Sleep chart of biological aging clocks in middle and late life

Optimal sleep plays a vital role in promoting healthy aging and enhancing longevity. This study proposes a Sleep Chart to assess the relationship between sleep duration and 23 biological aging clocks across 17 organ systems or tissues and 3 omics data types (imaging, proteomics, and metabolomics). First, a systemic, U-shaped pattern shows that both short (<6 hours) and long (>8 hours) sleep duration are linked to elevated biological age gaps (BAGs) across 9 brain and body systems and 3 omics types, with optimal sleep time varying by organ and sex ([6.4-7.8] hours). Furthermore, short and long sleep duration, compared to a normal sleep duration ([6-8] hours), are consistently linked to increased risk of systemic diseases beyond the brain and all-cause mortality, with evidence from genetic correlations and time to incident disease predictions, such as migraine, depression, and diabetes. Finally, short and long sleep duration are associated with late-life depression via distinct pathways: long sleep may contribute indirectly through biological aging processes, while short sleep shows a more direct link. Although our Mendelian randomization does not show strong causal effects from disease to sleep disturbances, it does not fully rule out the possibility that sleep disturbances may, in part, reflect underlying disease burden. Our findings suggest that the U-shaped relationship is likely driven by modifiable sleep disturbances rather than genetic predisposition, highlighting the potential of sleep optimization to support healthy aging, lower disease risk, and extend longevity. An interactive web portal is available to explore the Sleep Chart at: https://labs-laboratory.com/sleepchart.