Sarcopenia is the name given to the advanced stage of loss of muscle mass and strength, a phenomenon that occurs universally with age, but more rapidly in some people than in others. It is certainly the case that lack of exercise and fitness in later life is problematic, and the cause of a sizable fraction of the problem. Nonetheless, there are mechanisms of degeneration that exercise can only slow, and which will lead to frailty in the end, given enough time alive.
Many potential causes of sarcopenia have a decent amount of supporting evidence. Those that look the most compelling at the present time are defects in the processing of dietary leucine, age-related stem cell dysfunction, the disruption to tissue maintenance caused by chronic inflammation, and molecular damage in the neuromuscular junctions linking the nervous system to muscles. That latter line item is the favored explanation in this open access paper.
We here review the loss of muscle function and mass (sarcopenia) in the framework of human healthspan and lifespan, and mechanisms involved in aging. The rapidly changing composition of the human population will impact the incidence and the prevalence of aging-induced disorders such as sarcopenia and, henceforth, efforts to narrow the gap between healthspan and lifespan should have top priority.
There are substantial knowledge gaps in our understanding of aging. Heritability is estimated to account for only 25% of lifespan length. However, as we push the expected lifespan at birth toward those that we consider long-lived, the genetics of aging may become increasingly important. Linkage studies of genetic polymorphisms to both the susceptibility and aggressiveness of sarcopenia are still missing. Such information is needed to shed light on the large variability in clinical outcomes between individuals and why some respond to interventions while others do not.
We here make a case for the concept that sarcopenia has a neurogenic origin and that in manifest sarcopenia, nerve and myofibers enter into a vicious cycle that will escalate the disease progression. We point to gaps in knowledge, for example the crosstalk between the motor axon, terminal Schwann cell, and myofiber in the denervation processes that leads to a loss of motor units and muscle weakness. Further, we argue that the operational definition of sarcopenia should be complemented with dynamic metrics that, along with validated biomarkers, may facilitate early preclinical diagnosis of individuals vulnerable to develop advanced sarcopenia.