Abstract
BACKGROUND: Frailty is a progressive, dynamic clinical syndrome characterized by reduced physiological reserves and increased vulnerability to stressors, leading to adverse outcomes in older adults. Despite its clinical significance, routine detection of frailty remains challenging owing to subtle presentations and time constraints during assessments. Longitudinal studies are essential for capturing its biological trajectory and identifying early biomarkers. OBJECTIVE: This scoping review aims to systematically identify and map biomarkers-including inflammatory, hormonal, metabolic, genetic, and imaging-based markers-investigated for their longitudinal associations with frailty in older adults. Studies involving older adults with comorbid conditions (eg, cancer, infectious diseases, cardiovascular diseases) will also be included when frailty is assessed as an outcome. METHODS: We will conduct a comprehensive literature search in 6 databases (PubMed, CINAHL, Cochrane Library, Scopus, Web of Science, and Embase). We will include longitudinal studies that examine the association between objectively measured biomarkers and frailty, as assessed with validated tools, in older adults. Studies published in English, Korean, or Chinese will be considered, with no restriction on publication date. RESULTS: We identified 3315 records after duplicate removal in an exploratory search conducted in July 2024, indicating a substantial body of literature for review. We plan to complete this review by December 2026. CONCLUSIONS: This review will identify and describe longitudinal biomarkers that precede frailty in older adults, highlighting their potential for personalized clinical application. Anticipated limitations include reliance on observational study designs, methodological heterogeneity, and limited causal inference. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/83312.