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This study is the second of two studies aimed at using an untargeted approach to identify metabolomic markers associated with rest-activity rhythm characteristics and focuses on older women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The analysis included 688 women in the Women\u2019s Health Initiative. Rest-activity rhythms were characterized by parametric and non-parametric algorithms applied to accelerometry data. Metabolomics data were measured from fasting serum samples with ultra high-performance liquid-phase chromatography and gas chromatography coupled with mass spectrometry and tandem mass spectrometry. Associations between rest-activity rhythms and metabolomics were determined by multiple linear regression models and Ingenuity Pathway Analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 934 metabolites included, 280 showed an association (false discovery rate\u2009&amp;lt; 0.1) with one of the three primary rest-activity variables (pseudo F-statistic, intradaily variability, and interdaily stability). These metabolites represent a wide range of biochemical classes and metabolic pathways, including sulfur amino acids, fibrinopeptides, plasmalogens, amino sugar metabolites, and nucleotides. The PEX5 gene network was identified by the Ingenuity Pathway Analysis as the most significantly enriched genetic pathway in relation to rest-activity rhythms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found numerous metabolites and pathways that were associated with rest-activity rhythm variables in older women, suggesting a potentially wide-reaching role of diurnal behaviors in human metabolism and health.<\/jats:p>\n                    <jats:p>Statement of Significance In this metabolomics study in older women, we found a large number of metabolites that were associated with rest-activity rhythms. These metabolites represented a wide range of biochemical classes and metabolic pathways. This analysis also confirmed numerous metabolite associations we have recently found in a sample of older men in the Osteoporotic Fractures in Men study, lending further support to a wide-reaching role of circadian rhythms and diurnal behaviors in human health. To the best of our knowledge, our two studies were the first metabolomics investigations focusing on rest-activity rhythm characteristics. With further validation studies, we anticipate that findings from these studies will contribute to the broader endeavor to understand, diagnose, and treat circadian rhythm-related disorders, with potential benefits for human health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/sleep\/zsaf320","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:09:09Z","timestamp":1760011749000},"source":"Crossref","is-referenced-by-count":4,"title":["Metabolomic biomarkers of rest-activity rhythms in older women: results from the Women\u2019s Health Initiative study"],"prefix":"10.1093","volume":"49","author":[{"given":"Lingxiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health , New Haven, CT ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2753-1728","authenticated-orcid":false,"given":"Chris Ho Ching","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Texas Health Sciences Center , Houston, TX ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung A Viola","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health , New Haven, CT ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aladdin H","family":"Shadyab","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human Longevity Science and Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego , La Jolla, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-976X","authenticated-orcid":false,"given":"Andrea","family":"LaCroix","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human Longevity Science and Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego , La Jolla, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L","family":"Stone","sequence":"additional","affiliation":[{"name":"California Pacific Medical Center Research Institute , San Francisco, CA ,","place":["United States"]},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Neurology and Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-3513","authenticated-orcid":false,"given":"Kathleen M","family":"Hayden","sequence":"additional","affiliation":[{"name":"Department of Social Sciences and Health Policy, Wake Forest University School of Medicine , Winston-Salem, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Casanova","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine , Winston-Salem, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Behavioral Medicine, Wake Forest University School of Medicine , Winston-Salem, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu-Chiuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Southern California, Keck School of Medicine , Los Angeles, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine , Winston-Salem, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E","family":"Manson","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Division of Preventive Medicine, Harvard Medical Scho,ol, and Harvard T.H. 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