Conservation of physiological dysregulation signatures of aging across primates

Abstract

Two major goals in the current biology of aging are to identify general mechanisms underlying the aging process and to explain species differences in aging. Recent research in humans suggests that one important driver of aging is dysregulation, the progressive loss of homeostasis in complex biological networks. Yet, there is a lack of comparative data for this hypothesis, and we do not know whether dysregulation is widely associated with aging or how well signals of homeostasis are conserved. To address this knowledge gap, we use unusually detailed longitudinal biomarker data from 10 species of nonhuman primates housed in research centers and data from two human populations to test the hypotheses that (a) greater dysregulation is associated with aging across primates and (b) physiological states characterizing homeostasis are conserved across primates to degrees associated with phylogenetic proximity. To evaluate dysregulation, we employed a multivariate distance measure, calculated from sets of biomarkers, that is associated with aging and mortality in human populations. Dysregulation scores positively correlated with age and risk of mortality in most nonhuman primates studied, and signals of homeostatic state were significantly conserved across species, declining with phylogenetic distance. Our study provides the first broad demonstration of physiological dysregulation associated with aging and mortality risk in multiple nonhuman primates. Our results also imply that emergent signals of homeostasis are evolutionarily conserved, although with notable variation among species, and suggest promising directions for future comparative studies on dysregulation and the aging process.

An Emergent Integrated Aging Process Conserved Across Primates

“…While significant variation exists in the characterization and consequences of integrated albunemia in different species, this process clearly has a broader evolutionary role across primates and is not restricted to humans or closely related species. Our current results complement another recent study using parts of the same primate database to demonstrate conserved patterns of physiological dysregulation across primates, with strong implications for aging and mortality (27). Together, these studies provide evidence for evolutionarily broad patterns of aging and for nonhuman primates as valuable models of emergent processes and aging.…”

“…However, most studies on nonhuman primates are restricted to a few commonly studied species rather than cross-species comparisons, and few tackle ideas involving physiological integration (but see ref. (27)).…”

Robust Physiological Metrics From Sparsely Sampled Networks

“…Third, this signal should not depend strongly on any single biomarker, implying that (a) the choice of biomarkers to include is not crucial, and (b) the signal should increase monotonically (but with diminishing marginal returns) as the number of biomarkers is increased. All of these predictions have now been confirmed by multiple studies ( Cohen et al, 2013 , 2014 , 2015a , 2018c ; Arbeev et al, 2016 ; Dansereau et al, 2019 ; Kraft et al, 2020 ; Liu, 2020 ). The third prediction is particularly important from a complex systems perspective, as it implies that the signal is diffuse or distributed in the physiological networks, and thus robustly estimable from subsamples of biomarkers even without detailed knowledge of network structure.…”

Insights from evolutionarily relevant models for human ageing

“…R. Soc. B 375: 20190605 compatible, information [86,87]. Comparative research can be designed by testing for features of previously identified emergent processes (top-down), or by using variation in the data to organically identify axes of age-related change (bottom-up).…”