Nutrition, metabolism, and targeting aging in nonhuman primates

Abstract

Summary This short review focuses on the importance of nonhuman primate nutrition and aging studies and makes the case that a targeted expansion of the use of this highly translatable model would be advantageous to the biology of aging field. First, we describe the high degree of similarity of the model in terms of aging phenotypes including incidence and prevalence of common human age-related diseases. Second, we discuss the importance of the nonhuman primate nutrition and aging studies and the extent to which the outcomes of two ongoing long-term studies of caloric restriction are congruent with short-term equivalent studies in humans. Third, we showcase a number of pharmacological agents previously employed in nonhuman primate studies that display some potential as caloric restriction mimetics. Finally, we present nonhuman primates as an important model for translation of mechanisms of delayed aging identified in studies of shorter-lived animals. Proof of efficacy and safety of candidate longevity agents in nonhuman primates would be a cost-effective means to bring these exciting new avenues a step closer to clinical application.

Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys

“…More recently it has become clear that the benefits of CR in lowering morbidity and mortality are translatable to primates (Mattison et al, 2017), with important implications for human aging biology (Balasubramanian et al, 2017a). The human and nonhuman primate (NHP) response to CR is highly congruent, with similar beneficial effects on bodyweight, body composition, glucoregulatory function, and serum indicators of cardiovascular disease risk noted in both species (Balasubramanian et al, 2017b). Rhesus monkeys share substantial genomic identity with humans (93%) (Zimin et al, 2014), along with many physiological and behavioral features (Colman and Anderson, 2011), and an increase in incidence of conditions such as cancer, diabetes, sarcopenia, and bone loss as a function of age.…”

Ayurveda and the science of aging

“…Deciphering these factors that are also responsible for age-associated diseases will be helpful in drug discovery efforts to decelerate aging [4] , [9] . Among these factors, one that has inspired a lot of excitement is metabolism, and researchers have been trying to understand why caloric restriction extends the life span in mice and other animals [17] , [18] , [19] , [20] , [21] . Metabolizing fewer calories could result in reduced oxidative damage or alternatively, absence of nutrients may trigger certain defense mechanisms that protect the body from decaying.…”

“…Researchers have managed to identify several molecular pathways that govern metabolism. Modification of these pathways or their specific products through proper drug-based interventions, could one day mimic the life expanding effects of caloric restriction in humans without compromising on the food intake [16] , [19] , [20] , [21] , [22] , [23] .…”

“…CR also retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism through which this occurs is unclear [17] , [18] , [19] , [20] , [21] . Therapeutic cloning, body part replacement and stem cell research could one day provide a way to generate cells, body parts, or even entire bodies that do not decay [52] , [53] , [54] .…”

“…CR also retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism through which this occurs is unclear [17] , [18] , [19] , [20] , [21] .…”