Circulating Dehydroepiandrosterone and Testosterone are Differentially Associated with Motor Unit Function in Young and Masters Athletes

Abstract

Background Age-related neuromuscular decrements are partly attributed to the gradual decline of circulating sex hormones, accompanied by the transition of metabolic processes from largely anabolic to catabolic, which is further mediated by levels of physical activity [1, 2]. Administration of androgens have been demonstrated to positively influence processes of neuroplasticity in animal models [3, 4], acting both centrally and peripherally. However, human data on the associations of circulating hormone levels with peripheral motor nerve function are scant. The aim of this study was to determine associations of dehydroepiandrosterone (DHEA) and testosterone (T) with motor unit (MU) characteristics in human vastus lateralis (VL), and to investigate the influences of ageing and athletic status. Methods 75 men were studied based on age (young: 20-35yrs; old: 61-81yrs) and competitive athletic status (control, endurance and power). Blood concentrations of DHEA and T were quantified using liquid chromatography mass spectrometry. Intramuscular electromyographic signals were recorded from VL during 25% maximum isometric contractions and decomposed to extract motor unit firing rate (MU FR), and motor unit potential (MUP) duration, and complexity (number of turns). Multi-level mixed effects linear regression models were performed to explore the effects of age and athletic status. Significance was assumed when p < 0.05. Results After adjusting for athletic status, MU FR was positively associated with DHEA levels in both young (β [95% CI]: 0.06 [0.001 to 0.11], p=0.046) and old (0.15 [0.02 to 0.27], p=0.02). Higher T was associated with shorter MUP duration in all young (-0.01 [-0.19 to -0.01], p=0.03) and lower complexity in all old (-0.04 [-0.08 to -0.004], p=0.03); these relationships remained significant after adjusting for athletic status. Conclusions DHEA has established neuroprotective effects which improve strength in frailty [5], possibly mediated by MU FR as shown in all ages here. Young males with higher levels of T exhibited shorter MUP duration, indicating reduced electrophysiological temporal dispersion across MU fibres. In old, higher T levels were associated with reduced MUP complexity, also indicating reduced electrophysiological temporal dispersion across MU fibres. In both cases, this is related to reduced differences in conduction times along axonal branches and/or MU fibres. Although evident in males only, this work highlights the potential of hormone administration as a therapeutic interventional strategy specifically targeting the human neuromuscular systems in older age.