Frailty-specific dose-response relationships between physical activity and all-cause mortality: Longitudinal observational study combining accelerometry data

Background: Physical activity (PA) is inversely associated with all-cause mortality, yet how frailty status shapes the accumulation and saturation of this benefit remains unclear. This study aimed to assess frailty-specific associations between physical activity and all-cause mortality, characterize marginal benefits and benefit saturation across frailty strata, and identify high-benefit accelerometer-derived activity ranges linked to lower mortality risk. Methods: This prospective cohort study included 90,573 UK Biobank participants with valid 7-day wrist-worn accelerometer data. Light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were quantified, and participants were classified as frail (n = 1631), pre-frail (n = 30,280), or robust (n = 58,662). Restricted cubic spline models and Cox proportional hazards models were used to characterize frailty-specific dose-response associations with all-cause mortality. Results: Frail individuals experienced steeper relative risk reductions at lower PA levels, accompanied by earlier saturation of benefit, whereas robust individuals required higher activity volumes to achieve more modest benefit. The high-benefit LPA range was 1700–2100 min/week in frail individuals (65%–70% lower mortality risk), 1600–2200 min/week in pre-frail individuals (50%–60% lower risk), and 1800–2300 min/week in robust individuals (40%-50% lower risk). Corresponding high-benefit MVPA ranges were 240–500, 220–700, and 260–770 min/week, associated with 70%-80%, 40%-70%, and 30%-60% lower mortality risk, respectively. Conclusions: Frailty modifies how PA-related mortality benefits accumulate and plateau, while preserving the overall inverse association between PA and mortality. These findings highlight the importance of frailty-aware interpretation of accelerometer-derived PA metrics in physiologically vulnerable populations.