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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.

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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.

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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.

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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.

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

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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.

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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)

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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

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