Common marmosets provide an alternative to macaques as nonhuman primate models of aging
D.H. Abbott, R.J. Colman, W. Saltzman, N.J. Schultz-Darken, J.W. Kemnitz, A. Usborne, A. Trainor, I. Bolton, N.V. Dhurandhar, R.L. Atkinson, N. Binkley
Wisconsin Regional Primate Research Center and Department of Ob/Gyn, University of Wisconsin, Madison, WI 53715
Common marmosets (Callithrix jacchus) are increasingly used as biomedical models of human physiology and pathology, yet little is known about their potential as models of aging. Marmosets are small-bodied (~400g), arboreal, New World anthropoid primates. Their physiological and behavioral adaptations to gum feeding and cooperative breeding, however, are associated with different life challenges and patterns of aging than found in nonhuman primates more typically used in aging research, such as rhesus macaques. Each year, adult females give birth to approximately two sets of dizygotic twins, but there is no clear breeding season and usually only a single, dominant female breeds in each group. In captivity, marmosets are highly tractable and fecund. Maximal lifespan is approximately 12-14 years. The marmoset colony at the Wisconsin Primate Center has been maintained indoors under artificial lighting for 10 years. Most are kept either as male-female pairs and their offspring or as mixed-sex groups of unrelated adults. Approximately 50% of our 300 marmosets are immatures and sub-adults (<1.5 years old), 43% are prime-aged adults (1.5-8 years old) and 7% are over 8 years. The oldest animals reach 14 years. There is a relatively constant (10%) loss of adults for each 2 years of incremental age. Between 70 and 80% of all adults that die or are euthanized because of illness exhibit either lymphosarcoma and/or lymphocytic enteritis (possibly variations of the same disease process), and the former may be linked to marmoset gammaherpesvirus. As females age they continue to give birth at intervals of 150-300 days, but females over 8 years of age produce progressively fewer surviving offspring. Social status within marmoset groups has pronounced consequences for female physiology. In either type of social grouping, about half the subordinate females experience months to years of hypoestrogenism due to hypogonadotropic anovulation. Since estrogen-depletion and age-related bone loss are universal among human populations, and have been shown to occur in Old World monkeys, decreased bone mineral density might be expected in subordinate and older marmosets. Surprisingly, we found no difference between young (2-5 years) and old (8-13 years) males, and old females had higher bone mineral density than young females. In addition, adult female marmosets followed for six months after ovariectomy exhibited no change in spine bone mineral density. Marmosets may have adapted to hypoestrogenism because their breeding system causes individuals to undergo extended periods of low circulating estrogen levels. Furthermore, low social rank is not a stressful existence for female marmosets and is not accompanied by heightened adrenal activity. Adrenocortical function instead becomes less responsive to pituitary adrenocorticotropin, possibly indicative of additional physiological adaptation to hypoestrogenism that may prove beneficial in old animals. Finally, male marmosets inoculated with human adenovirus-36 exhibit increased adiposity with cholesterol lowering and provide the first causal evidence in a primate for this associative finding in humans. The overall potential of the common marmoset suggests it will provide new insights into mechanisms of aging in a primate species. [Supported, in part, by NIH grants RR00167, AG15621, MH60728]
Key words:
marmoset, bone density, adiposity, longevity, hypoestrogenism
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