Late-life exercise mitigates skeletal muscle epigenetic aging

Area of Science:

• Muscle physiology
• Epigenetics
• Aging research

Background:

• Exercise offers functional benefits for muscle, even in older individuals.
• The role of epigenetic factors in muscle adaptation to late-life exercise is not well understood.

Purpose of the Study:

• To investigate the impact of late-life exercise on epigenetic aging in skeletal muscle.
• To determine if exercise can attenuate age-associated epigenetic changes in muscle.

Main Methods:

• Utilized a murine model of voluntary endurance and resistance exercise (progressive weighted wheel running, PoWeR).
• Employed reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial methylation analysis, and DNAge™ epigenetic aging clock analysis.
• Assessed epigenetic changes in skeletal muscle of old mice (22-24 months) undergoing 8 weeks of PoWeR training.

Main Results:

• Late-life PoWeR training significantly attenuated age-associated promoter hypermethylation in skeletal muscle.
• Muscle from old mice that underwent PoWeR training was epigenetically approximately 8 weeks younger than sedentary controls.
• This epigenetic age reduction represents about 8% of the expected murine lifespan.

Conclusions:

• Exercise, even when initiated late in life, can beneficially impact skeletal muscle epigenetic aging.
• PoWeR training demonstrates a molecular basis for exercise as a potential therapy to mitigate muscle aging.
• These findings support exercise interventions for maintaining skeletal muscle health and function in older populations.