Evidence map›Paper›PMID 40601216›Full record

ArticleGeroScience2026

End-of-life pathology in UM-HET3 mice treated with 16 α‑hydroxyestradiol or late‑start canagliflozin.

Jessica M Snyder, David E Harrison, Ron Korstanje, Brett Ginsburg, Peter C Reifsnyder, James Nelson, Scott Leiser, Catherine Kaczorowski, Denise M Imai, Adam B Salmon and 3 more

Abstract read
In one paragraph

Article in GeroScience, 2026. 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

13 authors.

Jessica M SnyderDepartment of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA. snyderjm@uw.edu.ORCID 0000-0002-0470-0931
David E HarrisonThe Jackson Laboratory, Bar Harbor, ME, USA.
Ron KorstanjeThe Jackson Laboratory, Bar Harbor, ME, USA.
Brett GinsburgBarshop Institute for Longevity and Aging Studies and Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Peter C ReifsnyderThe Jackson Laboratory, Bar Harbor, ME, USA.
James NelsonBarshop Institute for Longevity and Aging Studies and Departments of Molecular Medicine and Cellular and Integrative Physiology, The University of Texas Health Science Center, San Antonio, TX, USA.
Scott LeiserDepartment of Molecular & Integrative Physiology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA.
Catherine KaczorowskiDepartment of Neurology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA.
Denise M ImaiDepartment of Pathology, Microbiology and Immunology, University of California, Davis, CA, USA.
Adam B SalmonBarshop Institute for Longevity and Aging Studies and Departments of Molecular Medicine and Cellular and Integrative Physiology, The University of Texas Health Science Center, San Antonio, TX, USA.
Randy StrongBarshop Institute for Longevity and Aging Studies and Department of Pharmacology, The University of Texas Health Science Center, San Antonio, TX, USA.
Warren LadigesDepartment of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Richard A MillerDepartment of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA.

Funding

Interventions That Retard Mammalian AgingU01AG022308 · NIA · JACKSON LABORATORY · PI Ronny Korstanje · 2003 to 2026
$30.5M
Research Education CoreP30AG024824 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Lona Mody, RAYMOND L YUNG · 2004 to 2026
$29.2M
Center for Testing Potential Anti-Aging InterventionsU01AG022307 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI RANDY STRONG, Adam Salmon · 2004 to 2026
$26.3M
Laboratory for Anti-Geric Testing, Evaluation and ResearchU01AG022303 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RICHARD A MILLER · 2003 to 2026
$25.4M
NIA NIH HHS AG022303NIA NIH HHS AG022307NIA NIH HHS AG022308NIA NIH HHS P30 AG024824NIA NIH HHS U01 AG022303NIA NIH HHS U01 AG022307NIA NIH HHS U01 AG022308
6 · The paper itself

Abstract

Canagliflozin (Cana) started  at 16 months of age and 16-hydroxy-estradiol (OH_Est) started at 12 months each led to significant increases in lifespan in male UM-HET3 mice but significant decreases in female lifespan. To seek insights into the basis for these sex-specific effects, we performed end-of-life histopathological analyses of control and treated mice for all three interventions testing program sites. There were no significant drug-induced alterations in inferred cause of death, although statistical power was low for such comparisons. Tabulation of incidental lesions (i.e., combining lethal and non-lethal lesions) revealed a complex set of significant and near-significant changes caused by each of the two agents, in some cases absent, or even opposite in direction, in one of the two sexes. The analysis did not, however, reveal a clear pattern that would explain the selective sex-specific effects of either agent on lifespan. It is plausible that the female-specific harm induced by each of these agents could reflect harmful or toxic effects that are not easily detectable by histopathological examination.

Indexed as

CanagliflozinEstradiolLongevityAnimalsFemaleMaleMiceSex FactorsCanagliflozinEstradiolCanagliflozinCause of deathPathology

Identifiers

PMID40601216
PMCPMC12972294

What OpenQuestion holds

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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 OpenQuestion graph.