The detrimental impacts of cumulative obesity exposures and their interactions with genetics on biological aging remain poorly understood. We included 687 older adults (median age: 79.6 years) from the Rugao Longitudinal Ageing Study (RLAS), a community-based cohort study conducted in Rugao, Jiangsu, China. The cumulative exposures of body mass index (cBMI) and waist circumference (cWC) were calculated as the excessive exposure of BMI and WC relative to their reference values (BMI ≥ 24 kg/m2; WC ≥ 90 cm for males and ≥ 80 cm for females) multiplied by their durations across the 2014, 2017, and 2019 waves. Two biological aging metrics were assessed at the 2021 wave, comprising Klemera and Doubal method-biological age (KDM-BA) and physiological dysregulation (PD). The general linear regression models were performed. We found that both cBMI and cWC were positively associated with KDM-BA and PD in Chinese older adults. In contrast, baseline obesity status showed positive associations only with KDM-BA, but not with PD. Furthermore, we observed a potential modifying effect of genetic susceptibility to longevity on the associations between cWC and KDM-BA, with more pronounced associations among participants with a low polygenic risk score for longevity. The findings suggest the potential importance of long-term obesity management in support of healthier aging trajectories even in later life, particularly for older adults with low genetic susceptibility to longevity. Moreover, our findings may inform future risk stratification strategies that incorporate genetic background, thereby helping identify individuals who may be at relatively higher risk of accelerated aging.
