Key result
Rising SASP biomarkers predict worse physical recovery in older ADHF patients, including a ~1.8-point lower SPPB.
Why the study?
Cellular senescence has been implicated in heart failure pathophysiology and functional decline via the pro-inflammatory senescence-associated secretory phenotype (SASP). This study evaluated the association between SASP and physical function in older adults hospitalized for ADHF.
Are higher levels of senescence-associated secretory phenotype (SASP) biomarkers associated with poorer physical function and recovery in older adults hospitalized for acute decompensated heart failure?
RCT (n=226)
Randomized
Are higher levels of senescence-associated secretory phenotype (SASP) biomarkers associated with poorer physical function and recovery in older adults hospitalized for acute decompensated heart failure?
Answers are grounded in this paper and cite their sources.
Higher and increasing levels of pro-inflammatory senescence-associated secretory phenotype (SASP) biomarkers are associated with poorer baseline physical function and impaired functional recovery at 3 months in older adults hospitalized for acute decompensated heart failure.
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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Semelka et al. (2026) conducted an RCT in Acute decompensated heart failure (ADHF) (n=226). Senescence-associated secretory phenotype (SASP) biomarkers (18-analyte panel) / physical rehabilitation intervention vs. Attention control / lower SASP biomarker levels was evaluated on Change in Short Physical Performance Battery (ΔSPPB) and 6-minute walk distance (Δ6MWD) at 3 months (MD -1.80 for ΔSPPB, 95% CI -2.58 to -1.03, p=<0.001). Increasing SASP biomarker levels over 3 months predicted reduced physical function recovery in older ADHF patients (ΔSPPB -1.80, 95% CI -2.58 to -1.03, p<0.001; Δ6MWD -49.7 m, p=0.001).
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