Digital Phenotyping of Rest-Activity Rhythms and Biological Aging from Longitudinal Monitoring with Commercial Wearable Devices in All of Us

ABSTRACT Poor circadian health is increasingly recognized as a determinant of aging and chronic diseases, yet longitudinal evidence in free-living populations remains limited. Most prior studies have been restricted to cross-sectional designs or short 7-day monitoring, precluding insight into long-term aging dynamics. To address this gap, we analyzed multi-year consumer wearable data linked with electronic health records from the All of Us Research Program to evaluate circadian rest-activity rhythms as longitudinal predictors of biological aging. Among 2,222 participants (median age 60.6 years, 68.5% female) contributing 8,447 person-years of Fitbit activity data with annual biological age estimates (PhenoAge), we performed high-dimensional digital phenotyping integrating functional data analysis with conventional rhythm metrics. Higher rhythm intensity reduced the odds of accelerated aging by 26-46%, greater regularity lowered the odds by 9-13%, whereas delayed acrophase increased the odds by 22%. Sex-stratified analyses revealed universal protection from rhythm intensity in both sexes, but stronger timing- and regularity-related vulnerabilities to accelerated aging in females (12-18% higher odds). In contrast, males exhibited a biphasic instability phenotype, characterized by early-morning surges and late-evening rebounds, uniquely linked to accelerated aging. This study provides the first large-scale longitudinal evidence establishing circadian rest-activity rhythms derived from consumer wearables as digital biomarkers of aging trajectories. With the growing scalability and ubiquity of consumer devices, our findings pave the way toward scalable aging risk assessment, targeted interventions, and advancing digital precision medicine to promote healthy longevity at the population level. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study received no funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The All of Us Research Program conducted data collection under centralized Institutional Review Board (IRB) approval, with informed consent obtained from participants. De-identified data are available through the All of Us Research Workbench upon approval of the research proposal. In accordance with the All of Us Data and Statistics Dissemination Policy, no results with cell sizes ≤20 observations are reported. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data supporting the results in this study are available for approved researchers following registration, completion of ethics training, and attestation of a data use agreement through the All of Us Research Workbench platform.