Comparative lifespan and healthspan of nonhuman primate species common to biomedical research.

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Accurate measures of chronological aging are essential for inferences into genetic, demographic, and physiological variables driving differences in NHP lifespan within and between species. Understanding NHP lifespans is relevant to public health because unraveling the demographic, molecular, and clinical bases of health across the life course in translationally relevant NHP species is fundamentally important to the study of human aging. Data from more than 110,000 captive individual NHP were contributed by 15 major research institutions to generate sex-specific Kaplan-Meier survival curves using uniform methods in 12 translational aging models: Callithrix jacchus (common marmoset), Chlorocebus aethiops sabaeus (vervet/African green), Macaca fascicularis (cynomolgus macaque), M. fuscata (Japanese macaque), M. mulatta (rhesus macaque), M. nemestrina (pigtail macaque), M. radiata (bonnet macaque), Pan troglodytes spp. (chimpanzee), Papio hamadryas spp. (baboon), Plecturocebus cupreus (coppery titi monkey), Saguinus oedipus (cotton-top tamarin), and Saimiri spp. (squirrel monkey). After employing strict inclusion criteria, primary analysis results are based on 12,269 NHP that survived to adulthood and died of natural/health-related causes. A secondary analysis was completed for 32,616 NHP that died of any cause. For the primary analyses, we report ages of 25th, 50th, 75th, and 85th percentiles of survival, maximum observed ages, rates of survivorship, and sex-based differences captured by quantile regression models and Kolmogorov-Smirnov tests. Our findings show a pattern of reduced male survival among catarrhines (African and Asian primates), especially macaques, but not platyrrhines (Central and South American primates). For many species, median lifespans were lower than previously reported. An important consideration is that these analyses may offer a better reflection of healthspan than lifespan. Captive NHP used in research are typically euthanized for humane welfare reasons before their natural end of life, often after diagnosis of their first major disease requiring long-term treatment with reduced quality of life (e.g., endometriosis, cancer, osteoarthritis). Supporting the idea that these data are capturing healthspan, for several species typical age at onset of chronic disease is similar to the median lifespan estimates. This data resource represents the most comprehensive characterization of sex-specific lifespan and age-at-death distributions for 12 biomedically relevant species, to date. The results clarify the relationships among NHP ages and will provide a valuable resource for the aging research community, improving human-NHP age equivalencies, informing investigators of the expected survival rates of NHP assigned to studies, providing a metric for comparisons in future studies, and contributing to our understanding of the factors that drive lifespan differences within and among species.

Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta).

Hair loss is common in macaque colonies. Very little is known about the relationship between psychological stress and hair loss. We initially examined alopecia and hair cortisol concentrations in 198 (89 male) rhesus macaques from three primate centers and demonstrated replicability of our previous finding that extensive alopecia (>30% hair loss) is associated with increased chronic cortisol concentrations and significantly affected by facility. A subset of these monkeys (142 of which 67 were males) were sampled twice approximately 8 months apart allowing us to examine the hypotheses that gaining hair should be associated with decreases in cortisol concentrations and vice versa. Hair loss was digitally scored using ImageJ software for the first sample. Then visual assessment was used to examine the second sample, resulting in three categories of coat condition: (i) monkeys that remained fully haired; (ii) monkeys that remained alopecic (with more than 30% hair loss); or (iii) monkeys that showed more than a 15% increase in hair. The sample size for the group that lost hair was too small to be analyzed. Consistent with our hypothesis, monkeys that gained hair showed a significant reduction in hair cortisol concentrations but this effect only held for females. Coat condition changed little across sampling periods with only 25 (11 male) monkeys showing a greater than 15% gain of hair. Twenty (7 male) monkeys remained alopecic, whereas 97 (49 males) remained fully haired. Hair cortisol was highly correlated across samples for the monkeys that retained their status (remained alopecic or retained their hair). Am. J. Primatol. 79:e22547, 2017. © 2016 Wiley Periodicals, Inc.

Factors influencing alopecia and hair cortisol in rhesus macaques (Macaca mulatta).

BACKGROUND: Alopecia can occur in captive non-human primates, but its etiology is poorly understood. The purpose of this study was to assess alopecia and hair cortisol in rhesus monkeys and to identify the potential risk factors. METHODS: Subjects were 117 rhesus monkeys at two National Primate Research Centers. Photographs and hair samples were obtained during routine physicals. Photographs were analyzed using Image J software to calculate hair loss, and hair samples were assayed for cortisol. RESULTS: Age, days singly housed, and their interactions contributed to the alopecia model for both facilities. Sex and location changes contributed to the hair cortisol model for Facility 1; sedations contributed for Facility 2. Alopecia and hair cortisol were associated at Facility 1. CONCLUSIONS: Captive management practices can affect alopecia and hair cortisol. However, there are facility differences in the relationship between alopecia and hair cortisol and in the effect of intrinsic variables and management procedures.

Hair loss and hypothalamic-pituitary-adrenocortical axis activity in captive rhesus macaques (Macaca mulatta).

Hair loss is a common problem in captive macaque colonies. A potential factor is the possible influence of stressful environments in the development of hair loss. We examined the relationship between hair loss and chronic hypothalamic-pituitary-adrenal (HPA) axis activity by measuring cortisol in hair. Adult male and female rhesus macaques housed at 3 primate facilities in the United States were screened for degree of hair loss and observed for evidence of hair-plucking behavior. Hair samples and photographic data were obtained from 99 subjects, none of which were hair-pluckers. Macaques with greater than 30% hair loss (alopecia group) showed higher concentrations of hair cortisol than did those with less than 5% hair loss (control group), a finding that was unrelated to age, body weight, or the month in which the sample was collected. Hair loss scores were positively correlated with hair cortisol levels across all monkeys and within the alopecic group alone. In addition, the strong relationship between hair cortisol and alopecia was noted in 2 but not the third facility. Friction with cage surfaces appeared to contribute to hair loss in 18 monkeys. These findings suggest that stress may be one of several factors related to hair loss in some captive nonhuman primates, although whether this relationship is causal or merely correlational is unclear. Moreover, the source of the additional cortisol in the hair of alopecic monkeys (that is, from the circulation or from local synthesis in the skin) remains to be determined.

Long-term ovariectomy alters social and anxious behaviors in semi-free ranging Japanese macaques.

Symptoms of anxiety and depression often occur in young women after complete hysterectomy and in older women during menopause. There are many variables that are hard to control in human population studies, but that are absent to a large extent in stable nonhuman primate troops. However, macaques exhibit depressive and anxious behaviors in response to similar situations as humans such as isolation, stress, instability or aggression. Therefore, we hypothesized that examination of behavior in ovariectomized individuals in a stable macaque troop organized along matriarchal lineages and in which individuals have social support from extended family, would reveal effects that were due to the withdrawal of ovarian steroids without many of the confounds of human society. We also tested the hypothesis that ovariectomy would elicit and increase anxious behavior in a stressful situation such as brief exposure to single caging. Japanese macaques (Macaca fuscata) were ovariectomized (Ovx) or tubal-ligated (intact controls) at 3 years of age and allowed to mature for 3 years in a stable troop of approximately 300 individuals. Behaviors were recorded in the outdoor corral in the third year followed by individual temperament tests in single cages. There was no obvious difference in anxiety-related behaviors such as scratching between Ovx and tubal-ligated animals in the corral. Nonetheless, compared to tubal-ligated animals, Ovx animals exhibited a significant decrease in (1) positive social behavior, (2) initiating dominance behavior, (3) time receiving grooming, (4) locomoting, (5) mounting behavior, and in (6) consort behavior. However, Ovx females exhibited a significant increase in (1) consummatory behavior and (2) object play compared to tubal-ligated controls. In the individual temperament tests, Ovx individuals exhibited an increase in anxiety-related behaviors. There was no difference in adrenal weight/body weight suggesting that neither group was under chronic stress. These data indicate that ovarian hormones enable females to successfully navigate their social situation and may reduce anxiety in novel situations.

Heritability of fearful-anxious endophenotypes in infant rhesus macaques: a preliminary report.

BACKGROUND: Research efforts to discover the genetic underpinnings of anxiety and depression is challenging because of the etiologic heterogeneity inherent to these disorders. These efforts might be aided by the study of related behavioral phenotypes in model organisms, such as monkeys. METHODS: Eighty-five rhesus monkeys (Macaca mulatta) from the Oregon National Primate Research Center were drawn from a standard matriarchal colony and tested for behavioral response in four testing paradigms designed to elicit fearful-anxious reactions. Heritabilities were estimated using variance component-based quantitative genetic analyses with much of the genetic information arising from paternal half-sibs. RESULTS: Individual behaviors reflecting increased distress responses (e.g., vocalizations and teeth grinding) and behavioral inhibition (e.g., latency to leave mother, latency to inspect novel fruit) showed significant heritability, even though a small number of monkeys were assessed. Exploratory factor analyses identified seven clusters of behaviors across tests, some of which were found to be heritable. CONCLUSIONS: These results indicate that several specific fearful-anxious behaviors in infant rhesus monkeys are heritable within this colony. Accordingly, these phenotypes, which are believed to represent the genetic liability for anxiety and depression, are good candidates for further genetic investigation in this population.