How Aging Cells Harm Heart Fluid Drainage and May Contribute to Heart Failure with Normal Pumping Function

Cellular senescence may impair cardiac lymphatic function, contributing to heart failure with preserved ejection fraction (HFpEF).

• The senescence-associated secretory phenotype could exacerbate myocardial interstitial edema and chronic inflammation in HFpEF.
• Lymphatic endothelial dysfunction is proposed as a significant factor in the pathobiology of HFpEF.
• Emerging evidence from molecular geroscience and lymphatic biology supports this novel mechanistic framework.
• Potential therapeutic approaches include senolytic and senomorphic interventions targeting cellular senescence.
• Challenges exist in cardiac lymphatic imaging and drug delivery, particularly in elderly patients with comorbidities.

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