Aging research using the common marmoset: Focus on aging interventions

Abstract

Traditional animal models have been used to make seminal discoveries in biomedical research including a better understanding of the biology of the aging process. However, translation of these findings from laboratory to clinical populations has likely been hindered due to fundamental biological and physiological differences between common laboratory animals and humans. Non-human primates (NHP) may serve as an effective bridge towards translation, and short-lived NHP like the common marmoset offer many advantages as models for aging research. Here, we address these advantages and discuss what is currently understood about the changes in physiology and pathology that occur with age in the marmoset. In addition, we discuss how aging research might best utilize this model resource, and outline an ongoing study to address whether pharmaceutical intervention can slow aging in the marmoset. With this manuscript, we clarify how common marmosets might assist researchers in geroscience as a potential model for pre-clinical translation.

Rapamycin/metformin co‐treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice

“…Multiple preclinical studies indicate that rapamycin, and its analogues, have positive effects on various chronic age‐related impairments, including cardiomyopathy (Das et al, 2014 ; Reifsnyder et al, 2018 ); nephropathy (Reifsnyder et al, 2014 ; Yang et al, 2007 ); neurodegeneration, including Alzheimer's disease (Van Skike et al, 2021 ); and osteoporosis (Kneissel et al, 2004 ). Positive results for such widespread application have encouraged feasibility studies for larger mammals: dogs (Urfer et al, 2017 ), nonhuman primates (Ross et al, 2015 ; Ross & Salmon, 2019 ; Sills et al, 2019 ), and humans (Kraig et al, 2018 ). Although broad use of rapamycin as a generalized antiaging treatment has been contraindicated by its immunosuppressive and hyperglycemic effects, recent research indicates that immunosuppressive effects can be attenuated, and potentially reversed, by alternate treatment schedules and lower doses than used for organ transplantation, and by use of various rapalogues (Arriola Apelo et al, 2016 ; Chen et al, 2009 ; Mannick et al, 2018 ; Walters & Cox, 2018 ).…”

Age-Related Alterations in Brain Perfusion, Venous Oxygenation, and Oxygen Metabolic Rate of Mice: A 17-Month Longitudinal MRI Study

“…In addition, there are limitations of using animal models to study human conditions. In this case, the aging process in humans is expected to be different from that in mice in many aspects (79)(80)(81). Aged mice often do not develop neurodegeneration and have low prevalence of cardiovascular disease, possibly due to species differences in physiology, disparity in maximal lifespan, diet, and environmental factors.…”

Hallmarks of Testicular Aging: The Challenge of Anti-Inflammatory and Antioxidant Therapies Using Natural and/or Pharmacological Compounds to Improve the Physiopathological Status of the Aged Male Gonad

“…In fact, in vivo studies performed in rats and mice showed that rapamycin increased testicular degeneration following an orderly loss of all stages of spermatogenesis from the most mature to least differentiated cells (i.e., spermatids, spermatocytes, differentiating spermatogonia, and primary spermatogonia) [188] due to inhibition of proliferation [191] and differentiation [192] of spermatogonia. There is an ongoing long-term study to test the effect of a daily dose of rapamycin on longevity and healthy aging in a cohort of middle-aged marmosets (mixed sexes) [193]. The results of this work should indicate whether rapamycin will affect the testes of this non-human primate species similarly to its effects in laboratory rodents.…”