Saturday, January 31, 2009

Human lifespan may not be easily extended

There’s been some guarded optimism among scientists that it might be possible to find drugs that slow human aging, and either extend lifespan (slow aging does not extend lifespan if you die young of cancer) or compress debility. A contrary opinion is that most humans operate near the limit of our biology, and that lifespan is largely randomly determined.

The reference for most of the drug studies are the known lifespan extending effects of caloric restriction. Known, that is, in worms, flies, some monkeys, and rodents.

Alas for the guarded optimists, caloric restriction may only work for humans who are fat (emphases mine) …

Restricting calories may not extend lifespan for everyone: Scientific American Blog

Scientists have long known that severely cutting food intake may lead to a longer life. But new research shows the phenom doesn't apply to everyone – or, should we say, to every mouse. A new study recently published in the online edition of the Journal of Nutrition found that reducing caloric intake only seems to prolong the lives of fat mice with low metabolisms.

"There has been this kind of settled paradigm that caloric restriction universally extends the life span of animals, [and] some have implied that it also applies to humans," says study lead author Rajindar Sohal, a pharmacologist at the University of Southern California in Los Angles. But he notes that he and his colleagues found that "extension of lifespan by food reduction will occur only if there is an energy imbalance [caused by a low metabolism]."

Scientists have known for more than 70 years that slashing caloric intake by an average of 30 percent to 40 percent extends the lives of animals as diverse as rodents and monkeys. But this effect is not seen across the board, according to Sohal. Some breeds of mice, for example, live 25 to 30 percent longer when their caloric intake is cut by 40 percent, while other breeds experience no benefit from shrinking calories.

Suspecting that metabolism (the speed at which calories are burned) might explain the discrepancy, the researchers compared the metabolic rates of two strains of mice: C57BL/6 mice, which are known to enjoy the life-extending effects of dieting, and DBA/2 mice, for whom dieting has been found to have no effect on life span. They found that C57BL/6 mice had much lower metabolisms than the DBA/2 mice, regardless of how much they consumed. C57BL/6 were also, on average, beefier. 

These findings suggest that calorie restriction does not have the same effect on every animal. In other words, going on diet won't prolong the lives of mice with high metabolisms (who are likely to be thin, anyway), but it could help obese mice with low metabolisms. Sohal speculates that humans will respond the same way, but notes that such studies aren't practical in people. "You can't put human [study subjects] on caloric restrictions all their lives," he says, but adds: "There is no reason why it couldn't apply to humans."

The next step is pinpointing the cause of these metabolic differences, Sohal says: "What I would like to know is, what are the specific genes that determine the difference in metabolic rate?"

Human obesity is associated with shortened life spans. So it may be that “beefy” humans will benefit from, say, Resveratrol, while skinny humans will not. One might even imagine that slow metabolizers who manage to stay thin will tend to age slowly and live longer.

Or not.

There’s a lot of marvelous science to be done, but investments in Sirtuin drugs remains highly speculative. Techo-optimists should not book their tickets to the 22nd century Singularity.

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