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March 2006

The Fountain of Health

Antiaging researchers could provide a powerful approach to treating the many diseases of old age.

By David Rotman

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For the better part of two decades, Richard Weindruch, a professor of medicine at the University of Wisconsin-Madison, has fed half of a colony of 78 rhesus monkeys a diet adequate in nutrition but severely limited in calories -- 30 percent fewer calories than are fed to the control group. Scientists have known for nearly 70 years that such calorie restriction extends the life span of rodents, and Weindruch is determined to find out whether it can extend the life span of one of man's closest relatives, too.

It's too early to know the answer for certain. The monkeys in Weindruch's lab are only now growing elderly. And with 80 percent of them still alive, "there are too few deaths" to indicate whether the animals on the restricted diet will live longer, says Weindruch. But one thing is already clear: the monkeys on the restricted diet are healthier. Roughly twice as many of the monkeys in the control group have died from age-related diseases, and perhaps most dramatically, none of the animals on the restricted diet have developed diabetes, a leading cause of death in rhesus monkeys.

These encouraging, albeit preliminary, results are sure to cheer those few who have adopted severe calorie-restricted diets in hopes of living longer. But their real significance is the further evidence they provide that calorie restriction affects the molecular and genetic events that govern aging and the diseases of aging. Indeed, while calorie restriction remains impractical for all but the most determined dieters, it is providing an invaluable window on the molecular and cellular biology of disease resistance and the aging process.

Up until a decade or so ago, most biologists believed that the aging process was not only immensely complex but also inevitable. People aged, they assumed, much the way an old car does: eventually, everything just falls apart. Then in the early 1990s, Cynthia Kenyon, a young molecular biologist at the University of California, San Francisco, found that mutating a single gene, called daf-2, in worms doubled their life spans. Before the discovery, says Kenyon, "everyone thought aging just happened. To control aging, you had to fix everything, so it was impossible." Kenyon's research suggested a compelling alternative: that a relatively simple genetic network controlled the rate of aging.

The race to find the genetic fountain of youth was on. Within a few years, Leonard Guarente, a biologist at MIT, found that in yeast, another gene produced a similar dramatic increase in life span. Soon after, Guarente and his MIT coworkers made another startling discovery: the yeast antiaging gene, called sir2, required for its activity a common molecule that is involved in numerous metabolic reactions. Guarente, it seemed, had found a possible connection between an antiaging gene and diet. The gene, Guarente thought, might be responsible for the health benefits of calorie restriction; and indeed, the lab soon confirmed that calorie restriction in yeast had life-extending effects only when sir2 was present.

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March/April 2006

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Comments

  • Metabolism and perception of time
    Guest (Jeremy Villalobos) on 03/23/2006 at 12:00 AM
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    1
    One question that this article leave me asking, If you lower the metabolism of an organism, does that have an effect on how that organism perceives time?  If so, I guess I would not like to live longer if everything around me start to progress faster.
    Rate this comment: 12345
  • Sirtuin
    Guest (James R Hughes, MD) on 04/06/2006 at 12:00 AM
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    1
    Great write up.  There is also evidence the chemicals in the family of Resveritrol also increase SIR2 expression.  I think, at present, the best longevity regime for humans is every other day fasting (40% calorie restriction), exercising on fasting days (to promote lipolysis/gluconeogenesis pathways) and a good glass of red wine daily (high resveritrol content). I've been doing this over a year and feel better than I ever have and haven't got sick once.  There are many other pathways the fasting stimulates, and is doesn't make you "hungry all the time" like pure calorie restriction.
    Rate this comment: 12345
    • The longer candle.
      Guest (Steve Koelzer) on 04/10/2006 at 12:00 AM
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      1
      Great article and comments.  As a lifetime (chemist) researcher I take great pleasure absorbing info.  Doing something other than appreciating knowledge requires keeping it in mind and retrieving it, so as to not falter or repeat mistakes.  To that end I figured out early that memory must take precedence.  Unfortunately drugs won’t work as well as natural methods, one of which is FOOD.  As information became available over decades, by adopting ortho-dietetic chemistry the value of managing free radicals became old hat.  As I focused on brain optimization it turned out that while preparing a 2005 Centigenarian address on dietarily enhancing IL-10 and minimizing IL-6 I discovered I had already adopted the two major factors.  I began taking selenium in 1973 and omega three oils in 1983. 
      Rate this comment: 12345
      • Longer candle (ct'd).
        Guest (Steve Koelzer) on 04/10/2006 at 12:00 AM
        Posts:
        1
        Thus mentation and longevity go hand in hand.  Yes, rodents eating ad lib. semi-daily benefit as well or better than those calorie restricted.  Yes, taking antioxidants can help (a little) but first one should ensure getting the right amounts of each and every essential and indispensable nutrient.  As for resveratrol and flavonoids I have not moved to the purified sources yet but do chew dark grapes like a cud and go after Spanish sage and shallots, to name a few.  I avoid every foodstuff I’ve learned is not good and even breathed air slowly to filter it better.  I’m not yet 60 and my mind feels a teenager.  Hope this helps.  PS No alcohol for 20 years!
        Rate this comment: 12345
    • Mitochondria
      Guest (Bill Jackson) on 05/04/2006 at 12:00 AM
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      1
      We have heard comments that there are two mechanisms that seem to limit cellular longevity.
      One is the telomere length that is reduced bit by bit until the cell can no longer divide. Another is the gradual loss of the energy provisioning abilities of the mitochondria, which seem to act to limit cellular activity with advanced age.

      If one transplanted some intact mitochondria from a long lived species into a short lived one, what would happen? Would the organism last longer? I suggest this be done first on related species with well known but short disparate lifetimes so the effect, if any, would be seen quickly.
      Rate this comment: 12345
      • Mitochondria
        Guest (Diane Ritter) on 08/03/2006 at 12:00 AM
        Posts:
        1
        What an interesting idea.  I hope somebody picks up on this and tries it. 
        Rate this comment: 12345
  • curing disease vs. life-extension
    Guest (John Schloendorn) on 04/26/2006 at 12:00 AM
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    1
    The summary of this article goes "Antiaging researchers aren’t likely to find ways to extend life anytime soon. But their work could provide a powerful approach to treating the many diseases of old age."

    I wonder how the author of this summary thinks a (presumably successful) treatment of age-related diseases can avoid resulting in life-extension... If we cure or postpone age-related diseases, i.e. things that kill us in old-age, then will we not almost by definition live longer?
    Rate this comment: 12345
    • Re: curing disease vs. life-extension
      rbarkley373 on 09/17/2007 at 2:36 AM
      Posts:
      1
      Yes and no. Curing diseases will increase the average lifespan (and could extend your life dramatically) but not have a significant effect on the maximum life span. It is increasing the maximum that is the goal of "life-extension".
      Rate this comment: 12345
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