Circulating SASP biomarker panel and all-cause mortality in community-dwelling older adults - A Systematic Review and Meta-Analysis of prospective cohort studies

This registration aims to systematically synthesize and quantitatively evaluate the association between circulating senescence-associated secretory phenotype (SASP) biomarkers and all-cause mortality among community-dwelling older adults. Cellular senescence has emerged as a fundamental biological process implicated in ageing and age-related morbidity, with SASP biomarkers representing measurable indicators of senescent cell burden and systemic biological ageing. Although individual prospective cohort studies have explored associations between circulating SASP-related biomarkers and mortality outcomes, findings remain heterogeneous and lack comprehensive synthesis. This systematic review and meta-analysis will identify and include prospective cohort studies evaluating circulating SASP biomarker panels measured in blood-based samples (e.g., serum, plasma, or other circulating specimens) among community-dwelling older adult populations. Eligible studies will report associations between baseline circulating SASP biomarkers and subsequent all-cause mortality outcomes over longitudinal follow-up periods. The review will systematically search major electronic databases, perform study selection according to predefined eligibility criteria, extract study characteristics and outcome data using standardized forms, and assess methodological quality and risk of bias using appropriate appraisal tools for observational studies. Where sufficient homogeneity exists, pooled effect estimates will be generated using meta-analytic methods. Heterogeneity, publication bias, and subgroup analyses will be explored where feasible. Potential sources of variability, including participant characteristics, biomarker composition, follow-up duration, geographic region, and analytical adjustments, will also be examined. The primary outcome will be all-cause mortality. Secondary objectives include evaluating the prognostic performance of individual SASP biomarkers and biomarker panels, exploring dose-response relationships where data permit, and identifying factors influencing observed associations. The expected outcome of this study is to provide consolidated evidence on whether circulating SASP biomarker panels can serve as reliable prognostic indicators of mortality risk in older adults living in the community. Findings may contribute to improving biological ageing assessment, informing geriatric risk stratification, and guiding future translational research on ageing-related biomarkers and preventive health strategies.