Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study

Abstract

Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function1,2, motor coordination3 and resistance to sarcopenia4 in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years)5 and a preliminary report with a small number of CR monkeys6. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents7,8,9, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Survival curve and triglycerides, cholesterol and glucose levels for old-onset monkeys.
Figure 2: Survival curves and glucose and triglycerides levels for young-onset monkeys.
Figure 3: Incidence and estimated proportions of age-related diseases.

Similar content being viewed by others

References

  1. Branch-Mays, G. L. et al. The effects of a calorie-reduced diet on periodontal inflammation and disease in a non-human primate model. J. Periodontol. 79, 1184–1191 (2008)

    Article  Google Scholar 

  2. Messaoudi, I. et al. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates. Proc. Natl Acad. Sci. USA 103, 19448–19453 (2006)

    Article  ADS  CAS  Google Scholar 

  3. Kastman, E. K. et al. A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys. J. Neurosci. 30, 7940–7947 (2010)

    Article  CAS  Google Scholar 

  4. Colman, R. J., Beasley, T. M., Allison, D. B. & Weindruch, R. Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J. Gerontol. A 63, 556–559 (2008)

    Article  Google Scholar 

  5. Colman, R. J. et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204 (2009)

    Article  ADS  CAS  Google Scholar 

  6. Bodkin, N. L., Alexander, T. M., Ortmeyer, H. K., Johnson, E. & Hansen, B. C. Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. J. Gerontol. A 58, B212–B219 (2003)

    Article  Google Scholar 

  7. Forster, M. J., Morris, P. & Sohal, R. S. Genotype and age influence the effect of caloric intake on mortality in mice. FASEB J. 17, 690–692 (2003)

    Article  Google Scholar 

  8. Murtagh-Mark, C. M., Reiser, K. M., Harris, R., Jr & McDonald, R. B. Source of dietary carbohydrate affects life span of Fischer 344 rats independent of caloric restriction. J. Gerontol. A 50A, B148–B154 (1995)

    Article  CAS  Google Scholar 

  9. Swindell, W. R. Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan. Ageing Res. Rev. 11, 254–270 (2012)

    Article  Google Scholar 

  10. Messaoudi, I. et al. in Calorie Restriction, Aging, and Longevity (eds Everitt, A. V., Rattan, S., Le Couteur, D. & de Cabo, R. ) 55–78 (Springer, 2010)

  11. Roth, G. S. et al. Aging in rhesus monkeys: relevance to human health interventions. Science 305, 1423–1426 (2004)

    Article  ADS  CAS  Google Scholar 

  12. Ingram, D. K. et al. Dietary restriction and aging: the initiation of a primate study. J. Gerontol. 45, B148–B163 (1990)

    Article  CAS  Google Scholar 

  13. Mattison, J. A. et al. Age-related decline in caloric intake and motivation for food in rhesus monkeys. Neurobiol. Aging 26, 1117–1127 (2005)

    Article  Google Scholar 

  14. Colman, R. J. & Kemnitz, J. W. in Methods in Aging Research (ed. Yu, B. P. ) 249–267 (CRC, 1998)

    Book  Google Scholar 

  15. Messaoudi, I. et al. Optimal window of caloric restriction onset limits its beneficial impact on T-cell senescence in primates. Aging Cell 7, 908–919 (2008)

    Article  CAS  Google Scholar 

  16. Allison, P. D. Survival Analysis Using SAS: A Practical Guide (SAS Institute, 1995)

    Google Scholar 

  17. Nadon, N. L. Exploiting the rodent model for studies on the pharmacology of lifespan extension. Aging Cell 5, 9–15 (2006)

    Article  CAS  Google Scholar 

  18. Lomba, A. et al. A high-sucrose isocaloric pair-fed model induces obesity and impairs NDUFB6 gene function in rat adipose tissue. J. Nutrigenet. Nutrigenomics 2, 267–272 (2009)

    Article  CAS  Google Scholar 

  19. Roncal-Jimenez, C. A. et al. Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake. Metabolism 60, 1259–1270 (2011)

    Article  CAS  Google Scholar 

  20. Duffy, P. H. et al. The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies. Aging (Milano) 13, 263–272 (2001)

    CAS  Google Scholar 

  21. Raman, A. et al. Influences of calorie restriction and age on energy expenditure in the rhesus monkey. Am. J. Physiol. Endocrinol. Metab. 292, E101–E106 (2007)

    Article  CAS  Google Scholar 

  22. Liao, C. Y., Rikke, B. A., Johnson, T. E., Diaz, V. & Nelson, J. F. Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell 9, 92–95 (2010)

    Article  CAS  Google Scholar 

  23. Harper, J. M., Leathers, C. W. & Austad, S. N. Does caloric restriction extend life in wild mice? Aging Cell 5, 441–449 (2006)

    Article  CAS  Google Scholar 

  24. Speakman, J. R. & Hambly, C. Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan. J. Nutr. 137, 1078–1086 (2007)

    Article  CAS  Google Scholar 

  25. Roth, G. S. et al. Age-related changes in androgen levels of rhesus monkeys subjected to diet restriction. Endocr. J. 1, 227–234 (1993)

    Google Scholar 

  26. Lane, M. A. et al. Aging and food restriction alter some indices of bone metabolism in male rhesus monkeys (Macaca mulatta). J. Nutr. 125, 1600–1610 (1995)

    CAS  PubMed  Google Scholar 

  27. Redman, L. M. & Ravussin, E. Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxid. Redox Signal. 14, 275–287 (2011)

    Article  CAS  Google Scholar 

  28. Omodei, D. & Fontana, L. Calorie restriction and prevention of age-associated chronic disease. FEBS Lett. 585, 1537–1542 (2011)

    Article  CAS  Google Scholar 

  29. Ward, W. F. et al. Effects of age and caloric restriction on lipid peroxidation: measurement of oxidative stress by F2-isoprostane levels. J. Gerontol. A 60, 847–851 (2005)

    Article  Google Scholar 

  30. Littell, R. C., Milliken, G. A., Stroup, W. W., Wolfinger, R. D. & Schabenberger, O. SAS for Mixed Models (SAS Institute Inc., 2006)

Download references

Acknowledgements

We thank the animal care staff and technicians, both past and present, especially J. Travis and M. Szarowicz; K. Vaughan for her editorial help; and the many collaborators that have contributed to this project. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging.

Author information

Authors and Affiliations

Authors

Contributions

G.S.R. and D.K.I. jointly conceived the original study and implemented it. J.A.M., R.d.C., D.K.I. and G.S.R. designed experiments, analysed and discussed data. J.A.M., R.d.C. and D.K.I. wrote the paper. T.M.B. and D.B.A. conducted statistical analyses and consultation. E.M.T., A.M.H. and J.E.Y. provided many years of technical support, data collection and supervision. R.L.H. provided veterinary support. D.L.L. assisted with data interpretation, discussion and paper edits. M.B. performed pathology assessments. D.B. assisted with initial diet formulation and all diet analyses and comparisons. W.F.W. and W.Q. designed and performed the isoprostane assays.

Corresponding authors

Correspondence to Julie A. Mattison, Donald K. Ingram or Rafael de Cabo.

Ethics declarations

Competing interests

D.B.A. has received grants, honoraria, donations and consulting fees from non-profit and for-profit organizations with interest in obesity, including the Frontiers Foundation; Vivus, Inc.; Merck; Eli Lilly & Company; Jason Pharmaceuticals; Kraft Foods; University of Wisconsin; University of Arizona; Paul, Weiss, Wharton & Garrison LLP and Sage Publications.

Supplementary information

Supplementary Information

This file contains Supplementary Tables 1-2, Supplementary Figure 1, Supplementary Text for the figures in the main paper, and a Supplementary Summary. (PDF 220 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mattison, J., Roth, G., Beasley, T. et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321 (2012). https://doi.org/10.1038/nature11432

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature11432

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing