Aging-related loss of muscle mass, a biological process named
sarcopenia, contributes to mobility impairment, falls, and physical
frailty, resulting in an impaired quality of life in older people. In view of the aging of our society, understanding the underlying mechanisms of
sarcopenia is a major health-care imperative. Evidence obtained from human and rodent studies demonstrates that skeletal muscle
denervation/reinnervation cycles occur with aging, and that progressive failure of myofiber reinnervation is a major cause of the accelerating phase of
sarcopenia in advanced age. However, the mechanisms responsible for the loss of myofiber innervation with aging remain unknown. The two major strategies that counteract
sarcopenia, that is,
caloric restriction and
endurance training, are well known to protect neuromuscular junction (NMJ) integrity, albeit through undefined mechanisms. Interestingly, both of these interventions better preserve PGC-1α expression with aging, a transcriptional coactivator which has recently been shown to regulate key
proteins involved in maintaining NMJ integrity. We therefore propose that the aging-related decline in PGC-1α may be a central mechanism promoting instability of the NMJ and consequently, aging-related alterations of myofiber innervation in
sarcopenia. Similarly, the promotion of PGC-1α expression by both
caloric restriction and exercise training may be fundamental to their protective benefits for aging muscle by better preserving NMJ integrity.