Contributions of Nonhuman Primates to Research on Aging

Abstract

Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans.

The Exceptional Vulnerability of Humans to Alzheimer’s Disease

“…In their later years, nonhuman primates display typical signs of advanced age, such as immune, cardiovascular, musculoskeletal and reproductive senescence, as well as changes in social engagement [31]. …”

“…However, nonhuman primates age biologically more rapidly than do humans; in addition to manifesting many of the common systemic characteristics of human aging [6, 31], they develop Aβ lesions in the brain at chronological ages that are approximately proportional to their lifespan [30]. Nearly one-third of humans aged 85 or older in the United States manifest AD [58]; based on their known maximum lifespan (above), roughly comparable biological ages in rhesus monkeys would be 28 years, and in squirrel monkeys, 21 years.…”

Glial cell morphological and density changes through the lifespan of rhesus macaques

“…Aging is a normal biological process with changes to numerous physiological functions (see recent review by (Didier et al, 2016) for similarities between primates and humans). Improvements in public health, social services, and healthcare systems worldwide are producing an older human population.…”

On the Social Life and Motivational Changes of Aging Monkeys

“…A recent comprehensive study of motivational changes in a large age-heterogeneous population of Barbary macaques ( Macaca sylvanus ) living at "La Forêt des Singes" in Rocamadour explicitly tested predictions from social selectivity theory, which posits that in light of a shrinking future time perspective, humans become increasingly selective in terms of their social interactions. Given that nonhuman primates most likely have no conception of their limited lifetime, this allowed disentangling the effects of cognitive insights and basal physiological processes that contribute to played an important role in research of physiological aging processes, as they reveal age-related changes similar to those of humans [2][3][4] . Yet, studies on nonhuman primates may also help to develop a better understanding of the determinants of "successful" aging, i.e., how individuals cope with age-related shifts in the availability of resources [5,6] .…”

“…Different psychological theories have attempted to explain the diminishing sociality occurring in old age: according to the "disengagement theory," voluntary withdrawal from society is a biologically determined and inevitable process reflecting waning physical strength, ultimately culminating in death [22] ; the "activity theory," in contrast, presumes that older humans shift their previously pursued social activities to other behaviors that are less physically engaging but still socially satisfying [23] . Although the disengagement theory is no longer very influential in psychology [4] , it still received attention in studies of nonhuman primate behavior [ 18 ; but see 24 ].One of the theories opposing the disengagement theory in human aging research is the "socioemotional selectivity theory" (SST). According to the SST, goals shift across the life span in relation to the perceived future time perspective [25,26] .…”