UNC45B Reduction With Aging: A Myofiber-Intrinsic Promoting Factor for Sarcopenia

Area of Science:

• Muscle physiology and aging research.
• Molecular mechanisms of muscle function.
• Skeletal muscle biology.

Background:

• Skeletal muscle mass and force decline with aging, with force loss preceding atrophy.
• The precise molecular mechanisms driving age-related muscle decline are not fully understood.
• Uncoordinated mutant number-45 myosin chaperone B (UNC45B) is a myosin co-chaperone with a potential role in muscle regulation.

Purpose of the Study:

• To investigate the role of UNC45B in regulating skeletal muscle mass and force during aging.
• To determine the impact of UNC45B deficiency on muscle function, bone density, metabolism, and behavior.
• To elucidate the mechanisms underlying age-related muscle decline related to UNC45B.

Main Methods:

• Adeno-associated virus-mediated knockdown of Unc45b in mouse triceps surae muscle.
• Generation and analysis of tamoxifen-inducible skeletal muscle-specific Unc45b knockout (Unc45b imKO) mice.
• Assessment of muscle mass, force production, bone mineral density, glucose tolerance, insulin sensitivity, respiratory exchange ratio, sleep patterns, locomotor activity, and body temperature.

Main Results:

• UNC45B expression decreased with age in mouse gastrocnemius muscle.
• Unc45b knockdown reduced muscle force before decreasing muscle mass and lowered bone mineral density.
• Unc45b imKO mice exhibited reduced muscle mass and force, but normal systemic metabolism; however, they showed decreased sleep depth, activity, and body temperature during sleep.

Conclusions:

• UNC45B is essential for maintaining fast-twitch muscle mass and force.
• UNC45B deficiency contributes to muscle atrophy, bone fragility, and impaired sleep quality.
• UNC45B plays a significant role in the physiological changes associated with aging muscle.