A Review of the Use of Primates in Aging Research
This review paper makes a good companion piece to another review on primates in aging research published last year. Perhaps the most well known primate studies of aging are the still ongoing and decades-long studies of calorie restriction in rhesus macaques, unlikely to be repeated given the cost and the debate over the quality of the resulting data and the underlying design of the studies. There are many other studies involving the use of various non-human primate species to study aging and age-related disease, however, some of which are just as interesting.
The choices made in the use of animals in aging research are a matter of economics: longer life spans and species closer to ours lead to studies that are slower and more costly, but the data is more likely to be useful and relevant. In practice the costs are too high, and thus most exploratory research into the biochemistry of aging starts out in very short-lived and evolutionarily distant species such as worms and flies. There is a high rate of failure for the results to translate into mammals, but even then the cost of progress is much lower that would be the case if carrying out that initial exploration in mice or other longer-lived mammals. All research involving primate studies has already passed through stages of exploration and validation in worms, flies, mice, and frequently other mammals as well; only the more established lines of research can justify the time and funding needed for further studies in primates.
Nonhuman primates share similar physiology and a close phylogenetic relationship to humans. The use of nonhuman primates in comparative experimental studies thus contributes to our knowledge about aging processes and translation of applications for improving health span in humans and other animals. With the growing development of antiaging strategies, it is expected that nonhuman primates will additionally be highly relevant for preclinical studies testing antiaging strategies. Correlates of average natural life span of an organism are highly complex, but body size in conjunction with metabolism, reproduction, immunity, and environmental stress, among other factors, is associated with average longevity such that larger animal species tend to live longer. Interestingly, human and nonhuman primates exhibit unusually longer average life spans that are nearly 4-fold higher than those of most other mammals relative to their body sizes. In addition, nonhuman primates exhibit similar key life span metrics as humans, such as higher infant mortality rate, followed by lower mortality during the juvenile stage and then an extended period of increasing age-related morbidity and mortality.
By far, the predominant nonhuman primate species utilized in biomedical research facilities as well as for studies on aging are rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fasicularis). Specifically, among the facilities with nonhuman primates in North America that were recently surveyed, 80% housed rhesus macaques of Indian or Chinese origin, followed closely by cynomolgus macaques housed in 73% of the facilities. Aspects of aging research studies that utilize macaques include neurobiology, anatomy, physiology, cognition, and behavior, as well as reproductive senescence, caloric restriction (CR), and immune senescence. The use of macaques in research appears to represent the best compromise between phylogenetic and physiologic relatedness to humans, cost efficiency, life span, resources, expertise in animal husbandry practices, and adaptability for translation of results to humans. To improve efficiency, accessibility, and applicability, however, increasing emphasis is being placed on purpose-bred animals and further advancing animal husbandry practices so that lower primates also may be included for relevant model development of research on aging.
Prosimians, or "premonkeys," are the most phylogenetically distant nonhuman primates from humans. Among the prosimians, grey mouse lemurs (Microcebus murinus) have been the most extensively studied for relating processes of aging in relation to humans. For example, the mouse lemur was the first nonhuman primate species to demonstrate a relationship between cerebral atrophy and cognitive decline with aging that simulated what was seen in aging humans. Neuroscience studies about memory, behavior, and psychomotor function have utilized both captive and wild mouse lemurs. The use of prosimians in research is more cost-efficient, but limitations include their smaller size that restricts specimen sampling; differences in metabolic, biochemical, and endocrine responses compared with humans; and a need for continued development in animal husbandry techniques to reduce stress-related behaviors of captive prosimians.