Journal article
Metabolomic Biomarkers of Rest-Activity Rhythms in Older Men: results from the Osteoporotic Fractures in Men study (MrOS) Study
Sleep (New York, N.Y.), Vol.49(1), zsaf319
01/13/2026
DOI: 10.1093/sleep/zsaf319
PMCID: PMC12795748
PMID: 41071109
Abstract
Rest-activity rhythm characteristics have been linked to a wide range of health conditions; however, the molecular mechanisms underlying these associations are not well understood. This study is the first of two studies aimed at using an untargeted approach to identify metabolomic markers associated with rest-activity rhythm characteristics and focuses on older men.
The study included 950 participants from the Osteoporotic Fractures in Men study. Multiple parametric and non-parametric variables of rest-activity rhythms were derived from actigraphy data. A total of 848 metabolites were measured from fasting blood samples using an untargeted approach. Multiple linear regression models and Ingenuity Pathway Analysis (IPA) were used to identify metabolomic profiles associated with rest-activity variables.
We found 65 metabolites, mostly amino acids and lipids, that were significantly associated with at least one of the primary rest-activity variables (i.e., pseudo F-statistic, intradaily variability and interdaily stability). These metabolites were from various biochemical pathways, including diacylglycerol, plasmalogen, lysoplasmalogen, and amino sugar metabolism. The IPA suggested that these metabolites may be implicated in various diseases and functions, particularly immune and inflammatory diseases, and identified the PEX2-PEX5 network as a significantly enriched gene-regulation pathway.
Our findings expand the current knowledge about the relationship between diurnal behaviors and human metabolism, and provide new evidence regarding mechanistic pathways that may mediate the adverse health effects of impaired rest-activity rhythms in older men.
Details
- Title: Subtitle
- Metabolomic Biomarkers of Rest-Activity Rhythms in Older Men: results from the Osteoporotic Fractures in Men study (MrOS) Study
- Creators
- Lingxiao Zhang - Yale UniversityKyoung A Viola Lee - Yale School of MedicineKatie Stone - California Pacific Medical CenterAndrea LaCroix - Human Longevity (United States)Aladdin H Shadyab - University of California San DiegoKristine Yaffe - University of California, San FranciscoSusan Redline - Brigham and Women's HospitalDeborah Kado - Geriatric Research Education and Clinical CenterChris Ho Ching Yeung - The University of Texas Health Science Center at HoustonShuaichao Wang - Pittsburg State UniversityYuan 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), zsaf319
- DOI
- 10.1093/sleep/zsaf319
- PMID
- 41071109
- PMCID
- PMC12795748
- 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 Arthritis and Musculoskeletal and Skin Diseases: U01 AR066160 National Center for Advancing Translational Sciences: UL1 TR002369 NIH Roadmap for Medical ResearchNational Heart, Lung, and Blood Institute: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839 National Institutes of HealthNational Institute on Aging: R01 AG063946, RF1 AG079149, RF1 AG074345, U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, R01 AG066671
The work is supported by grants from the National Institute on Aging (NIA) (R01 AG063946 (X.Q.) and R01 AG063946, RF1 AG079149, and RF1 AG074345 (A.H.S.)) and the American Academy of Sleep Medicine Foundation Strategic Award (X.Q.). The MrOS study is supported by National Institutes of Health funding. The following institutes provide support: the NIA under grant numbers U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, R01 AG066671, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under grant number U01 AR066160, the National Center for Advancing Translational Sciences (NCATS) under grant number UL1 TR002369, and NIH Roadmap for Medical Research. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.
- Language
- English
- Electronic publication date
- 10/10/2025
- Date published
- 01/13/2026
- Academic Unit
- Biostatistics
- Record Identifier
- 9985014871202771
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