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, r² = 0.053), grip strength positively with activin A (P = 0.046, r² = 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.

Keywords: Aging; GDF11; GDF8; frailty; myostatin.

Figure 1

GDF11 ELISA antibody does not detect recombinant myostatin in a physiological or supra‐physiological range. Concentration of GDF11 (0–2000 pg/mL) and myostatin (0–20,000 pg/mL) as a function of absorbance (450–570 nm). Samples run in triplicate and reported here as mean with standard error. Solid line indicates linear regression for GDF11, dashed line for myostatin.

Figure 2

Peptide concentration (pg/mL) as a function of age (years), grip strength (kg) and 6‐min walk performance (m). (A–E) Age (years), (F–J) Grip strength, (K–O) 6‐min walk distance covered (m), as a function of concentration of total myostatin (top row), free myostatin (second row), FLRG (middle row), GDF11 (forth row), and activin A (bottom row). All concentrations in pg/mL.

Figure 3

Prediction of aging factors as a function of actual factor. (A) Predicted age (years) as a function of age (years). (B) Predicted grip (kg) as a function of grip (kg). (C) Predicted 6MWT distance (m) as a function of 6MWT distance (m).