Dysregulated homeostatic pathways in sarcopenia among frail older adults

​Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical netowrk of relationships among different dysregulated pathways involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging to community-dwelling prefrail and frail older persons to derive measures of multiple physiological pathways, and structural equation modeling to generate path network modeals of the multisystem physiological dysregulations associated with muscle mass and function (MMF). Insulin-leptin signaling and energy regulation, anabolic sex steroid regulation (testosterone, leptin), and tissue oxygenation (hemoglobin, red cell count) appear to be primary mediating factors exerting direct influences on MMF. There was additionally secondary mediatory involvement of myocyte- and adipocyte-derived cytokines, hypothalamic pituitary adrenal (HPA) stress hormones (cortisol, DHEAS), glomerular function, and immune cell regulatory and inglammatory cytokines and glycoproteins. We conclude that within a hierarchical network of multisystem physiological dysregulations in sarcopenia, dysregulated anabolic and catabolic pathways via sex steroids and insulin-leptin dual signaling and tissue hypoxemia are primary physiological dysregulations responsible for sarcopenia and frailty.

SOURCE:
Aging Cell

DOI:
https://doi.org/10.1111/acel.12842

AUTHOR(S):
Ng Tze Pin, Lu Yan Xia, Robin Choo, Crystal Tan Tze Ying, Ma Shwe Zin Nyunt, Gao Qi, Esther Mok Wing Hei, Anis Larbi