Impaired proteostasis during skeletal muscle aging

Area of Science:

• Gerontology and cellular biology
• Skeletal muscle physiology

Background:

• Aging leads to detrimental effects on tissue homeostasis, particularly skeletal muscle.
• Skeletal muscle aging involves functional impairment and mass loss, linked to proteostasis network disruption.
• Oxidative stress contributes to protein aggregate accumulation, indicating ubiquitin-proteasomal system (UPS) and autophagy-lysosomal system (ALS) dysregulation.

Purpose of the Study:

• To review the connection between proteostasis loss and skeletal muscle functional decline during aging.
• To explore the role of redox regulation in skeletal muscle aging.
• To enhance understanding of skeletal muscle aging mechanisms.

Main Methods:

• Literature review of current knowledge on proteostasis, redox regulation, and skeletal muscle aging.
• Analysis of the interplay between UPS, ALS, oxidative stress, and muscle function.
• Synthesis of findings to elucidate aging-related molecular pathways.

Main Results:

• Aging disrupts the ubiquitin-proteasomal system (UPS) and autophagy-lysosomal system (ALS), key for protein and organelle clearance.
• Accumulation of protein aggregates, driven by oxidative stress, is a hallmark of aging-related proteostasis loss.
• Redox regulation significantly impacts skeletal muscle function and maintenance during the aging process.

Conclusions:

• Loss of proteostasis, particularly UPS and ALS dysfunction, is central to skeletal muscle aging.
• Redox regulation plays a critical role in modulating skeletal muscle aging.
• Understanding these mechanisms is vital for addressing age-related muscle decline.