Activin subfamily peptides predict chronological age in humans

Abstract

Loss of muscle mass and function are a well‐defined aspect of human aging from the 3rd decade of life, which result in reduced independence and increased mortality. The activin family of peptides contains several endocrine factors (activin A, myostatin, growth and differentiation factor 11 [GDF11]) that may play roles in changes in muscle mass and the aging process, however, it may be simplistic to consider aging as a result of a single peptides changes. Thus, we aimed to examine changes in activin family members across a cohort of healthy individuals of various ages, hypothesizing that these would aid predictive models of age and functional measures of age. Healthy participants (n = 88) were recruited and resting metabolic rate, body composition, grip strength, walking speed, and circulating plasma concentrations of myostatin (total and free), activin A, follistatin‐like binding protein (FLRG), and GDF11 quantified. Simple regressions between circulating factors and chronological age, grip strength, and walking speed were examined. Multiple stepwise regressions for age, grip strength, and walking speed are also reported. Age negatively correlated with total myostatin (P = 0.032, r 2 = 0.053), grip strength positively with activin A (P = 0.046, r 2 = 0.048), whereas walking speed showed no simple regression relationships. Stepwise regressions suggested a role of total myostatin and activin A in models of age, whereas GDF11 contributed to the model of grip strength. Here we suggest a role for myostatin, activin A, and GDF11 in normal human aging that mirrors animal studies to date. Further interventional studies are required to elicitate the physiological role of these changes in the normal human aging process, and indeed if offsetting these changes can promote successful aging.

Preliminary Investigations Into the Effect of Exercise-Induced Muscle Damage on Systemic Extracellular Vesicle Release in Trained Younger and Older Men

“…Importantly also, in the ageing population, reduced physical activity and increase in sedentary time are typically observed ( Lindsay et al, 2019 ). Furthermore, no difference in muscle mass or fat mass was seen in our study population, unlike that witnessed in wider society ( Volpi et al, 2004 ; Barrios-Silva et al, 2018 ). By studying highly active ageing cohorts, we can separate physiological differences of ageing from inactivity induced changes ( Harridge and Lazarus, 2017 ).…”

Effects of Fortetropin on the Rate of Muscle Protein Synthesis in Older Men and Women: A Randomized, Double-Blinded, Placebo-Controlled Study

“…Although we did not observe any effect on circulating myostatin levels, Fortetropin has been shown to decrease circulating myostatin levels ( 7 , 16 ) in healthy subjects. The consensus of published data suggests an age associated decrease in circulating myostatin levels ( 17 , 18 ), although the role of myostatin in aging has not been established and the functional interpretation of circulating myostatin remains uncertain. We found here that in a group of healthy older subjects, circulating myostatin levels were positively associated with muscle protein FSR.…”

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

“…Similarly, contradictory findings have been made regarding the relationship between serum myostatin and muscle function. Some studies found increased circulating myostatin concentrations in patients with better muscle function or physical performance [ 80 , 81 , 83 , 84 , 87 ], and several indicated such a relationship to be more apparent in the male population [ 85 , 93 ], while others did not show any clear correlation between those parameters [ 82 , 88 , 89 , 92 , 94 ].…”

“…A study of intramuscular mRNA and protein expression showed that although myostatin gene expression was higher in older adults, no difference in myostatin protein content was found [ 74 ]. Results of three studies indicated that serum myostatin concentration rises with age [ 79 , 84 , 94 ]. In their cross-sectional study, Bergen et al, used a new mass spectrometry-based assay to show that circulating myostatin, acting as a homeostatic regulator of muscle mass in males, could be found in the highest concentration in young men, and decreased with age, while in women, it increased as a function of age, acting as a possible mediator of sarcopenia [ 85 ].…”