Rethinking Muscle Aging Through the Lens of Fibro-Adipogenic Progenitors

Area of Science:

• Muscle biology
• Aging research
• Cellular and molecular mechanisms of aging

Background:

• Skeletal muscle aging involves interstitial adipose and fibrotic tissue deposition, impairing structure and function.
• This maladaptive remodeling compromises muscle performance, regenerative capacity, and contributes to frailty and sarcopenia.
• Fibro-adipogenic progenitors (FAPs) are the primary cellular source of pathological fibrosis and adipogenesis in muscle.

Purpose of the Study:

• To summarize current knowledge on the roles and dynamics of FAPs in aged muscle.
• To discuss FAPs as potential therapeutic targets for rejuvenating aged muscle.
• To understand how aging reprograms FAP fate and function for muscle regeneration.

Main Methods:

• Review of current scientific literature on FAPs in muscle aging.
• Analysis of cellular and molecular mechanisms driving FAP dysfunction.
• Exploration of therapeutic strategies targeting FAPs for muscle rejuvenation.

Main Results:

• In young muscle, FAPs transiently support regeneration; in aged muscle, they promote fibrosis and fat accumulation.
• Aged muscle niches exhibit chronic inflammation, altered matrix, and impaired communication, driving FAP maladaptation.
• FAP dysfunction is a central mechanism in age-related sarcopenia, injury susceptibility, and delayed recovery.

Conclusions:

• Dysfunctional FAPs contribute significantly to age-related muscle decline and sarcopenia.
• Targeting FAP reprogramming offers a promising strategy to restore muscle regenerative capacity.
• Rejuvenating the aged muscle niche by modulating FAPs could mitigate muscle aging effects.