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Metabolism & Nutrition – Tutorial 1: Caloric restriction (CR)

For the 2015 Metabolism & Nutrition course at the RuG, I’m asked to read two papers on two parralel studies on increased longevity of rhesus monkeys (Macaca mulatta) through caloric restriction (CR). Colman et al. (2014) report a positive effect of caloric restriction on longevity for the study at the Wisconsin National Primate Research Center (WNPRC), but these effects could not be confirmed by Mattison et al. (2012), with macaques kept at the US National Institute on Aging (NIA).

I was first introduced to this subject in 2009, in a Wired article on previous results (Colman et al., 2009) from the WNPRC research group. When these results came out, they seemed to confirm what had often been demonstrated for short-lived animal species and even fungi: that CR can increase longevity and delay the onset of age-related disease. In fact, since these effects were first found in rats and mice in the mid-1930s, many people have been practicing caloric restriction in hope of extending their (youthful) life. Mice are short-lived animals, however, with life histories very much unlike those of long-lived primates such as ourselves, which is why the experiments on macaque monkeys were initiated, in 1987 at the NIA, and in 1989 at the WNPRC.

Although early (2009) results of the WNPRC group were promising, the NIA results show less significant benefits from CR. Colman et al. (2014) assigned the failure to of the NIA experiment to replicate their (WNPRC’s) positive results to differences in experimental design. Contrary to the control group in the WNPRC experiment, the NIA control monkeys were not fed ad libitum. Also, there were differences in the composition of the control and CR diets between both experiments. Austad (2012) clearly lays out these contradictory results and offers some possible explanations.

As for now, it is difficult to say if CR will extend the average life-span of primates. And if it does increase longevity in some, it is important to consider genetic variation that may affect the effects of CR. Austad and colleagues previously found that the offspring of wild mice did not profit from CR as their lab-bred conspecifics did (Harper et al., 2006). Incidentally, he wonders: “Is calorie restriction anything more than the elimination of excess fat?” (Austad, 2012). In other words: are the CR monkeys healthier, because they weigh less?

As for me, I know that a healthy lifestyle may help you to stay healthy until you’re about seventy or eighty years old. But, people who live to be ninety-five or older don’t live healthier than average lifestyles (Rajpathak, 2011). My longest-surviving grandfather died at ninety-four, not quite ninety-five. It could be a bit of a gamble, but I’m not going to torture myself with a 10–30% reduction in calories, not as long as my phenotype includes an eight-pack (and that’s on a high-fat, high-protein, high-carb diet).

References

Austad, Steven N. “Ageing: Mixed results for dieting monkeys.” Nature (2012).

Colman, Ricki J., Rozalyn M. Anderson, Sterling C. Johnson, Erik K. Kastman, Kristopher J. Kosmatka, T. Mark Beasley, David B. Allison et al. “Caloric restriction delays disease onset and mortality in rhesus monkeys.” Science 325, no. 5937 (2009): 201-204.

Colman, Ricki J., T. Mark Beasley, Joseph W. Kemnitz, Sterling C. Johnson, Richard Weindruch, and Rozalyn M. Anderson. “Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys.” Nature communications 5 (2014).

Harper, James M., Charles W. Leathers, and Steven N. Austad. “Does caloric restriction extend life in wild mice?.” Aging cell 5, no. 6 (2006): 441-449.

Mattison, Julie A., George S. Roth, T. Mark Beasley, Edward M. Tilmont, April M. Handy, Richard L. Herbert, Dan L. Longo et al. “Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.” Nature (2012).

Rajpathak, Swapnil N., Yingheng Liu, Orit Ben‐David, Saritha Reddy, Gil Atzmon, Jill Crandall, and Nir Barzilai. “Lifestyle factors of people with exceptional longevity.” Journal of the American Geriatrics Society 59, no. 8 (2011): 1509-1512.


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