Evidence map›Paper›PMID 41282809›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Ticking Differently: Elucidating Sexual Dimorphism in Human Aging through Metabolomics, Proteomics and Genomics.

Sihao Xiao, Pallavi Kaushik, Gaoyu Du, Bowen Liu, Salman B Hosawi, Benoit Hastoy, M Austin Argentieri, Laura M Winchester, Alejo J Nevado-Holgado, Rima Kaddurah-Daouk and 2 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Sihao XiaoNuffield Department of Population Health, University of Oxford, Oxford, UK.
Pallavi KaushikNuffield Department of Population Health, University of Oxford, Oxford, UK.
Gaoyu DuOxford Internet Institute, Oxford University, Oxford, UK.
Bowen LiuNuffield Department of Population Health, University of Oxford, Oxford, UK.
Salman B HosawiCentre of Artificial Intelligence in Precision Medicine (CAIPM), King Abdulaziz University, Jeddah, Saudi Arabia.
Benoit HastoyCentre of Artificial Intelligence in Precision Medicine (CAIPM), King Abdulaziz University, Jeddah, Saudi Arabia.
M Austin ArgentieriAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Laura M WinchesterDepartment of Psychiatry, University of Oxford, Oxford, UK.
Alejo J Nevado-HolgadoCentre of Artificial Intelligence in Precision Medicine (CAIPM), King Abdulaziz University, Jeddah, Saudi Arabia.
Rima Kaddurah-DaoukDepartment of Medicine, Duke University, Durham, NC, USA.
Najaf AminNuffield Department of Population Health, University of Oxford, Oxford, UK.
Cornelia van DuijnNuffield Department of Population Health, University of Oxford, Oxford, UK.

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Project 4 - Mechanistic studies on the role of the gut microbiome in models for Alzheimer's diseaseU19AG063744 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Rima F Kaddurah-Daouk · 2019 to 2026
$54.1M
Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0M
NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG061359NIA NIH HHS U19 AG063744Wellcome Trust
6 · The paper itself

Abstract

That males and females age differently has been overlooked while developing aging clocks. Here, we developed a sex-specific metabolic aging clock in 390,941 individuals from the UK Biobank and integrated it with genetic, proteomic and epidemiological data to identify mechanisms accelerating/decelerating metabolic aging in males and females. Our findings reveal dysregulation of cholesterol metabolism, immune system, hemostasis, and cell growth, survival and apoptosis as common mechanisms accelerating metabolic aging in males and females, and upregulation of oxidative stress detoxification, cellular resilience and tissue integrity as common mechanisms decelerating metabolic aging. In females, a further dysregulation of carbohydrate/glucose metabolism, circadian rhythm and hormone metabolism accelerating metabolic aging is observed, while dysregulation of energy metabolism, cancer and longevity pathway is specifically observed in males. Among reproductive factors, late puberty and higher parity manifest as protective factors, decelerating metabolic aging in both sexes, and additionally childbirth at older age decelerating metabolic aging in women. Accelerated metabolic age strongly predicted morbidity and mortality in both sexes, except that the magnitude of association was several folds higher in males, and obesity explained most of the disease associations in females, suggesting that obesity influences metabolic aging and subsequent health outcomes differently in males and females. Consistent with the upregulation of molecular mechanisms involved in cancer in males, accelerated metabolic aging predicted several common cancers in males but not females. Our study provides novel insights into the biological mechanisms underlying aging and disease susceptibility in males and females, underscoring the importance of considering sex differences in healthcare strategies and public health policies.

Identifiers

PMID41282809
PMCPMC12636674

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.