Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

Abstract

Although less dramatic than in females, male mammals experience decreasing reproductive function during aging. In primates, multiple facets of the hypothalamic-pituitary-gonadal axis show evidence of gradual age-related decline, including behavioral, neuroendocrine and endocrine alterations such as decreased testosterone levels, reduced circulating dehydroepiandrosterone sulfate (DHEAS) levels, increased numbers of sperm abnormalities, and a general decline in physiological responses. In this review we consider a range of age-related changes in males. These measures, including more subtle aging characteristics, are interesting additional indices for detecting the timing of age-related changes in behavioral, neuroendocrine, and endocrine responses. Evidence of potential effects of calorie restriction as an intervention in reproductive aging is also discussed. A discernable decline occurs in both metabolic and reproductive endocrine processes during male aging. This cascade of events includes neuroendocrine and behavioral changes; biomarkers such as circulating DHEAS also show clear age-related decline. The varied changes that occur during male aging are considered in the context of primate aging in general.

Impact of Moderate Calorie Restriction on the Reproductive Neuroendocrine Axis of Male Rhesus Macaques~!2009-07-12~!2009-11-05~!2010-01-02~!

“…A growing body of evidence from rhesus macaque studies suggests that moderate CR may delay the onset of age-related pathologies even in long-lived species [12, 19, 22]. On the other hand, the mechanisms underlying CR’s health-promoting properties are poorly understood.…”

“…Overall, the data suggest that moderate CR has no obvious lasting negative impact on the reproductive neuroendocrine axis and has only a modest influence on pituitary and testicular gene expression. Previously-reported advantageous health benefits of CR [12, 19, 21] and eventual mimetic exploitation may then be achievable without causing significant long-term impairment of the HPG axis. It remains to be elucidated how the observed changes in pituitary TSHR and CGA expression levels are manifested physiologically under a 30%CR nutritional paradigm, but most likely they are related to altered metabolic function rather than any type of reproductive neuroendocrine function.…”

“…A few examples of age-related homeostatic imbalance include decreased stress responses, increased pathology, decline in memory function, and documented alterations in circadian organization, such as changes in hormonal rhythms, core body temperature and sleep/wake cycles [13–15]. In males, the age-related reproductive demise occurs with functional deterioration at several sites along the hypothalamic-pituitary-gonadal (HPG) axis, including reduced testosterone (T) production, decreased hypothalamic gonadotropin-releasing hormone (GnRH), and altered pituitary gland release of gonadotropins [16–19]. …”

Aging‐related reproductive decline in the male spider monkey (Ateles geoffroyi)

“…Our study shows that there is an age‐related reproductive decline in black‐handed male spider monkeys, although aging might be one among other factors accounting for variations in sperm numbers and hormonal levels [9, 13, 14], as the between‐subject variability suggests. Changes described here agree with other studies carried out in non‐human and human primates.…”

Mechanisms of reproductive aging: conserved mechanisms and environmental factors

“…Males also exhibit age‐related reproductive decline albeit more gradual than in females 19 . Moreover, there is evidence for benefits of dietary interventions including caloric restriction 12,20,21 . A key element in the aging process is increasing disruption in biological rhythms; in the case of reproductive endocrine function there are altered circadian rhythms that occur even at the level of the pituitary gland 22 .…”