Age-related pathology and biosenescent markers in captive rhesus macaques

Abstract

During the past 15 years, our aging colony of rhesus monkeys, consisting of animals from 20 to 37 years of age, had an annual average population of 88.2 live monkeys and, of this population, an annual average of 13.9 monkeys died spontaneously or were terminated due to severe illness. From 1980 to 1994, a total of 175 autopsies of rhesus macaques, from 20 to 37 years of age, were performed. By cumulative autopsy data, the incidence of age-related pathology in various organs was surveyed. Major geriatric diseases such as coronary sclerosis, emphysema, degenerative joint disorders, cancer, and cerebral amyloid plaque began to develop in 10 to 40% of macaques after 20 years and the incidence significantly increased after 26 years of age. Approximately 12% of aged macaques from 20 to 30 years of age died annually due to such geriatric diseases with severe complications. The average survival rate indicated that half the population at 20 years of age died by 25 years and 73% died by 30 years of age. Less than 10% of macaques survived over 30 years. Using these aged macaques as well as other juvenile to adult monkeys in our Center, clinical opththalmological and reproductive endocrinological studies, and magnetic resonance imaging (MRI) of the brain were conducted to define bioaging markers of captive rhesus monkeys. Cataracts began to develop in 20% of rhesus monkeys at 20 to 22 years of age and the rate significantly increased after 26 years of age. Menopause occurred at 26 to 27 years of age. Multiple cerebral infarctions and iron deposits in the globus pallidus and substantia nigra were detected by MRI in the aged brains. These geriatric disorders in captive aged macaques appear to be natural aging outcomes, since the simple lifestyle of these captive animals offers minimal exposure to environmental factors. Our data will offer useful paradigms for preventive or experimental studies on age-related diseases.

Assessment of Hormonally Active Agents in the Reproductive Tract of Female Nonhuman Primates

“…A recent longitudinal study of chronic diseases in aged rhesus macaques has shown an incidence of breast cancer that is comparable to that seen in women in the United States (43). We have identi ed 3 endom etrial polyps in tamoxifen-treated animals, but otherwise neoplasms have not been induced in the relatively short treatment periods used in our studies.…”

The Macaque Endometrium, with Special Reference to the Cynomolgus Monkey (Macaca fascicularis)

“…Menopause involves a gradual decrease in the number and regularity of menstrual cycles, ending with the permanent cessation of menses. A sustained high level of serum luteinizing hormone (LH) concomitant with low levels of estradiol is used as a clinical marker of menopause (Uno 1997). In the absence of sufficient estrogenic stimulation, because of the decrease in circulating levels of estradiol as the result of ovarian aging, the endometrium undergoes progressive involution (Figure 39).…”

Dietary Interventions, Cardiovascular Aging, and Disease

“…Moreover, aging Rhesus macaque develops many of the same phenotypes observed in aging humans, including graying and thinning of hair, sarcopenia, and increased incidence of diabetes mellitus, cancer, and other aging-related diseases. 85,86 To date, only 2 major projects have been designed to evaluate the long-term effects of moderate CR on general physiology, health span, and lifespan in nonhuman primates. However, these studies have yielded complex, if not contradictory, results.…”