Evidence map›Paper›PMID 41071109›Full record

Observational studySleep2026

Metabolomic biomarkers of rest-activity rhythms in older men: results from the Osteoporotic Fractures in Men (MrOS) study.

Lingxiao Zhang, Kyoung A Viola Lee, Katie Stone, Andrea LaCroix, Aladdin H Shadyab, Kristine Yaffe, Susan Redline, Deborah Kado, Chris Ho Ching Yeung, Shuaichao Wang and 2 more

Abstract readObservational Study
In one paragraph

Observational study in Sleep, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Fluctuations in Sleep Duration and Timing and Cardiometabolic Risk.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Lingxiao ZhangDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, United States.
Kyoung A Viola LeeDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, United States.
Katie StoneCalifornia Pacific Medical Center Research Institute, San Francisco, CA, United States.
Andrea LaCroixHerbert 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, United States.ORCID 0000-0002-9532-976X
Aladdin H ShadyabHerbert 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, United States.
Kristine YaffeDepartments of Psychiatry, Neurology and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States.
Susan RedlineBrigham and Women's Hospital, Harvard Medical School, Harvard T.H. Chan School of Public Health, Boston, MA, United States.ORCID 0000-0002-6585-1610
Deborah KadoGeriatric Research, Education, and Clinical Center (GRECC), Veterans Health Administration, Stanford University, Palo Alto, CA, United States.ORCID 0000-0002-2582-5573
Chris Ho Ching YeungDepartment of Epidemiology, University of Texas Health Sciences Center at Houston School of Public Health, Houston, TX, United States.ORCID 0000-0003-2753-1728
Shuaichao WangUPMC Hillman Cancer Center, University of Pittsburg, Pittsburg, PA, United States.
Yuan HuangDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, United States.ORCID 0000-0002-8011-3034
Qian XiaoDepartment of Epidemiology, University of Texas Health Sciences Center at Houston School of Public Health, Houston, TX, United States.ORCID 0000-0002-8388-1178

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Long term fracture risk and change in peripheral bone in the oldest old men: The MrOS studyR01AG066671 · NIA · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI BOUXSEIN, MARY L, CAWTHON, PEGGY MANNEN · 2020 to 2024
$13.3M
Outcomes of Sleep Disorders in Older MenR01HL071194 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI STONE, KATIE L · 2003 to 2013
$12.2M
Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3M
Plasma Proteomic Signatures for Alzheimer's Disease and Related DementiasRF1AG079149 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MCEVOY, LINDA KATHLEEN, SHADYAB, ALADDIN · 2022 to 2022
$7.5M
Osteoporotic Fractures in Men (MrOS) - MinneapolisU01AG042145 · NIA · UNIVERSITY OF MINNESOTA · PI ENSRUD, KRISTINE · 2013 to 2019
$5.3M
Osteporotic Fractures in Men (MrOS)- Admin CenterU01AG027810 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2017
$5.1M
Twenty-four hour patterns of light and activity and Alzheimer's Disease and Related Dementia: interplay with multi-omics biomarkers and AD pathogenesis pathwaysR01AG063946 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Qian Xiao · 2020 to 2026
$3.3M
Osteoporotic Fractures in Men (MrOS) - PortlandU01AG042124 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2013 to 2019
$3.0M
Osteoporatic Fractures in Men (MrOS)U01AG042168 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KADO, DEBORAH · 2013 to 2017
$3.0M
Osteoporotic Fractures in Men (Mr. Os) Palo AltoU01AG042143 · NIA · STANFORD UNIVERSITY · PI STEFANICK, MARCIA L. · 2013 to 2017
$3.0M
Osteoporotic Fractures in Men (Mr.OS)U01AG042139 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CAULEY, JANE ANN · 2013 to 2017
$2.9M
American Academy of Sleep Medicine Foundation Strategic AwardNCATS NIH HHS UL1 TR002369NHLBI NIH HHS R01 HL070837NHLBI NIH HHS R01 HL070838NHLBI NIH HHS R01 HL070839NHLBI NIH HHS R01 HL070841NHLBI NIH HHS R01 HL070842NHLBI NIH HHS R01 HL070847NHLBI NIH HHS R01 HL070848NHLBI NIH HHS R01 HL071194NIAMS NIH HHS U01 AR066160NIA NIH HHS R01 AG063946NIA NIH HHS R01 AG066671NIA NIH HHS RF1 AG074345NIA NIH HHS RF1 AG079149NIA NIH HHS U01 AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01 AG042143NIA NIH HHS U01 AG042145NIA NIH HHS U01 AG042168NIH HHSNIH Roadmap for Medical Research
6 · The paper itself

Abstract

STUDY

objectivesRest-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 aiming to use an untargeted approach to identify metabolomic markers associated with rest-activity rhythm characteristics and focuses on older men.

methodsThe 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.

resultsWe 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.

conclusionsOur 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. Statement of Significance In this metabolomics study in older men, we found a large number of metabolites that were associated with rest-activity rhythms. Our findings expand the current knowledge about the relationship between circadian-regulated diurnal behaviors and human metabolism, reinforce the critical role of circadian function in health and diseases, and provide new evidence regarding mechanistic pathways that may mediate the adverse effects of circadian disruptions. Our findings also point to ample future directions for further research to further elucidate the relationships among rest-activity rhythms, metabolomic profiles, and disease risk, which may help identifying intermediate targets for developing disease therapies and developing models for disease risk prediction and management.

Indexed as

ExerciseMetabolomeMetabolomicsOsteoporotic FracturesRestActigraphyAgedAged, 80 and overBiomarkersHumansLinear ModelsMalePeriodicitySignal TransductionBiomarkersacitgraphyagingbiomarkerscircadian rhythmsepidemiologymetabolomicsolder adults

Identifiers

PMID41071109
PMCPMC12795748

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.