Fight Aging!

Researchers have implicated numerous mechanisms in the age-related loss of muscle mass and strength leading to the condition known as sarcopenia. While not everyone arrives at a diagnosis of sarcopenia, everyone is subject to the progressive deterioration of muscle tissue. One of the challenges facing attempts to understand age-related disease in detail is that the noteworthy mechanisms of aging form a complex, interacting web of cause and consequence. It is next to impossible to determine which mechanisms are more or less important from observation alone. So while one can mount a good argument for sarcopenia to be driven by reduced stem cell activity, proving that would require interventions that do not at present exist. One is further left struggling to explain how exactly that loss of stem cell function takes place: which of the mechanisms of aging are most important in driving it?

Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women.

Here, we evaluate how the nine classic hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication contribute to skeletal muscle ageing and the pathophysiology of sarcopenia. We also highlight five novel hallmarks of particular significance to skeletal muscle ageing: inflammation, neural dysfunction, extracellular matrix (ECM) dysfunction, reduced vascular perfusion, and ionic dyshomeostasis, and discuss how the classic and novel hallmarks are interconnected. Their clinical relevance and translational potential are also considered.

We conclude that there is strong evidence for epigenetic alteration, mitochondrial dysfunction, neural dysfunction, and moderate evidence for inflammation, deregulated nutrient sensing, immunoaging, ECM dysfunction, and reduced vascular perfusion as hallmarks for skeletal muscle ageing, with their relevance for sarcopenia evolving.

Link: https://doi.org/10.1042/CS20230319