Middle-aged mice given dasatinib plus quercetin, aerobic exercise, or both for nine months accumulated fewer senescent cardiomyocytes and interstitial cells and retained better myocardial performance and diastolic function than naturally aged controls. Markers of senescence and DNA damage (p16, p21, γ-H2AX) fell at the cellular level, though whole-heart protein expression and the senescence-associated secretory phenotype were unchanged. Exercise alone produced benefits comparable to pharmacological senolysis, with no additive effect from combining the two.
Key Points
- Nine months of senolytics or exercise lowered senescent cardiomyocyte burden
- Diastolic function and myocardial performance preserved in treated aged mice
- Combination offered no additive benefit over either intervention alone
Longevity Analysis
Cardiac aging is driven substantially by cells that persist past their functional lifespan, carrying unresolved DNA damage and impaired mitochondrial output that stiffen the ventricle and blunt relaxation. Removing that interference — pharmacologically or through sustained aerobic loading — preserved contractile and filling capacity over a substantial portion of the lifespan, suggesting the heart's capacity for repair remains responsive well into middle age. That exercise matched the drug intervention, and that neither improved on the other, places the emphasis on consistency of practice rather than escalation of tools.
Original published by Wiley Aging Cell, by Ryan T. Bevington, Amanda L. Johnson, Briana L. Hockey, Val A. Fajardo, Gianni Parise .