to work by activating a semblance of the "dauer phase," a kind of suspended animation that enables nematode larvae to ride out food shortages, and there's a lack of evidence that we warm-blooded types similarly turn into living mummies when the larder is bare. But then two remarkably persistent scientists settled the burning issue -- and solved a murine murder mystery in the process.
One was Andrzej Bartke, an endocrine researcher at Southern Illinois University in Carbondale who'd long nurtured the world's only colony of Ames dwarfs -- mice whose growth is stunted by a mutation in the prop-1 gene, which curtails the production of growth hormone. The dwarfs were widely regarded as delicate, short-lived runts. But Bartke disagreed. He'd watched giant transgenic mice, which over-express growth hormone, undergo what seemed accelerated aging, and so had guessed that his dwarfs' hormone deficiency might actually boost their longevity.
Proving his hunch wasn't easy. Mammalian life span studies are the grueling marathons of life science. Conducting one with normal mice typically takes two to three years; Bartke knew that proving his dwarfs' age slowly could easily take more than four. That represents perhaps 15 percent of a researcher's entire career. And history has repeatedly shown that the length of such experiments increases the risk that diseases or stresses will crop up that shorten the rodents' lives and ruin everything. Still, in 1993 Bartke and two postdocs pitted 34 Ames dwarfs against 28 of their normal siblings in a slow race to the death. A little over three years later, their data showed that the dwarfs were living 50 percent longer than the controls.
But while preparing to report the discovery, Bartke learned that researchers at The Jackson Laboratory in Maine had earlier found that Snell dwarfs -- mutant mice nearly identical to Ames dwarfs -- were short-lived. Fearing his lab's contrary finding would be dismissed as a fluke, he phoned Kevin Flurkey, the Maine lab's dwarf mouse keeper, to compare notes. It turned out that despite the earlier findings, Flurkey had a hunch about the dwarfs' longevity and had more recently launched a new life span study on them. After 18 months, his data had indicated the females were strikingly long-lived, but the males were dying very young.
Then one day Flurkey had witnessed one of his male "caretaker" mice -- normal mice caged with the easily-chilled dwarfs so they can snuggle up and keep warm -- apparently trying to throttle a dwarf. Suddenly it clicked: He'd always caged his dwarfs with same-sex caretakers, and male mice have been known to kill pups sired by other males. Further, adult dwarf mice resemble pups. No wonder his Snells had generally seemed short-lived -- lots of them were being murdered in the night by mice three times their size. Not long before Bartke phoned, he'd realized what was happening and placed his surviving Snell males with female caretakers, where they'd lived happily ever after -- or at least a lot longer than the controls.
Bartke and Flurkey wound up extending the gerontogene revolution to mammals, and now more than a half dozen gene mutations are known to boost mouse longevity. While it's not known whether human gerontogenes exist, the mouse discoveries argue that an ancient, evolutionarily conserved anti-aging module is likely embedded in our genomes that could dramatically extend our healthy life spans if cleverly tweaked with drugs. Last year another landmark mouse study gave an exciting hint that the module is coming into view: Researchers showed for the first time that a drug could convincingly extend life span in mammals. Called rapamycin, the drug inhibits mTOR, a gene found in all mammals, suggesting that it may be a key part of an anti-aging module that can be readily manipulated.
The Youth Pill: Scientists at the brink of an anti-aging revolution, by David Stipp, Penguin Books, London, 2010. 320 pp. ISBN: 978-1-617-23000-4. $26.95.
David Stipp is a freelance science writer, formerly with the Wall Street Journal and Fortune, who has extensively covered gerontology since the late 1990s. One of the key inspirations for his new book on the topic was a 2006 article in The Scientist calling for pursuit of the "longevity dividend" promised by anti-aging research. He recently launched a blog on aging science at his website, www.davidstipp.com.
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[June 2010]
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[Comment posted 2010-06-27 22:01:46]
[Comment posted 2010-06-26 11:21:01]
As to why larger animals age and die - I suggest it is an anti-cancer trick of evolution.
[Comment posted 2010-06-26 07:58:13]
Most of the diseases of aging are not seen in youth, thus to avoid the ravages of aging, it will be necessary to maintain youth.
The prime diseases of aging, Alzheimer, Parkinson's in the brain, atherosclerosis in the vascular system, osteoarthritis in the skeletal system, cataracts in the eyes as well as macular degeneration in the retina are all related to aging.
Finding the key for maintenance of youth will probably be necessary to avoid the ravages of aging.
Does this mean extending puberty or that state prior to reproduction for true longevity to occur, or to extend childhood? Possibly.
With the current state of modern technology, I think most likely a continued and extended state of symbiosis between man and machine, with pacemakers, defibrillators, even artificial hearts, kidneys and lungs being developed for implantation. We are seeing the dawn of such an age. Is it an age people will choose to live?
Certainly now people are choosing to live in symbiosis with machines, and are becoming in closer relationships with them.
It will require continued research and development, which is enormously expensive.
Will only those of great wealth be the beneficiaries, possibly so. Currently those with wealth are more likely to live longer than those in poverty, and such a trend can be expected to continue.
I think possibly the ancient stories of longevity such as Methuselah in the Bible who lived nearly a thousand years may have some basis in fact, perhaps persons who lived for extended periods of time in a more pristine environment.
Does that mean something has been lost, perhaps a genetic heritage which might be regained or rediscovered? Possibly so.
I think it is worth a look, although it would require time, effort and commitment, all things in short supply in modern times.
There is more commitment to destruction, war, domination and the search for wealth rather than for those things leading to truth and beauty.
First the priorities must be set, then the quest can begin, however the destination may not be that which is expected or even hoped for.
Thanks
[Comment posted 2010-06-25 14:48:39]
[Comment posted 2010-06-25 14:05:40]
There have been immense developments in scientific research, which includes medical science as well. There has evolved a whole novel understanding of the biology of ageing. A vast body of knowledge can explain the changes that take place with ageing at molecular and cellular level. At the same time, the progress in health care and technology makes it possible to slow ageing. There are possibilities of being able to reverse the ageing process.
The hopes apart, any sort of life extension may be complicated with undesirable outcomes. The readers may find interesting to go thr' a chapter, "DARKER-SIDE OF LIFE EXTENSION:
The Tithonus Option, Etc." from my book, "Ageing slowly, Living longer". I am reproducing the same here.
CHAPTER TWELVE
DARKER-SIDE OF LIFE EXTENSION:
The Tithonus Option, Etc.
THE FEARS ASSOCIATED
WITH EXTENDED LIFE
Future technology appears to offer us
visions that rival the dreams of myth and
legend. As per the Clarke's Law: ?any
sufficiently advanced technology is
indistinguishable from magic.? One of these
dreams is that of extended life. It appears
that with the advancements in medical
science, genetics, biotechnology, coupled
with those in nano-science, a true extension
of human lifespan will come in the near
future. However, it may come at a price.
The Tithonus Option:
There is a fear that the anti-ageing
technology may present us with the
extended lifespan but limited improvement
in quality of life. The nightmare, that we will
live longer, but in bad health and mental
deterioration, has been called Tithonus
option - immortal life with sub-functional
brain or eternal dementia.
The Story of Tithonus: Tithonus was a
mortal, who fell in love with Eos, the
goddess of the dawn in Greek
mythology. The goddess, Eos, knowing that the mortal,
Tithonus was destined to age and die,
begged Zeus, the supreme god of ancient
Greek mythology and counterpart of Roman
god Jupiter, to grant her lover an immortal
life. Zeus, the jealous god, granted the wish
but not the eternal youth. Tithonus aged,
becoming increasingly debilitated and
demented, eventually driving Eos to
distraction. In despair, she turned Tithonus
into a grasshopper. In Greek mythology,
the grasshopper is immortal.
There are several foreseeable outcomes
from the anti-ageing technology. Today, the
majority of people living in the developed
countries can expect to live well into their
seventies. Even so, the final years are
usually marked by impaired health and
often senile dementia. Here, three possible
futuristic outcomes may seem probable:
The first, we will live and die as we do
today. There may accrue no benefit of
ageing research. The second possibility,
called the Tithonus option, is that the
technology will give extended lifespan but
will not be able to reduce prevalence of
dementia and debility. The third possibility
is that technology will be able to repair the
damage done with age to our
tissues, including neurons, thus granting us
longevity with good quality of life.
Life on Support Systems:
In the intensive care units, it is
commonly seen that for the critically ill
patients, more and more invasive procedures
are performed to save the life and more and
more of vital functions are taken over by biomachines.
The ventilator drives the
respiration, bolus and continuous infusion of
intravenous fluids and drugs provide the
nutrition and support the vital functions.
Sometimes, the heart and lung machine
takes over. The person is considered living till
the brain functions. It is an artificially
prolonged life on support systems, amounting
to a nightmare of proportion of the Tithonus
option: a long life, with zero quality of life.
Superficially, this may seem a possibility.
While genetic engineering and nanotechnology
may help in extending the life
significantly, it does not follow that future
technology will be able to repair all wear-andtear
on the brain and body organs. If the
future technology can not repair all
microscopic injuries, the Tithonus option will
result. Just consider the renal disease
patients in whom the kidneys have totally
failed, they are maintained on dialysis since
even a poor-quality-of-life is better than no
life. Will we not fall in the same trap, finally
conciling ourselves to Tithonus option? People
may regard it better than cryopresevation in
hope of a novel treatment in the remote
future. Thus, the Tithonus option is feared.
The optimistic scientists, though, think that
the Tithonus Option is not a likely outcome
for various reasons.
THE FUTURE VISIONS
AND THE GURSKY OPTION
Current patterns of death: The
death rate increases exponentially because
our bodies accumulate damage. The
accumulated mutational load over time leads
to errors in DNA leading to cancer. It takes
years of accumulated mutations for cells to
become cancerous.
The vascular disease is the result of
narrowing and plaque deposition in arteries
because of the atherosclerosis process. The
heart attack occurs when blood supply is
interrupted to a part of heart. The stroke
occurs when a clot breaks off from an arterial
plaque and lodges in an artery supplying a
part of brain. A stroke can also occur when
an artery bursts in the brain, pouring out
blood under pressure. The resulting blood clot
damages brain tissue by a direct pressure
effect. As such, the vascular disease
represents an example of accumulated
errors.
The accidental deaths follow a complex
curve. Young people are more likely to die of
accidents than those older. This is due to the
higher prevalence of risk-taking behaviours.
As the age increases, there comes awareness
for safety. The elderly, too, are more likely to
die because of accidents. Reduced balance
and co-ordination, delayed response,
muscular weakness and osteoporosis put the
elderly at greater risk of having an accident.
But, here, the accidental deaths show an
exponential curve because, they are the
result of accumulated damage.
The Gursky option: The diseases of
accumulated damage are destined to be the
primary causes of death in developed
countries. Also, with development, other
countries will reduce the rate of infections,
falling for the death patterns like in
developed countries.
The only possible escape from the
diseases of accumulated damage, is
developing advanced medical technologies
capable of repairing the bodily errors. This
is called the Gursky option. So named after
Ian McDonald's novel, The Days of Solomon
Gursky, where the life of a nanotech
designer?s inventions allow humans to stave
off disease and improve their bodies.
The exponential death rates and
increasing debility go hand in hand. By
solving one, the other shows a favorable
trend. By decreasing cancer and accident
deaths, we can look forward to reduce
debility. Therefore, developing the antiageing
technology will not lead to the
Tithonus option but rather the Gursky
solution.
EFFECTS OF EXTENDED
LIFESPANS ON THE SOCIETY
THE VISION OF LIFE EXTENSION
To stay alive is a basic human drive. It is
a precondition for all other activities. Lifeextension
is the natural progression of curing
diseases by treatment and preventing the
effects of ageing altogether. The human life is
sacred and should be cherished and
preserved.
THE FEARS OF SOCIAL BURDEN
The extended life spans will definitely
affect human society. It will bring positive
effects on society of a host of people with the
wisdom of 150 years of life and the youthful
vitality.
The issue of overpopulation should not
be feared. In technologically advanced
societies, couples tend to have fewer
children, often below the replacement rate.
By spread of benefits of technology,
education, and women?s rights, fertility rates
will decline. As the UN population studies
predict, over-population is an unlikely
problem.
Life extension will not place a burden on
health care, as feared. The life extension,
itself, is likely to be associated with good
health and disability limitation. The older
adults with extended life will be economically
productive members of society.
BORING LONG LIFE? NOPE.
People on learning life extension
projects, or sometimes, even scientists, air
the fear that living very long may be boring.
But, feeling bored is a state of mind. The
state is never permanent, it is a transient
phase influenced by immediate situations. We
discover new things, find something hidden in
the things known for long and feeling of
boredom passes away, replaced by the joy of
excitement.
THE NON-AGEING WORLD
By eliminating a majority of age-related
diseases and maintaining the vitality of the
body for a very long time, we can look
forward to achieve a significantly long life
span of more than 1,000 years.
This estimation of future average life
span of 1,000 years has been reached by
considering the removal of age-related
mortality from current statistics. Accidents
and other such causes of death will still
remain.
The anticipated problem of overpopulation
apart, there will be the danger
that people considered threats, someone like
Hitler and Stalin will remain in power much
longer than they would if they faded away or
died because of ageing. Criminals, too, would
live longer like characters in cartoon films,
continuing to pose a threat.
The delayed ageing will lead to various
social changes. The age stratification in the
society will disappear, and along with it,
many of our current social mores. The new
ideas and new possibilities will evolve.
Vinod Nikhra, M.D.
www.vinodnikhra.com
www.nikhrafoundation.in