Combined Endurance and Resistance Exercise Mitigates Age-Associated Cardiac Dysfunction

Area of Science:

• Cardiology
• Gerontology
• Molecular Biology

Background:

• Aging leads to cardiac function decline and increased cardiovascular disease risk.
• Exercise is a known strategy to mitigate cardiovascular risks.
• The specific benefits of combined endurance and resistance exercise on cardiac aging are not fully understood.

Purpose of the Study:

• To investigate the effects of combined endurance and resistance exercise on cardiac function in aged mice.
• To identify molecular mechanisms underlying exercise-induced cardioprotection in late life.
• To explore the role of Upstream stimulatory factor 2 (Usf2) in mitigating age-related cardiac dysfunction.

Main Methods:

• Aged mice (22 months old) underwent a combined exercise program (swimming and resistance running).
• Transcriptome analysis was performed on cardiac tissue.
• Cardiac function, pathological hypertrophy, oxidative stress, and senescence were assessed.
• In vitro studies using human cardiomyocytes investigated the role of Usf2.

Main Results:

• Combined exercise training improved cardiac function and mitigated age-associated pathological cardiac hypertrophy, oxidative stress, and senescence in aged mice.
• Transcriptome analysis revealed activation of pathways related to cardiac muscle contraction, mitophagy, and longevity regulation.
• Upstream stimulatory factor 2 (Usf2) was upregulated in response to exercise.
• Overexpression of Usf2 demonstrated anti-senescence effects in human cardiomyocytes, while knockdown exacerbated senescence.

Conclusions:

• Combined endurance and resistance exercise effectively combats age-related cardiac remodeling and dysfunction in late life.
• The cardioprotective effects are associated with the activation of Usf2 and its anti-senescence properties.
• Usf2 presents a potential novel therapeutic target for age-related cardiac dysfunction.