Sunday, April 6, 2014

Monkeying Around With Longevity

The search to extend human longevity spans the ages. More recently, scientists have repeatedly shown that restricting the intake of calories while continuing to supply essential nutrients extends the lifespan of flies and yeast by as much as 40 percent. An additional research vector that captured much attention were animal studies with rodents that suggested similar benefits from caloric restriction. 

Although positive results were not seen with all strains of rodents, some rodents were shown to live significantly longer when their calories were limited.  As with all animal studies, scientists wanted to know if these benefits extended to more complex creatures that more closely resemble humans--such as primates--better known as monkeys.

When the National Institute of Aging (NIA) completed their studies with monkeys in 2012, the NIA's conclusion was that that caloric restriction made no difference. This hardly put the controversy to bed, but it did seem to dampen some enthusiasm for this approach to extending human longevity.

This past week, a new study from the University of Wisconsin stirs up new hope for reconsidering this strategy. Over 25 years, Wisconsin researchers studying rhesus monkeys, considered by some the best proxies for humans, found a significant reduction in mortality and in age-associated diseases among those monkeys fed calorie-restricted diets. The study, begun at the University of Wisconsin-Madison in 1989, is one of two ongoing, long-term U.S. efforts to examine the effects of a reduced-calorie diet on nonhuman primates.

The study of 76 rhesus monkeys, reported Monday in Nature Communications, was performed at the Wisconsin National Primate Research Center in Madison. When the monkeys were 7 to 14 years of age, they began eating a diet reduced in calories by 30 percent. The comparison monkeys, or the control group, which ate as much as they wanted, had an increased risk of disease 2.9 times that of the calorie-restricted group, and a threefold increased risk of death.

So which study is correct?  According to the Wisconsin researchers the reason for the discrepant results is that the NIA monkeys that were in the control group versus the intervention group were actually already on calorie restricted diets and that's why no difference was found in longevity between the two groups. Also, the NIA monkeys were consistently slimmer (and presumably healthier) that the Wisconsin monkeys, who were allowed to eat what they wanted. (I guess even monkeys, particularly captive ones, overeat when enabled to do so.) The NIA was apparently more careful with all their monkeys to limit their food intake regardless of the study.

How did the Wisconsin researchers reach this conclusion? Through their own experience in monkey research, and by reference to an online database recording the weight of thousands of research monkeys, the Wisconsin researchers concluded that the NIA controls were actually on caloric restriction as well. “At all the time points that have been published by NIA, their control monkeys weigh less than ours, and in most cases, significantly so” stated Ricki Colman, a senior scientist at the Wisconsin Primate Center, who presently co-leads the project.

More importantly, the NIA control group monkeys were also found to live longer on average that most other monkeys, and the Wisconsin researchers theorized that this was due to even a small reduction of calories. The big conclusion was that it seems that the small caloric restriction in the NIA control animals had its own benefits, suggesting that a reduction of as little as 10 percent could meaningfully retard aging.

As these studies were very expensive to conduct and will therefore not be repeated any time soon, the question remains do primates benefit from calorie restriction as long as they get all essential nutrients? The Wisconsin study would suggest that for rhesus monkeys, the answer is yes.

So what does that mean for us humans?

According to the Wisconsin researchers, they were“not studying [caloric restriction]...so people can go out and do it, but [rather] to delve into the underlying causes of age-related disease susceptibility...It’s a research tool, not a lifestyle recommendation."

Although the helpful mechanism of why caloric restriction may be beneficial has not been fully identified, it is believed to have something to do with the "reprogramming of the metabolism. In all species where it has been shown to delay aging and the diseases of aging, [calories restriction]... affects the regulation of energy and the ability of cells and the organism to respond to changes in the environment as they age.”

One of the first break-downs in metabolism results in diabetes, which can be seen as “an inability to properly respond to nutrients.” Diabetes damages a whole range of human capabilities including the functioning of muscle, fat and blood vessels. "The Wisconsin scientists began to see diabetes among the control animals while they were still in the prime of life, within six months after beginning their study. The contrast with the restricted animals could not have been more dramatic" Colman said. “Until two years ago, we did not have evidence of diabetes in any caloric-restriction animal, but we had a significant number of diabetes, or pre-diabetes, metabolic syndrome, in the control animals.”

Although it is generally accepted that very few people can tolerate a 30 percent reduction in calories, the study does merit consideration.  Primarily because “the basic biology of caloric restriction in rodents, worms, flies and yeast seems to carry over to primates," it appears worthwhile to identify the underlying mechanism for this result in order to better understand the potential benefit to human primates who are genetically so closely related to rhesus monkeys.

The bottom line here is that as long as they all get their essential nutrients it would appear across multiple species, from simple worms to far more complex primates, that eating less is better than eating more. It's not a large stretch to extend that logic to homo sapiens. Accordingly, even cutting back on 10% of your calories may have a huge effect on your longevity--adding years of healthy living to your life.  And that's not something to monkey around with.


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