Journal article
Metabolomic Biomarkers of Rest-Activity Rhythms in Older Women: Results from the Women's Health Initiative (WHI) Study
Sleep (New York, N.Y.), Vol.49(1), zsaf320
01/13/2026
DOI: 10.1093/sleep/zsaf320
PMCID: PMC12795739
PMID: 41071097
Abstract
Prior research has suggested that disrupted and weakened rest-activity rhythms measured by accelerometry may be associated with risks of many diseases, including cardiometabolic diseases, cancer and dementia but the mechanisms underlying this are not fully understood. 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.
The analysis included 688 women in the Women's 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 (IPA).
Of the 934 metabolites included, 280 showed an association (false discovery rate<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, aminosugar metabolites, and nucleotides. The PEX5 gene network was identified by the IPA as the most significantly enriched genetic pathway in relation to rest-activity rhythms.
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.
Details
- Title: Subtitle
- Metabolomic Biomarkers of Rest-Activity Rhythms in Older Women: Results from the Women's Health Initiative (WHI) Study
- Creators
- Lingxiao Zhang - Yale UniversityChris Ho Ching Yeung - The University of Texas Health Science Center at HoustonKyoung A Viola Lee - Yale School of MedicineAladdin H Shadyab - University of California San DiegoAndrea LaCroix - Human Longevity (United States)Katie L Stone - California Pacific Medical CenterKristine Yaffe - University of California, San FranciscoKathleen M Hayden - Wake Forest UniversityRamon Casanova - Wake Forest UniversityStephen R Rapp - Wake Forest UniversityJiu-Chiuan Chen - University of Southern CaliforniaLaura Baker - Wake Forest UniversityJoAnn E Manson - Brigham and Women's HospitalYuan Huang - Yale UniversityQian Xiao - The University of Texas Health Science Center at Houston
- Resource Type
- Journal article
- Publication Details
- Sleep (New York, N.Y.), Vol.49(1), zsaf320
- DOI
- 10.1093/sleep/zsaf320
- PMID
- 41071097
- PMCID
- PMC12795739
- NLM abbreviation
- Sleep
- ISSN
- 1550-9109
- eISSN
- 1550-9109
- Publisher
- Oxford University Press
- Grant note
- American Academy of Sleep Medicine Foundation Strategic AwardNational Institute of Aging: R01AG063946, RF1AG079149, RF1AG074345 U.S. Department of Health and Human Services: 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005 National Heart, Lung, and Blood InstituteNational Institutes of Health
The work is supported by grant from the National Institute of Aging (R01AG063946 [X.Q.], and R01AG063946, RF1AG079149, and RF1AG074345 [A.H.S.]) and the American Academy of Sleep Medicine Foundation Strategic Award (X.Q.). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005.
- Language
- English
- Electronic publication date
- 10/10/2025
- Date published
- 01/13/2026
- Academic Unit
- Biostatistics
- Record Identifier
- 9985014875602771
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