Dietary restriction (DR) consistently slows the rate of aging, while reducing the incidence and delaying the onset of age-related disease in nonprimate species. The goal of this program is to determine the effects of DR on aging and disease in rhesus monkeys. This component research project is designed to evaluate the impact on DR on the regulation of metabolism during aging from an integrative, physiologic standpoint. Body composition and distribution of body fat will be measured and related to insulin sensitivity and to insulin and glucose levels. The relationship on insulin levels to metabolic rate will be assessed. The following hypotheses will be tested: 1) DR will result in reductions in body weight, body fat and lean body mass, followed by stabilization at lower levels. These changes will be accompanied by sustained alternations in both the level and efficiency of energy utilization. 2) DR-association changes in glucoregulation and metabolic rate represent fundamental aging processes that are at least partially independent of changes in body composition, and consequently will be associated with other measures of biologic aging. In this context, elucidating the effects of aging and DR on glucose, via nonenzymatic glycosylation of proteins and DNA, is a general mediator of age-related change. This project will also probe the cellular mechanisms of increased insulin sensitivity with DR using studies of the GLUT-4 glucose transporter levels in skeletal muscle. Improved understanding of the hyperinsulinemia and elevated glucose levels characteristic of middle age is important, because these conditions are associated with a greater risk for many age-related diseases, including hypertension, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, glaucoma, cataract, and nephropathy.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
United States
Zip Code
Maegawa, Shinji; Lu, Yue; Tahara, Tomomitsu et al. (2017) Caloric restriction delays age-related methylation drift. Nat Commun 8:539
Mattison, Julie A; Colman, Ricki J; Beasley, T Mark et al. (2017) Caloric restriction improves health and survival of rhesus monkeys. Nat Commun 8:14063
Polewski, Michael A; Burhans, Maggie S; Zhao, Minghui et al. (2015) Plasma diacylglycerol composition is a biomarker of metabolic syndrome onset in rhesus monkeys. J Lipid Res 56:1461-70
Fowler, Cynthia G; Chiasson, Kirstin Beach; Colman, Ricki J et al. (2015) Hyperinsulinemia/diabetes, hearing, and aging in the University of Wisconsin calorie restriction monkeys. Hear Res 328:78-86
Barger, Jamie L; Anderson, Rozalyn M; Newton, Michael A et al. (2015) A conserved transcriptional signature of delayed aging and reduced disease vulnerability is partially mediated by SIRT3. PLoS One 10:e0120738
Colman, Ricki J; Beasley, T Mark; Kemnitz, Joseph W et al. (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5:3557
Sridharan, Aadhavi; Bendlin, Barbara B; Gallagher, Catherine L et al. (2014) Effect of age and calorie restriction on corpus callosal integrity in rhesus macaques: a fiber tractography study. Neurosci Lett 569:38-42
Pugh, Thomas D; Conklin, Matthew W; Evans, Trent D et al. (2013) A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys. Aging Cell 12:672-81
Willette, A A; Coe, C L; Birdsill, A C et al. (2013) Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques. Age (Dordr) 35:2215-27
Csiszar, Anna; Sosnowska, Danuta; Tucsek, Zsuzsanna et al. (2013) Circulating factors induced by caloric restriction in the nonhuman primate Macaca mulatta activate angiogenic processes in endothelial cells. J Gerontol A Biol Sci Med Sci 68:235-49

Showing the most recent 10 out of 120 publications