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  • Tuesday, April 3, 2007

    Thoughts on Calorie Restriction Research

    Scientists are chewing over the past year of advances in calorie restriction and calorie restriction mimetic research, as indicated by a couple of recent papers on the subject.

    Vertebrate aging research 2006:

    The year's highlights include studies of oxidation damage in the very-long-lived naked mole-rat, and of caloric restriction in monkeys, humans, and growth hormone-unresponsive mice. Two studies of resveratrol, one showing its ability to extend lifespan in a short-lived fish, the other demonstrating beneficial effects in mice subjected to a diet high in fat, may well be harbingers of a parade of intervention studies in the coming decade.

    Starving for Life: What Animal Studies Can and Cannot Tell Us about the Use of Caloric Restriction to Prolong Human Lifespan:

    Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

    "Starving" is over the top - even scientists are vulnerable to the urge for a better headline, it seems. Calorie restriction is anything but starvation, given the focus on optimal nutrition - and it's only infeasible if you're disinterested in looking after your health.

    Still, some interesting points are raised, especially the idea that hunger might play a role in the regulatory mechanics that produce beneficial effects in our biochemistry. I can see that proposition spurring debate amongst the members of the Calorie Restriction Society, given the very different levels of self-reported hunger and various methodologies for managing it.

    It's nice to see a researcher planting a flag in the map on the degree to which calorie restriction will extend human life span; all too few folk are willing to do that in public. It's interesting that those who do so tend to be the skeptics - not skeptical that it will work, but skeptical that calorie restriction will provide more than a couple of extra years of life in humans. Which is a couple of extra years of life on top of avoiding most of the common age-related illnesses, and generally being exceptionally healthy in old age, if the human studies continue to hold up.

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