The Divergent Effects of Nicotinamide Riboside and High-Intensity Exercise Training on Skeletal Muscle Epigenetic...

Area of Science:

• Gerontology
• Molecular Biology
• Exercise Physiology

Background:

• Aging involves physiological decline, mitochondrial dysfunction, and epigenetic alterations.
• Nicotinamide riboside (NR) and high-intensity interval training (HIIT) may counter aging, but their impact on skeletal muscle epigenetic aging is unclear.

Purpose of the Study:

• To investigate the effects of NR supplementation and HIIT on epigenetic age acceleration (EAA) in human skeletal muscle.
• To explore the relationship between mitochondrial content and EAA following these interventions.

Main Methods:

• Analysis of skeletal muscle samples from three independent studies.
• Assessment of EAA using seven epigenetic clocks after 5-month NR supplementation and 4-6 week HIIT.
• Correlation analysis between mitochondrial content changes and EAA.

Main Results:

• NR supplementation was linked to reduced muscle EAA, particularly with PCHannum, MEAT, and DunedinPACE clocks.
• HIIT showed opposing effects, increasing the pace of aging according to the DunedinPACE clock.
• Changes in skeletal muscle mitochondrial content correlated with MEAT-derived EAA changes after NR and 6 weeks of HIIT.

Conclusions:

• Skeletal muscle epigenetic aging can be modulated by NR and HIIT, but in opposite directions.
• Mitochondrial abundance may be linked to epigenetic aging clocks.
• Further research is needed to understand NR and exercise's regulation of epigenetic aging for healthy aging strategies.