Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta)

Caloric restriction (CR) is the most successful method of extending both me dian and maximal lifespans in rodents and other short-lived species. It is not yet clear whether this method of life extension will be successful in l onger-lived species, possibly including humans; however, trials in rhesus m onkeys are underway. We have examined the cellular proliferative potential of cells from CR and AL (ad libitum fed) monkey skin cells using two differ ent bioassays: colony size analysis (CSA) of dermal fibroblasts isolated an d cloned directly from the skin and betagalactosidase staining at PH 6.0 (B G-6.0) of epidermal cells in frozen sections of skin. Decreases in both pro liferative markers occurred with ape, but no differences were observed betw een CR and AL animals. Skin biopsies were obtained from AL and CR rhesus mo nkeys from two different aging colonies, one at the National Institute on A ging (NIA) and one at the University of Maryland-Baltimore (UMB). These bio psies were used as a source of tissue sections and cells for two biomarkers of aging assays. The CR monkeys had been maintained for 9-12 years on appr oximately 70% of the caloric intake of control AL animals. In the CSA studi es, the fraction of small clones increased significantly and the fraction o f large clones decreased significantly with increasing age in AL monkeys. T he frequency of epidermal BG-6.0 staining cells increased with age in older (>22 years) AL monkeys, but most predominately in those of the UMB colony, which were somewhat heavier than the NIH AL controls. Old monkeys on CR te nded to have fewer BG-6.0-positive cells relative to old AL-derived epiderm is, but this effect was not significant. These results indicate that cellul ar proliferative potential declined with age in Macaca mulatta, but was not significantly altered by CR under these conditions. Although these experim ents are consistent with an absence of effect of CR on monkey skin cell pro liferative potential, we have found in previous experiments with mice that a longer duration of CR (as a fraction of total lifespan) was needed to dem onstrate CR-related improvement in clone size in mice. Further studies on t he now mid-aged monkeys will be needed as their age exceeds 20 years to con clusively rule out an effect of CR on proliferative potential of skin cells from these primates. (C) 1999 Wiley-Liss, Inc.