Ageing research reviewsOct 12, 2026

Cell Aging in Heart Failure with Normal Pumping: Causes and Possible Treatments

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 13, 2026

Abstract

Nearly 50% of global heart failure cases are attributed to heart failure with preserved ejection fraction (HFpEF).

HFpEF is recognized as a complex condition linked to aging, cardiometabolic diseases, and chronic low-grade inflammation.
Cellular senescence and the senescence-associated secretory phenotype (SASP) may connect systemic stressors to heart dysfunction.
SASP operates through paracrine and endocrine pathways, potentially creating a self-reinforcing cycle in heart tissue.
The effects of cellular senescence can vary significantly based on context, cell type, and developmental stage.
Current evidence relating senescence to HFpEF is largely preclinical or associative, with limited human-specific data.

Simplified

Heart failure with preserved ejection fraction (HFpEF) contributes to nearly 50% of the global heart failure (HF) cases, and remains a major clinical challenge because of its heterogeneous pathophysiology, substantial residual morbidity, and limited mechanism-based treatment options. HFpEF is increasingly recognized as a heterogeneous multisystem syndrome closely associated with aging, cardiometabolic comorbidities, and chronic low-grade inflammation. Cellular senescence and the senescence-associated secretory phenotype (SASP) have emerged as potential mechanisms linking several of these systemic stressors to cardiovascular dysfunction. By paracrine and endocrine communication, SASP creates a self-reinforcing circuit in the myocardium. However, the biological consequences of cellular senescence are highly context-, cell type-, and stage-dependent, and transient senescence may exert adaptive or tissue-protective effects under certain conditions. Moreover, much of the current evidence linking senescence to HFpEF remains preclinical or associative, and HFpEF-specific human data are still limited. This review systematically assesses the current evidence linking cellular senescence and SASP to HFpEF and examines the therapeutic potential and limitations of senolytics and senomorphics.

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Cell Aging in Heart Failure with Normal Pumping: Causes and Possible Treatments

Abstract

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