Abstract
Ageing is associated with a progressive loss of skeletal muscle mass, quality and function—sarcopenia, associated with reduced independence and quality of life in older generations. A better understanding of the mechanisms, both genetic and epigenetic, underlying this process would help develop therapeutic interventions to prevent, slow down or reverse muscle wasting associated with ageing. Currently, exercise is the only known effective intervention to delay the progression of sarcopenia. The cellular responses that occur in muscle fibres following exercise provide valuable clues to the molecular mechanisms regulating muscle homoeostasis and potentially the progression of sarcopenia. Redox signalling, as a result of endogenous generation of ROS/RNS in response to muscle contractions, has been identified as a crucial regulator for the adaptive responses to exercise, highlighting the redox environment as a potentially core therapeutic approach to maintain muscle homoeostasis during ageing. Further novel and attractive candidates include the manipulation of microRNA expression. MicroRNAs are potent gene regulators involved in the control of healthy and disease-associated biological processes and their therapeutic potential has been researched in the context of various disorders, including ageing-associated muscle wasting. Finally, we discuss the impact of the circadian clock on the regulation of gene expression in skeletal muscle and whether disruption of the peripheral muscle clock affects sarcopenia and altered responses to exercise. Interventions that include modifying altered redox signalling with age and incorporating genetic mechanisms such as circadian- and microRNA-based gene regulation, may offer potential effective treatments against age-associated sarcopenia.
Highlights
Ageing is a complex multifactorial physiological process involving biochemical and morphological changes at the cellular level that are reflected throughout the organism
The endogenous redox signals generated by contracting skeletal muscle can activate a number of transcription factors with subsequent effects on gene expression and activation of specific cellular pathways
Adaptation and rebuilding of skeletal muscle fibres occurs in response to exercise, whilst muscles of older adults have a blunted response to exercise, often associated with dampened or chronic activation of specific transcription factors
Summary
Ageing is a complex multifactorial physiological process involving biochemical and morphological changes at the cellular level that are reflected throughout the organism. This review discusses the mechanisms regulating disrupted muscle homoeostasis during ageing, focusing on—redox homoeostasis and DNA damage responses, including recent novel developments concerning microRNAs and circadian regulation of gene expression in skeletal muscle and how manipulating these processes could potentially provide a therapeutic opportunity to prevent age-associated sarcopenia. The metabolic and structural changes induced by exercise affect the contractile properties of the muscle fibres and as contracting muscles generate ROS/ RNS, these signalling molecules play crucial roles in the adaptive response to exercise and muscle atrophy during ageing (Table 2, Powers and Jackson 2008). ROS/RNS generate unique signalling cascades that are essential in skeletal muscle contraction and adaptation, and play a role in a wide array of cell processes including cell proliferation, immune response and antioxidant defences. Dysregulated ROS/RNS homoeostasis or signalling responses have been reported in a wide variety of human skeletal muscle disorders, as well as many metabolic diseases including cancers (Mates et al 2008), neurodegeneration (Calabrese et al 2006), obesity (O’Neill et al 2013) and diabetes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
