Dysregulated homeostatic pathways in sarcopenia among frail older adults

Abstract

Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical network 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 models 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 inflammatory 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.

Inter-correlations Among Clinical, Metabolic, and Biochemical Parameters and Their Predictive Value in Healthy and Overtrained Male Athletes: The EROS-CORRELATIONS Study

“…Also, although oxidative stress leads to muscle hypertrophy, chronic stress mediated by the HPA axis, leads to the opposite direction (82)(83)(84)(85). Indeed, alterationsof the HPA axis disrupt the metabolism of the muscle tissue, toward a negative balance between protein generation and degradation, eventually leading to muscle mass loss (86)(87)(88)(89).…”

“…Indeed, alterationsof the HPA axis disrupt the metabolism of the muscle tissue, toward a negative balance between protein generation and degradation, eventually leading to muscle mass loss (86)(87)(88)(89). Conversely, impaired HPA axis also leads to concurrent independent body fat gain (84), as multiple mechanisms mediated by the HPA axis induce increase of fat cell size and induce a pro-inflammatory status irrespective of caloric balance, proportion of macronutrient intake, and sleeping patterns, since a post-receptor modification from cortisone to cortisol by enhanced activity of 11betahydroxysteroid dehydrogenase type 1(11beta-HSD1) (90,91). In addition,disruption of the muscle metabolism, herein induced by altered cortisol regulation, has also demonstrated to have direct effects on the metabolism and accumulation of fat (92).…”

“…Since the HPA axis is chronically and more severely enhanced by high tension levels, more than any other mood state, it would be expected, from this perspective, to find negative correlations between tension levels and body composition. Indeed, higher tension, which have been correlated with impaired hydration and fat oxidation, muscle catabolism, and increased body fat, are possibly due to the harmful metabolic effects of the chronic stimulation of the HPA axis (82)(83)(84)(85), although direct effects of tension, depression, and anger on increased body fat has been observed (86). In additional, overall mood states can hypothetically be indirect signals of hydration status, although direct relationships are unlikely.…”

Whey for Sarcopenia; Can Whey Peptides, Hydrolysates or Proteins Play a Beneficial Role?

“…IGF-1 participates in muscle anabolism via Akt phosphorylation activating the mammalian target of rapamycin (mTOR) pathway which ultimately controls muscle protein synthesis and turnover [ 27 ]. Sarcopenia results from a decrease in muscle anabolic pathways with an increase in catabolic pathways [ 28 ]. For sarcopenic individuals, Kwak et al [ 21 ] observed a significant (further) decrease in serum IGF-1 from 72.61 ± 5.49 ng/mL to 58.16 ± 3.37 ng/mL compared to the non-sarcopenic control group of similar age.…”

Sonoelastography to Assess Muscular Stiffness Among Older Adults and its Use for the Diagnosis of Sarcopenia: A Systematic Review

“…Sarcopenia is mainly caused by structural changes, such as loss of muscle fibers and reduction in their size, lower ratio of fast (type II) to slow (type I) muscle fibers, adipose and fibrotic tissue infiltrations [8][9][10], and muscular mass loss, that occur with aging. The process may be accelerated and worsened by a sedentary lifestyle, poor nutritional status [11], and chronic diseases that cause inflammation [12] along with hormonal and metabolic dysregulations [13].…”