How can we make sense of the disparate results from the four primate studies on caloric restriction and lifespan?
Diet and Caloric Restriction for Longevity—The Monkey Trials
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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Calorie restriction in primates to extend lifespan. Will it work? There’s only one way to find out. There have been four investigations of calorie restriction and lifespan in nonhuman primates. The first was published in 2003, an analysis of the mortality of 117 rhesus monkeys followed for about 25 years in a lab, eight of whom had their Purina monkey chow restricted. The average survival of the restricted monkeys was to 32 years of age, compared to 25 years for the control monkeys. However, it was more of an observational study, since the monkeys weren’t randomly assigned. And, although in the abstract, they talk about the survival advantage and how the ad libitum monkeys—the eat-all-you-want monkeys—had more than twice the risk of death, they acknowledge deeper in the paper that the difference in death did not reach statistical significance––meaning it may have very well been a fluke. That was all we had, though, until results started trickling in from the famous pair of studies that involved randomizing about 200 rhesus monkeys to caloric restriction or more normal diets––one out of the University of Wisconsin—Madison (UW), and another from the National Institute of Aging (NIA).
The UW study reported a 30 percent caloric restriction significantly delayed disease and improved survival, but the NIA study did not. In the UW study, caloric restriction reduced the incidence of age-related diseases including cancer, cardiovascular disease, brain atrophy, and muscle wasting, preserving muscle mass––demonstrating caloric restriction can delay aging. But in the NIA study, the difference in age-related diseases did not achieve statistical significance. In the UW study, the restricted monkeys lived to an average of about 29 years compared to the control monkeys, who lived closer to the average for monkeys in captivity of about 26 years old. In contrast, though one of the restricted monkeys in the NIA study became the longevity record holder for the species at age 43, on average, the restricted group didn’t live any longer than the control animals. Why the disparate results between the two studies?
In the NIA study that found no significant lifespan difference, the control group was not fed ad libitum, but rather had food portioned out to prevent excess weight gain. In contrast, in the UW study, the control monkeys could eat as much as they wanted throughout the day, so ended up weighing more than the NIA control animals. Of course, caloric restriction would improve the health and survival of overweight monkeys, just as weight loss would be beneficial for overweight people. But the null results in the NIA study suggest that normal-weight people might not benefit from restricting further.
The NIA monkeys were also fed a healthier diet. The diet in the UW study, where they saw significant benefit to cutting down, was an ultra-processed concoction of largely milk protein, corn oil, corn starch, and table sugar, whereas the NIA diet actually included unprocessed plant foods such corn, soybeans, and wheat, and so actually had some phytonutrients. About 29 percent of the UW diet was straight sugar, compared to 4 percent in the NIA diet. (American adults get about 17 teaspoons of sugar a day, which is about 13 percent of calories.) The contrasting findings suggest that the worse your diet is, the more important it is to eat less of it.
The fourth study was on grey mouse lemurs, among the smallest of primates, standing just three inches tall. Those randomized to a 30 percent caloric restriction compared to the ad libitum control group lived a whopping 50 percent longer. And not just average lifespan, but maximal lifespan. The maximum lifespan was boosted by about 20 percent. However, the “calorie restricted” group still weighed heavier than their wild counterparts; so again, this may just be an illustration of the harms of obesity and another indictment against all-you-can-eat buffets. Also, those in the calorie restriction group experienced an acceleration of age-related loss of grey matter throughout their brains, though this did not appear to translate into cognitive or behavioral differences.
Pooling the three rhesus monkey studies together, there seemed to be lower age-related mortality, but no significant difference in average lifespans overall between the caloric restriction groups and the control groups. Given the time and expense, there is little chance we are going to see any more long-term primate studies on caloric restriction for life extension. So, what can we draw from the primate data to date? If you’re overweight or living off junk food, eating less is a good idea.
Please consider volunteering to help out on the site.
- Bodkin NL, Alexander TM, Ortmeyer HK, Johnson E, Hansen BC. Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J Gerontol A Biol Sci Med Sci. 2003;58(3):212-219.
- Lane MA, Mattison JA, Roth GS, Brant LJ, Ingram DK. Effects of long-term diet restriction on aging and longevity in primates remain uncertain. J Gerontol A Biol Sci Med Sci. 2004;59(5):B405-7.
- Colman RJ, Anderson RM, Johnson SC, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325(5937):201-204.
- Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun. 2014;5(1):3557.
- Mattison JA, Roth GS, Beasley TM, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012;489(7415):318-21.
- Colman RJ, Beasley MT, Allison DB, Weindruch R. Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J Gerontol A Biol Sci Med Sci. 2008;63(6):556-9.
- Mattison JA, Colman RJ, Beasley TM, et al. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017;8:14063.
- Le Bourg E. Does calorie restriction in primates increase lifespan? Revisiting studies on macaques (Macaca mulatta) and mouse lemurs (Microcebus murinus). Bioessays. 2018;40(10):e1800111.
- Mendelsohn AR, Larrick JW. Dietary restriction: critical co-factors to separate health span from life span benefits. Rejuvenation Res. 2012;15(5):523-529.
- Wolf AM. Rodent diet aids and the fallacy of caloric restriction. Mech Ageing Dev. 2021;200:111584.
- Wiggins T, Guidozzi N, Welbourn R, Ahmed AR, Markar SR. Association of bariatric surgery with all-cause mortality and incidence of obesity-related disease at a population level: a systematic review and meta-analysis. PLoS Med. 2020;17(7):e1003206.
- Vaughan KL, Kaiser T, Peaden R, Anson RM, de Cabo R, Mattison JA. Caloric restriction study design limitations in rodent and nonhuman primate studies. J Gerontol A Biol Sci Med Sci. 2017;73(1):48-53.
- Food Patterns Equivalents Intakes from Food: Mean Amounts Consumed per Individual, by Gender and Age, What We Eat in America, NHANES 2017-2018. USDA. 2020.
- Energy Intakes: Percentages of Energy from Protein, Carbohydrate, Fat, and Alcohol, by Gender and Age, What We Eatin America, NHANES 2017-2018. USDA. 2020.
- Pifferi F, Terrien J, Marchal J, et al. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. Commun Biol. 2018;1:30.
- Pifferi F, Terrien J, Perret M, et al. Promoting healthspan and lifespan with caloric restriction in primates. Commun Biol. 2019;2:107.
- Hultström M. Caloric restriction reduces age-related but not all-cause mortality. Acta Physiol (Oxf). 2015;214(1):3-5.
- Le Bourg E. Is it time to state that diet restriction does not increase life span in primates? J Gerontol A Biol Sci Med Sci. 2018;73(3):308-309.
- Roth GS, Ingram DK, Lane MA. Calorie restriction in primates: will it work and how will we know? J Am Geriatr Soc. 1999;47(7):896-903.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Calorie restriction in primates to extend lifespan. Will it work? There’s only one way to find out. There have been four investigations of calorie restriction and lifespan in nonhuman primates. The first was published in 2003, an analysis of the mortality of 117 rhesus monkeys followed for about 25 years in a lab, eight of whom had their Purina monkey chow restricted. The average survival of the restricted monkeys was to 32 years of age, compared to 25 years for the control monkeys. However, it was more of an observational study, since the monkeys weren’t randomly assigned. And, although in the abstract, they talk about the survival advantage and how the ad libitum monkeys—the eat-all-you-want monkeys—had more than twice the risk of death, they acknowledge deeper in the paper that the difference in death did not reach statistical significance––meaning it may have very well been a fluke. That was all we had, though, until results started trickling in from the famous pair of studies that involved randomizing about 200 rhesus monkeys to caloric restriction or more normal diets––one out of the University of Wisconsin—Madison (UW), and another from the National Institute of Aging (NIA).
The UW study reported a 30 percent caloric restriction significantly delayed disease and improved survival, but the NIA study did not. In the UW study, caloric restriction reduced the incidence of age-related diseases including cancer, cardiovascular disease, brain atrophy, and muscle wasting, preserving muscle mass––demonstrating caloric restriction can delay aging. But in the NIA study, the difference in age-related diseases did not achieve statistical significance. In the UW study, the restricted monkeys lived to an average of about 29 years compared to the control monkeys, who lived closer to the average for monkeys in captivity of about 26 years old. In contrast, though one of the restricted monkeys in the NIA study became the longevity record holder for the species at age 43, on average, the restricted group didn’t live any longer than the control animals. Why the disparate results between the two studies?
In the NIA study that found no significant lifespan difference, the control group was not fed ad libitum, but rather had food portioned out to prevent excess weight gain. In contrast, in the UW study, the control monkeys could eat as much as they wanted throughout the day, so ended up weighing more than the NIA control animals. Of course, caloric restriction would improve the health and survival of overweight monkeys, just as weight loss would be beneficial for overweight people. But the null results in the NIA study suggest that normal-weight people might not benefit from restricting further.
The NIA monkeys were also fed a healthier diet. The diet in the UW study, where they saw significant benefit to cutting down, was an ultra-processed concoction of largely milk protein, corn oil, corn starch, and table sugar, whereas the NIA diet actually included unprocessed plant foods such corn, soybeans, and wheat, and so actually had some phytonutrients. About 29 percent of the UW diet was straight sugar, compared to 4 percent in the NIA diet. (American adults get about 17 teaspoons of sugar a day, which is about 13 percent of calories.) The contrasting findings suggest that the worse your diet is, the more important it is to eat less of it.
The fourth study was on grey mouse lemurs, among the smallest of primates, standing just three inches tall. Those randomized to a 30 percent caloric restriction compared to the ad libitum control group lived a whopping 50 percent longer. And not just average lifespan, but maximal lifespan. The maximum lifespan was boosted by about 20 percent. However, the “calorie restricted” group still weighed heavier than their wild counterparts; so again, this may just be an illustration of the harms of obesity and another indictment against all-you-can-eat buffets. Also, those in the calorie restriction group experienced an acceleration of age-related loss of grey matter throughout their brains, though this did not appear to translate into cognitive or behavioral differences.
Pooling the three rhesus monkey studies together, there seemed to be lower age-related mortality, but no significant difference in average lifespans overall between the caloric restriction groups and the control groups. Given the time and expense, there is little chance we are going to see any more long-term primate studies on caloric restriction for life extension. So, what can we draw from the primate data to date? If you’re overweight or living off junk food, eating less is a good idea.
Please consider volunteering to help out on the site.
- Bodkin NL, Alexander TM, Ortmeyer HK, Johnson E, Hansen BC. Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J Gerontol A Biol Sci Med Sci. 2003;58(3):212-219.
- Lane MA, Mattison JA, Roth GS, Brant LJ, Ingram DK. Effects of long-term diet restriction on aging and longevity in primates remain uncertain. J Gerontol A Biol Sci Med Sci. 2004;59(5):B405-7.
- Colman RJ, Anderson RM, Johnson SC, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325(5937):201-204.
- Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun. 2014;5(1):3557.
- Mattison JA, Roth GS, Beasley TM, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012;489(7415):318-21.
- Colman RJ, Beasley MT, Allison DB, Weindruch R. Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J Gerontol A Biol Sci Med Sci. 2008;63(6):556-9.
- Mattison JA, Colman RJ, Beasley TM, et al. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017;8:14063.
- Le Bourg E. Does calorie restriction in primates increase lifespan? Revisiting studies on macaques (Macaca mulatta) and mouse lemurs (Microcebus murinus). Bioessays. 2018;40(10):e1800111.
- Mendelsohn AR, Larrick JW. Dietary restriction: critical co-factors to separate health span from life span benefits. Rejuvenation Res. 2012;15(5):523-529.
- Wolf AM. Rodent diet aids and the fallacy of caloric restriction. Mech Ageing Dev. 2021;200:111584.
- Wiggins T, Guidozzi N, Welbourn R, Ahmed AR, Markar SR. Association of bariatric surgery with all-cause mortality and incidence of obesity-related disease at a population level: a systematic review and meta-analysis. PLoS Med. 2020;17(7):e1003206.
- Vaughan KL, Kaiser T, Peaden R, Anson RM, de Cabo R, Mattison JA. Caloric restriction study design limitations in rodent and nonhuman primate studies. J Gerontol A Biol Sci Med Sci. 2017;73(1):48-53.
- Food Patterns Equivalents Intakes from Food: Mean Amounts Consumed per Individual, by Gender and Age, What We Eat in America, NHANES 2017-2018. USDA. 2020.
- Energy Intakes: Percentages of Energy from Protein, Carbohydrate, Fat, and Alcohol, by Gender and Age, What We Eatin America, NHANES 2017-2018. USDA. 2020.
- Pifferi F, Terrien J, Marchal J, et al. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. Commun Biol. 2018;1:30.
- Pifferi F, Terrien J, Perret M, et al. Promoting healthspan and lifespan with caloric restriction in primates. Commun Biol. 2019;2:107.
- Hultström M. Caloric restriction reduces age-related but not all-cause mortality. Acta Physiol (Oxf). 2015;214(1):3-5.
- Le Bourg E. Is it time to state that diet restriction does not increase life span in primates? J Gerontol A Biol Sci Med Sci. 2018;73(3):308-309.
- Roth GS, Ingram DK, Lane MA. Calorie restriction in primates: will it work and how will we know? J Am Geriatr Soc. 1999;47(7):896-903.
Motion graphics by Avo Media
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Diet and Caloric Restriction for Longevity—The Monkey Trials
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Content URLDoctor's Note
Here are some of my previous videos on dietary restriction if you’re interested in taking a deeper dive:
- The Benefits of Caloric Restriction Without the Actual Restricting
- Caloric Restriction vs. Animal Protein Restriction
- Caloric Restriction vs. Plant-Based Diets
- The Benefits of Calorie Restriction for Longevity
- Potential Pitfalls of Calorie Restriction
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