Senescence Biomarkers Predict Physical Function and Clinical Outcomes After Heart Failure Hospitalization: Insights From REHAB-HF

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2026
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Abstract
BACKGROUND: Acute decompensated heart failure (ADHF) is the most common cause of hospitalization in older adults. Cellular senescence, a hallmark of aging biology, has been implicated in heart failure pathophysiology and functional decline via the pro-inflammatory senescence-associated secretory phenotype (SASP). We evaluated the association between SASP and physical function in older adults hospitalized for ADHF. METHODS: REHAB-HF was a trial of older adults hospitalized for ADHF randomized to a novel physical rehabilitation intervention or attention control. We measured a panel of 18-SASP analytes at in-hospital baseline and at 3-month follow-up. Outcomes included short physical performance battery (SPPB) and 6-minute walk distance (6MWD). Statistical analysis included principal component analysis (PCA) of log- and z-transformed SASP values. Associations were evaluated with multivariable regression models adjusted for age, sex, and intervention arm. RESULTS: Samples were available for 226 (65%) of the REHAB-HF participants with mean age (SD) 72.3 (8), 53% female, 52% HFpEF, and 53% assigned to rehab intervention. Principal Component 1 (PC1) reflected a coordinated signal across biomarkers of inflammation and immune signaling. PC1 was associated with poorer function at baseline [(SPPB -0.46 [-0.77, -0.14]; p = 0.004 and 6MWD -19.7 meters [-32.7, -6.7]; p = 0.003)]. Increasing SASP over time was associated with clinically significant reduced physical function improvement (ΔSPPB -1.80 [-2.58, -1.03]; p < 0.001 and Δ6MWD -49.7 meters [-77.2, -22.1]; p = 0.001). CONCLUSION: Higher SASP levels were associated with poorer physical function recovery in older patients hospitalized for ADHF. These findings suggest that inflammatory SASP biomarkers may improve risk stratification and potentially guide therapeutic strategies. REHAB-HF TRIAL IS REGISTERED AT CLINICALTRIALS.GOV CLINICAL TRIAL REGISTRY: NCT02196038.
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Authors Charles Semelka, Molly R Ehrig, Nicholas M. Pajewski, Stephen B. Kritchevsky, Philip Adam Kramer, Anthony E. Peters, Robert John Mentz, Amy M. Pastva, David J. Whellan, Dalane W. Kitzman
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Journal the journals of gerontology series a, biological sciences and medical sciences
Year 2026
DOI
10.1093/gerona/glag256
URL
https://doi.org/10.1093/gerona/glag256
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