Evidence map›Paper›PMID 37369886›Full record

ArticleGeroScience2024

Higher testosterone and testosterone/estradiol ratio in men are associated with decreased Pheno-/GrimAge and DNA-methylation based PAI1.

Cynthia D J Kusters, Kimberly C Paul, Ake T Lu, Luigi Ferruci, Beate R Ritz, Alexandra M Binder, Steve Horvath

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in GeroScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Observational
  5. Sex differences in DNA methylation in bats.Annals of the New York Academy of Sciences · 2025
    Article
  6. Quantification of Epigenetic Aging in Public Health.Annual review of public health · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Cynthia D J KustersDepartment of Human Genetics, David Geffen School of Medicine, Los Angeles, CA, USA. ckusters@ucla.edu.ORCID 0000-0001-8099-9026
Kimberly C PaulDepartment of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA.ORCID 0000-0002-4476-2352
Ake T LuDepartment of Human Genetics, David Geffen School of Medicine, Los Angeles, CA, USA.ORCID 0000-0002-2866-7961
Luigi FerruciLongitudinal Studies Section, Translational Gerontology Branch, National Institute On Aging, National Institutes of Health, Baltimore, USA.
Beate R RitzDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.ORCID 0000-0001-8361-3870
Alexandra M BinderDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.ORCID 0000-0003-2949-4684
Steve HorvathDepartment of Human Genetics, David Geffen School of Medicine, Los Angeles, CA, USA.ORCID 0000-0002-4110-3589
University of California, Los Angeles · USNational Institutes of Health · USUniversity of Hawaiʻi at Mānoa · US

Funding

Microbiome, Pesticides and Parkinsons in LatinosR01ES031106 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2020 to 2025
$3.8M
Oxidative stress and the pathogenesis of sarcopenia and disability in older womenR01AG027012 · NIA · JOHNS HOPKINS UNIVERSITY · PI SEMBA, RICHARD D · 2005 to 2018
$3.6M
Validation and optimization of epigenetic clocksU01AG060908 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2018 to 2022
$3.4M
The InChianti StudyZIAAG001050 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$2.1M
Immune System Aging in Parkinson’s and Alzheimer’s disease: Epigenetics, biologic aging, and heightened immune states in a population-based studyK01AG072044 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAUL, KIMBERLY · 2021 to 2025
$717k
Epigenetic Age as a Marker of Reproductive Age and Modifier of Invasive Breast Cancer Risk Among Postmenopausal WomenK07CA225856 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI BINDER, ALEXANDRA MARGARET LYNN · 2018 to 2020
$468k
Sex Hormones, Aging, Alzheimer's Disease and Other Neurodegenerative Diseases in WomenF32AG063442 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUSTERS, CYNTHIA DIANA JOHANNA · 2019 to 2021
$236k
NCI NIH HHS K07 CA225856NCI NIH HHS K07CA225856NIA NIH HHS F32 AG063442NIA NIH HHS F32AG063442NIA NIH HHS K01 AG072044NIA NIH HHS K01AG072044NIA NIH HHS N01-AG-5-0002NIA NIH HHS N01-AG-821336NIA NIH HHS N01-AG-916413NIA NIH HHS R01 AG027012NIA NIH HHS R01-AG-027012NIA NIH HHS U01 AG060908NIA NIH HHS U01AG060908NIEHS NIH HHS R01 ES031106
6 · The paper itself

Abstract

Sex hormones are hypothesized to drive sex-specific health disparities. Here, we study the association between sex steroid hormones and DNA methylation-based (DNAm) biomarkers of age and mortality risk including Pheno Age Acceleration (AA), Grim AA, and DNAm-based estimators of Plasminogen Activator Inhibitor 1 (PAI1), and leptin concentrations. We pooled data from three population-based cohorts, the Framingham Heart Study Offspring Cohort, the Baltimore Longitudinal Study of Aging, and the InCHIANTI Study, including 1,062 postmenopausal women without hormone therapy and 1,612 men of European descent. Sex-stratified analyses using a linear mixed regression were performed, with a Benjamini-Hochberg (BH) adjustment for multiple testing. Sex Hormone Binding Globulin (SHBG) was associated with a decrease in DNAm PAI1 among men (per 1 standard deviation (SD): -478 pg/mL; 95%CI: -614 to -343; P:1e-11; BH-P: 1e-10), and women (-434 pg/mL; 95%CI: -589 to -279; P:1e-7; BH-P:2e-6). The testosterone/estradiol (TE) ratio was associated with a decrease in Pheno AA (-0.41 years; 95%CI: -0.70 to -0.12; P:0.01; BH-P: 0.04), and DNAm PAI1 (-351 pg/mL; 95%CI: -486 to -217; P:4e-7; BH-P:3e-6) among men. In men, testosterone was associated with a decrease in DNAm PAI1 (-481 pg/mL; 95%CI: -613 to -349; P:2e-12; BH-P:6e-11). SHBG was associated with lower DNAm PAI1 among men and women. Higher testosterone and testosterone/estradiol ratio were associated with lower DNAm PAI and a younger epigenetic age in men. A decrease in DNAm PAI1 is associated with lower mortality and morbidity risk indicating a potential protective effect of testosterone on lifespan and conceivably cardiovascular health via DNAm PAI1.

Indexed as

DNA MethylationPlasminogen Activator Inhibitor 1DNAEstradiolFemaleGonadal Steroid HormonesHumansLongitudinal StudiesMaleTestosteroneDNAEstradiolGonadal Steroid HormonesPlasminogen Activator Inhibitor 1SERPINE1 protein, humanTestosteroneEpigenetic agePlasminogen Activator Inhibitor 1Sex differencesSex hormonesTestosterone

Identifiers

PMID37369886
PMCPMC10828310
OpenAlexW4382197199

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.