<p>Optimal sleep has a vital role in promoting healthy ageing and enhancing longevity. Here we propose Sleep Chart to assess the relationship between self-reported sleep duration and 23 biological ageing clocks derived from in vivo imaging<sup><CitationRef CitationID="CR1">1</CitationRef></sup>, plasma proteomics<sup><CitationRef CitationID="CR2">2</CitationRef></sup> and metabolomics<sup><CitationRef CitationID="CR3">3</CitationRef></sup>. First, a systemic, U-shaped pattern emerges between sleep duration and biological age gaps across nine brain and body systems and three omics technologies. The sample-specific lowest biological age gaps are achieved between 6.4 and 7.8 h of sleep duration, varying by organ and sex in the UK Biobank (aged 37–84 years). Furthermore, short (&lt;6 h) and long (&gt;8 h) sleep duration, compared with a normal sleep duration (6–8 h), are associated with increased risk of systemic diseases beyond the brain and all-cause mortality, with evidence from genetic correlations and time-to-incident survival predictions, such as depression and diabetes. Finally, the pathways by which long and short sleep duration are associated with late-life depression differ: ageing clocks may partially mediate the pathway for long sleep duration, while short sleep duration shows a more direct link. Although Mendelian randomization does not provide strong evidence that disease causally affects sleep, it cannot completely exclude such reverse causality. Our findings suggest a cross-organ, multi-omics U-shaped relationship between sleep duration and biological ageing clocks, highlighting the potential of sleep optimization to promote healthy ageing, lower disease risk and extend longevity.</p>

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Sleep chart of biological ageing clocks in middle and late life

  • Cliodhna Kate O’Toole,
  • Zhiyuan Song,
  • Filippos Anagnostakis,
  • Zhijian Yang,
  • Ye Ella Tian,
  • Michael R. Duggan,
  • Chunrui Zou,
  • Yue Leng,
  • Yi Cai,
  • Wenjia Bai,
  • Cynthia H. Y. Fu,
  • Michael S. Rafii,
  • Paul Aisen,
  • Gao Wang,
  • Philip L. De Jager,
  • Jian Zeng,
  • Hamilton Se-Hwee Oh,
  • Xia Zhou,
  • Keenan A. Walker,
  • Daniel W. Belsky,
  • Andrew Zalesky,
  • Eleanor M. Simonsick,
  • Susan M. Resnick,
  • Luigi Ferrucci,
  • Christos Davatzikos,
  • Junhao Wen

摘要

Optimal sleep has a vital role in promoting healthy ageing and enhancing longevity. Here we propose Sleep Chart to assess the relationship between self-reported sleep duration and 23 biological ageing clocks derived from in vivo imaging1, plasma proteomics2 and metabolomics3. First, a systemic, U-shaped pattern emerges between sleep duration and biological age gaps across nine brain and body systems and three omics technologies. The sample-specific lowest biological age gaps are achieved between 6.4 and 7.8 h of sleep duration, varying by organ and sex in the UK Biobank (aged 37–84 years). Furthermore, short (<6 h) and long (>8 h) sleep duration, compared with a normal sleep duration (6–8 h), are associated with increased risk of systemic diseases beyond the brain and all-cause mortality, with evidence from genetic correlations and time-to-incident survival predictions, such as depression and diabetes. Finally, the pathways by which long and short sleep duration are associated with late-life depression differ: ageing clocks may partially mediate the pathway for long sleep duration, while short sleep duration shows a more direct link. Although Mendelian randomization does not provide strong evidence that disease causally affects sleep, it cannot completely exclude such reverse causality. Our findings suggest a cross-organ, multi-omics U-shaped relationship between sleep duration and biological ageing clocks, highlighting the potential of sleep optimization to promote healthy ageing, lower disease risk and extend longevity.