Evidence mapPaperPMID 39672978Full record

ArticleGeroScience2025

Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice.

José V V Isola, Subhasri Biswas, Hashan Jayarathne, Chase R Hubbart, Jessica D Hense, Satoshi Matsuzaki, Michael T Kinter, Kenneth M Humphries, Sarah R Ocañas, Marianna Sadagurski and 1 more

Abstract read
In one paragraph

Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Multi-contrast optical coherence tomography forBiomedical optics express · 2026
    Article
  3. Review
  4. 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

11 authors.

José V V IsolaAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Subhasri BiswasAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Hashan JayarathneDepartment of Biological Sciences, Institute of Environmental Health Sciences, Integrative Biosciences Center, Wayne State University, Detroit, MI, 48202, USA.
Chase R HubbartAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Jessica D HenseAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Satoshi MatsuzakiAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Michael T KinterAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Kenneth M HumphriesAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA.
Sarah R OcañasGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Marianna SadagurskiDepartment of Biological Sciences, Institute of Environmental Health Sciences, Integrative Biosciences Center, Wayne State University, Detroit, MI, 48202, USA.
Michael B StoutAging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13 Street, Chapman E306, Oklahoma City, OK, 73104, USA. michael-stout@omrf.org.ORCID 0000-0002-9996-9123

Funding

Viral sensor IFIH1 promotes SLE through an altered interferon programP20GM139763 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2022 to 2025
$12.5M
Pilot and Feasibility ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$4.9M
Proteomics CoreP20GM103447 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$4.2M
IDeA National Resource for Quantitative ProteomicsR24GM137786 · UNIV OF ARKANSAS FOR MED SCIS · 2025 to 2025
$2.1M
Research Development CoreP30AG050911 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$1.3M
Canagliflozin as a Neuroprotective Agent to Improve Neuroinflammation and Cognitive Function during AgingRF1AG078170 · NIA · WAYNE STATE UNIVERSITY · PI Marianna Sadagurski · 2023 to 2023
$1.2M
Benzene exposure promotes neuroinflammation and metabolic dysregulationR01ES033171 · NIEHS · WAYNE STATE UNIVERSITY · 2024 to 2025
$739k
Global Consortium for Reproductive Longevity and Equality GCRLE-0523Global Consortium for Reproductive Longevity and Equality GCRLE-4501NIA NIH HHS AG069742NIA NIH HHS P30 AG050911NIA NIH HHS R01 AG069742NIA NIH HHS RF1 AG078170NIDDK NIH HHS P30 DK020572NIEHS NIH HHS R01 ES033171NIEHS NIH HHS R56 ES034765NIGMS NIH HHS P20 GM103447NIGMS NIH HHS P20 GM139763NIGMS NIH HHS R24 GM137786
6 · The paper itself

Abstract

Ovarian aging is characterized by declines in follicular reserve and the emergence of mitochondrial dysfunction, reactive oxygen species production, inflammation, and fibrosis, which eventually results in menopause. Menopause is associated with increased systemic aging and the development of numerous comorbidities; therefore, the attenuation of ovarian aging could also delay systemic aging processes in women. Recent work has established that the anti-diabetic drug Canagliflozin (Cana), a sodium-glucose transporter 2 inhibitor, elicits benefits on aging-related outcomes, likely through the modulation of nutrient-sensing pathways and metabolic homeostasis. Given that nutrient-sensing pathways play a critical role in controlling primordial follicle activation, we sought to determine if chronic Cana administration would delay ovarian aging and curtail the emergence of pathological hallmarks associated with reproductive senescence. We found that mice receiving Cana maintained their ovarian reserve through 12 months of age, which was associated with declines in primordial follicles FoxO3a phosphorylation, a marker of activation, when compared to the age-matched controls. Furthermore, Cana treatment led to decreased collagen, lipofuscin, and T cell accumulation at 12 months of age. Whole ovary transcriptomic and proteomic analyses revealed subtle improvements, predominantly in mitochondrial function and the regulation of cellular proliferation. Pathway analyses of the transcriptomic data revealed a downregulation in cell proliferation and mitochondrial dysfunction signatures, with an upregulation of oxidative phosphorylation. Pathway analyses of the proteomic data revealed declines in signatures associated with PI3K/AKT activity and lymphocyte accumulation. Collectively, we demonstrate that Cana treatment can delay ovarian aging in mice and could potentially have efficacy for delaying ovarian aging in women.

Indexed as

AgingCanagliflozinOvarian FollicleOvarian ReserveOvarySodium-Glucose Transporter 2 InhibitorsAnimalsFemaleForkhead Box Protein O3MiceMice, Inbred C57BLCanagliflozinForkhead Box Protein O3Sodium-Glucose Transporter 2 InhibitorsFertilityFibrosisGlucoseInsulinOvarySGLT2

Identifiers

PMID39672978
PMCPMC12181533

What Socratic holds

Textmetadata
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.