Redox regulation in aging muscles: exercise as a key modulator to combat sarcopenia and frailty

TL;DR

Exercise helps reduce oxidative stress in aging muscles, improving muscle function and reducing frailty in older adults.

Contribution

This review highlights exercise as a key modulator of redox balance in aging muscles, offering insights into molecular pathways and intervention effects.

Findings

Aerobic and resistance exercises reduce oxidant markers and enhance antioxidant levels in older adults.

Multicomponent exercise programs improve muscle strength and reduce frailty scores in randomized trials.

Exercise activates pathways like Nrf2, AMPK, and PGC-1α to combat oxidative stress in aging muscles.

Abstract

Aging is characterized by progressive decline in skeletal muscle function, which can lead to sarcopenia (loss of muscle mass and strength) and frailty (increased vulnerability to stressors), with oxidative stress—arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—playing a central role. This narrative review synthesizes evidence on how exercise modulates redox homeostasis to mitigate these conditions in older adults.

To explore the sources and consequences of oxidative stress in aging muscle, examine exercise’s role in restoring redox balance, evaluate its impact on sarcopenia and frailty, and identify relevant biomarkers and future research directions. We achieve this by exploring key sources through representative studies, examining molecular mechanisms via pathway analyses, evaluating intervention effects using RCTs and meta-analyses, and identifying biomarkers and gaps through critical synthesis.

This narrative review involved a comprehensive literature search in databases such as PubMed, Web of Science, and Scopus, focusing on studies from 2000 to 2025 on oxidative stress, exercise, sarcopenia, and frailty in adults aged 60+. Inclusion criteria prioritized peer-reviewed articles, meta-analyses, and RCTs; exclusion applied to non-English or irrelevant studies. Over 100 articles were selected qualitatively for synthesis.

Aerobic and resistance exercises reduce oxidant markers (e.g., MDA decreased by 10%–20% in meta-analyses) and enhance antioxidants (e.g., SOD increased by 15%–30%), upregulating pathways like Nrf2, AMPK, and PGC-1α. Multicomponent programs improve muscle strength (e.g., 20%–40% gains in RCTs) and frailty scores (e.g., reductions in Fried Frailty Phenotype by 1–2 points). However, heterogeneous responses exist, with some studies showing neutral effects on certain markers.

Exercise emerges as a non-pharmacological intervention to attenuate oxidative stress-driven muscle aging, promoting healthy aging. Future studies should focus on personalized regimens and long-term biomarkers for clinical translation.

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