Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline

Abstract

In the United Kingdom (UK), it is projected that by 2035 people aged >65 years will make up 23 % of the population, with those aged >85 years accounting for 5% of the total population. Ageing is associated with progressive changes in muscle metabolism and a decline in functional capacity, leading to a loss of independence. Muscle metabolic changes associated with ageing have been linked to alterations in muscle architecture and declines in muscle mass and insulin sensitivity. However, the biological features often attributed to muscle ageing are also seen in controlled studies of physical inactivity (e.g. reduced step-count and bed-rest), and it is currently unclear how many of these ageing features are due to ageing per se or sedentarism. This is particularly relevant at a time of home confinements reducing physical activity levels during the Covid-19 pandemic. Current knowledge gaps include the relative contribution that physical inactivity plays in the development of many of the negative features associated with muscle decline in older age. Similarly, data demonstrating positive effects of government recommended physical activity guidelines on muscle health are largely non-existent. It is imperative therefore that research examining interactions between ageing, physical activity and muscle mass and metabolic health is prioritised so that it can inform on the "normal" muscle ageing process and on strategies for improving health span and well-being. This review will focus on important changes in muscle architecture and metabolism that accompany ageing and highlight the likely contribution of physical inactivity to these changes.

Keywords: Ageing; Metabolism; Muscle; Physical inactivity; Sarcopenia.

Fig. 1

A theoretical construct outlining the relationship between physical inactivity levels and muscle metabolic health. It is proposed exercise will produce significant physiological stress on muscle to produce positive gains in muscle strength, protein synthesis and insulin sensitivity, but this exercise stress will be relatively short lived. In comparison, physical inactivity will impose opposing physiological signals of smaller magnitude, but these signals will persist for considerably longer durations in sedentary individuals and will induce muscle level adaptations that persist as long as inactivity is present resulting in relatively quick (hours to days) negative adaptation.

Fig. 2

Models of inactivity/immobilisation against the spectrum of physical activity. DI = dry water immersion, ULLS = unilateral lower limb suspension, WHO = World Health Organisation.