Life extension by calorie restriction (CR) has been widely reported in a variety of species and remains on the forefront of anti-aging intervention studies. We report healthspan and survival effects of CR from a 23-year study in rhesus macaques conducted at the National Institute on Aging (NIA). CR initiated at older ages did not increase survival relative to Controls; however, CR monkeys demonstrated an improved metabolic profile and may have less oxidative stress as indicated by plasma isoprostane levels. When initiated in young monkeys, there was a trend (p=0.06) for a delay in age-associated disease onset in CR monkeys; but again, survival curves were not improved, in contrast to another study reported in the literature. This suggests that the effects of CR in a long-lived animal are complex and likely dependent on a variety of environmental, nutritional, and genetic factors.

SUMMARY Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/− resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys.

SUMMARY Central arterial wall stiffening driven by a chronic inflammatory milieu accompanies arterial diseases, the leading cause of cardiovascular (CV) morbidity and mortality in Western society. Increase in central arterial wall stiffening, measured as an increase in aortic pulse wave velocity (PWV), is a major risk factor for clinical CV disease events. However, no specific therapies to reduce PWV are presently available. In rhesus monkeys, a two-year diet high in fat and sucrose (HFS) increases not only body weight and cholesterol, but also induces prominent central arterial wall stiffening and increases PWV and inflammation. The observed loss of endothelial cell integrity, lipid and macrophage infiltration, and calcification of the arterial wall were driven by genomic and proteomic signatures of oxidative stress and inflammation. Resveratrol prevented the HFS-induced arterial wall inflammation and the accompanying increase in PWV. Dietary resveratrol may hold promise as a novel therapy to ameliorate increases in PWV.

Many species of African nonhuman primates are natural hosts for individual strains of simian immunodeficiency virus (SIV). These infected animals do not, however, develop AIDS. Here we show that multiple species of African nonhuman primate species characteristically have low frequencies of CD4 ؉ T cells and high frequencies of both T cells that express only the alpha-chain of CD8 and double-negative T cells. These subsets of T cells are capable of eliciting functions generally associated with CD4 ؉ T cells, yet these cells lack surface expression of the CD4 protein and are, therefore, poor targets for SIV in vivo. These data demonstrate that coevolution with SIV has, in several cases, involved downregulation of receptors for the virus by otherwisesusceptible host target cells. Understanding the genetic factors that lead to downregulation of these receptors may lead to therapeutic interventions that mimic this modulation in progressive infections.