Volume 83, December 2023, 102127Author links open overlay panel,

Reduced muscle strength and mass is one of the hallmarks of physiological aging in humans and can result in severe impairment of the quality of life. In part this is caused by a functional loss of the highly specialized muscle stem cells (MuSCs), which in healthy conditions provide maintenance, growth, and regeneration. Recent progress in understanding of the stem cell niche and results from single cell technologies reveal exciting insights at unprecedented detail into MuSCs and muscle biology during aging. Here, we review this field and discuss the implications of current findings with a focus on cellular reprogramming approaches as a novel therapeutic avenue for age-related muscle decline.

Section snippetsThe role of muscle stem cells for muscle function

The muscle tissues are critical for respiration, locomotion, organismal metabolism, and many other crucial physiological functions. In healthy humans, muscle forms the largest tissue by weight. Its share of the total body mass gradually declines with increasing age at an annual rate of around 1–2% for people 50 years and older [1]. This dispersed atrophy, termed sarcopenia, results in loss of muscle strength, frailty, restricted mobility, and accounts for an estimated hospitalization cost of

Muscle stem cells lose function during aging

During human aging, the muscle mass declines rapidly, and regeneration is impaired, ultimately resulting in weakness, longer recovery times from injury, and muscle fibrosis, all of which affect eventually all of the elderly population. The overall loss of muscle volume is primarily attributed to the atrophy and loss of individual muscle fibers and secondary to insufficient regeneration of physiologically deteriorating tissue. At least in part, this is due to functional impairment of MuSCs. This

Therapeutic avenues to young muscles

Muscle injury and degeneration due to prolonged immobilization is common in the elderly, therefore age-associated loss of muscle function and regeneration is an important therapeutical goal. Attempts to reduce the biological age, that is, to rejuvenate MuSCs, are particularly interesting since restoring the function of this specific, relatively small number of cells has the potential to result in widespread muscle improvement. This is observed in the drug-free interventions calorie-restriction

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: the authors are employees of Altos Labs.

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