Letter | Published:

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

Nature volume 489, pages 318321 (13 September 2012) | Download Citation

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.

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References

  1. 1.

    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)

  2. 2.

    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)

  3. 3.

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

  4. 4.

    , , & Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J. Gerontol. A 63, 556–559 (2008)

  5. 5.

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

  6. 6.

    , , , & Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. J. Gerontol. A 58, B212–B219 (2003)

  7. 7.

    , & Genotype and age influence the effect of caloric intake on mortality in mice. FASEB J. 17, 690–692 (2003)

  8. 8.

    , , & Source of dietary carbohydrate affects life span of Fischer 344 rats independent of caloric restriction. J. Gerontol. A 50A, B148–B154 (1995)

  9. 9.

    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)

  10. 10.

    et al. in Calorie Restriction, Aging, and Longevity (eds , , & ) 55–78 (Springer, 2010)

  11. 11.

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

  12. 12.

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

  13. 13.

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

  14. 14.

    & in Methods in Aging Research (ed. ) 249–267 (CRC, 1998)

  15. 15.

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

  16. 16.

    Survival Analysis Using SAS: A Practical Guide (SAS Institute, 1995)

  17. 17.

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

  18. 18.

    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)

  19. 19.

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

  20. 20.

    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)

  21. 21.

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

  22. 22.

    , , , & Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell 9, 92–95 (2010)

  23. 23.

    , & Does caloric restriction extend life in wild mice? Aging Cell 5, 441–449 (2006)

  24. 24.

    & 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)

  25. 25.

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

  26. 26.

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

  27. 27.

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

  28. 28.

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

  29. 29.

    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)

  30. 30.

    , , , & SAS for Mixed Models (SAS Institute Inc., 2006)

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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

Affiliations

  1. Laboratory of Experimental Gerontology, National Institute on Aging, NIH Animal Center, 16701 Elmer School Road Building 103, Dickerson, Maryland 20842, USA

    • Julie A. Mattison
    • , Edward M. Tilmont
    • , April M. Handy
    •  & Jennifer E. Young
  2. GeroScience, 1124 Ridge Road Pylesville, Maryland 21132, USA

    • George S. Roth
  3. Department of Biostatistics, Ryals Public Health Bldg 343C University of Alabama at Birmingham, 1530 3rd Avenue S, Birmingham, Alabama 35294, USA

    • T. Mark Beasley
  4. SoBran, Inc., 4000 Blackburn Lane, Suite 100, Burtonsville, Maryland 20866, USA

    • April M. Handy
  5. National Institute of Allergy and Infectious Disease, NIH Animal Center, 16701 Elmer School Road, Building 102, Dickerson, Maryland 20842, USA

    • Richard L. Herbert
  6. Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, 251 Bayview Boulevard Room 08C228, Baltimore, Maryland 21224, USA

    • Dan L. Longo
  7. Office of Energetics, University of Alabama at Birmingham, 1665 University Boulevard, RPH 140J Birmingham, Alabama 35294, USA

    • David B. Allison
  8. Office of the Director, Diagnostic and Research Services Branch, NIH, Bldg 28A, Room 114, 28 Service Road West, Bethesda, Maryland 20814, USA

    • Mark Bryant
  9. Office of the Director, Diagnostic and Research Services Branch, NIH, Building 14A, Room 119A, 14 Service Road West, Bethesda, Maryland 20814, USA

    • Dennis Barnard
  10. Department of Physiology/Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA

    • Walter F. Ward
  11. Department of Cellular and Structural Biology/ Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA

    • Wenbo Qi
  12. Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA

    • Donald K. Ingram
  13. Laboratory of Experimental Gerontology, National Institute on Aging, NIH, 251 Bayview Boulevard Suite 100, Baltimore, Maryland 21224, USA

    • Rafael de Cabo

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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.

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.

Corresponding authors

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

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    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.

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DOI

https://doi.org/10.1038/nature11432

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