Authors
Pendergrass WR. Lane MA. Bodkin NL. Hansen BC. Ingram DK. Roth GS. Yi
L. Bin H. Wolf NS.
Institution
Department of Pathology, University of Washington, Seattle 98195, USA.
Title
Cellular proliferation
potential during aging and caloric restriction in rhesus
monkeys (Macaca mulatta).
Source
Journal of Cellular Physiology. 180(1):123-30, 1999 Jul.
Abstract
Caloric restriction (CR) is the most successful method of extending both
median 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
longer-lived species, possibly including humans; however, trials in rhesus
monkeys are underway. We have examined the cellular
proliferative potential of cells from CR and AL (ad libitum
fed) monkey skin cells using two different bioassays: colony size analysis
(CSA) of dermal fibroblasts isolated and cloned directly from the skin and
beta-galactosidase staining at pH 6.0 (BG-6.0) of epidermal cells in frozen
sections of skin. Decreases in both proliferative markers occurred with age,
but no differences were observed between CR and AL animals. Skin biopsies
were obtained from AL and CR rhesus monkeys from two different aging
colonies, one at the National Institute on Aging (NIA) and one at the
University of Maryland-Baltimore (UMB). These biopsies 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 approximately 70% of the
caloric intake of control AL animals. In the CSA studies, the fraction of
small clones increased significantly and the fraction of large clones
decreased significantly with increasing age in AL monkeys. The 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 tended to have
fewer BG-6.0-positive cells relative to old AL-derived epidermis, but this
effect was not significant. These results indicate that
cellular proliferative potential declined
with age in Macaca mulatta, but was not significantly altered by CR under
these conditions. Although these experiments are consistent with an absence
of effect of CR on monkey skin cell proliferative potential,
we have found in previous experiments with mice that a longer duration of CR
(as a fraction of total lifespan) was needed to demonstrate CR-related
improvement in clone size in mice. Further studies on the now mid-aged
monkeys will be needed as their age exceeds 20 years to conclusively rule out
an effect of CR on proliferative potential of skin cells
from these primates.