Abstract Introduction Rest-activity circadian rhythms (RARs) play a crucial role in health. Disrupted rhythms may increase mortality risk, yet the underlying mechanisms remain elusive. Purpose This study was aimed to examine the associations of rest-activity rhythms with all-cause and cardiovascular mortality and explore the potential mediating role of biological ageing. Methods This study included a cohort of 6,706 adults from the 2011–2014 US National Health and Nutrition Examination Survey. Participants wore a wrist actigraph (ActiGraph GT3X+) to estimate RAR parameters, including relative amplitude (RA), interdaily stability (IS), intradaily variability (IV), least active 5-hour period (L5), and most active 10-hour period (M10). Participants were grouped into three categories according to their levels of RAR parameters. Survey-weighted Cox proportional hazards models were used to assess associations of RARs with all-cause and cardiovascular mortality. Survey-weighted linear regression models were used to evaluate the correlations between RARs and biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). Besides, we analyzed the potential intermediary role of biological ageing markers. Results Over a median follow-up of 6.75 years, 522 all-cause deaths and 134 cardiovascular deaths were recorded. Participants in the highest tertile of RA (stronger circadian rhythmicity) had 49% to 61% lower all-cause and cardiovascular mortality compared to those in the lowest tertile (p0.05). Greater IS (more stable sleep-wake cycles) was associated with a 33% reduction in all-cause mortality (p 0.01) but was not significant for cardiovascular mortality. Higher M10 (greater daytime activity) was linked to 53% to 67% lower risks (p0.01). However, higher L5 (greater nighttime activity) and higher IV (fragmented rhythm and inefficient sleep) were strongly associated with elevated mortality risk (p 0.05). Notably, the strongest associations with all-cause and cardiovascular mortality were for relative amplitude, a key indicator of overall circadian rhythmicity, and M10, which reflects physical activity levels. Participants with disrupted rest-activity rhythms exhibited accelerated biological ageing, which were associated with increased mortality risk. Mediation analyses demonstrated that PhenoAge explained 8.72% (p 0.001) and 16.06% (p 0.001) of the association between RA and all-cause and cardiovascular mortality, respectively. BioAge mediated 2.08% (p = 0.002) and 4.97% (p 0.001), respectively. Conclusions Weakened and disrupted rest-activity rhythms are related to higher all-cause and cardiovascular mortality. Biological ageing partially mediates these associations, highlighting the need for interventions targeting both circadian rhythms and ageing processes to reduce mortality risk.
Gu et al. (2025) studied this question.