Evidence map›Paper›PMID 33383072›Full record

ArticleMechanisms of ageing and development2021

Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion.

Victor A Ansere, Samim Ali-Mondal, Roshini Sathiaseelan, Driele N Garcia, José V V Isola, Jéssica D Henseb, Tatiana D Saccon, Sarah R Ocañas, Kyla B Tooley, Michael B Stout and 2 more

Open access · greenAbstract readComparative Study
In one paragraph

Article in Mechanisms of ageing and development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

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  16. The role of IL-33/ST2 signaling in female reproductive diseases.Frontiers in cell and developmental biology · 2026
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2 more citing papers are in PubMed but not listed here.

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 at 3 institutions in 2 countries.

Victor A AnsereDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Samim Ali-MondalOklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Roshini SathiaseelanOklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Driele N GarciaDepartment of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
José V V IsolaDepartment of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Jéssica D HensebFaculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Tatiana D SacconFaculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Sarah R OcañasDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Kyla B TooleyDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Michael B StoutOklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Augusto SchneiderFaculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Willard M FreemanOklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Genes & Human Disease Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA. Electronic address: bill-freeman@omrf.org.
University of Oklahoma Health Sciences Center · USUniversidade Federal de Pelotas · BRUniversity of Oklahoma Medical Center · US

Funding

Targeted DNA Methylation and Mitochondrial Heteroplasmy CoreP30AG050911 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Veronica Galvan · 2015 to 2026
$13.9M
Sex divergence and cell specificity of age-related hippocampal DNA modificationsR01AG059430 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FREEMAN, WILLARD M · 2019 to 2023
$2.7M
Cellular senescence and epigenomic remodeling in ovarian agingR01AG069742 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI STOUT, MICHAEL B · 2020 to 2024
$2.0M
Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiolR00AG051661 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI STOUT, MICHAEL B · 2018 to 2020
$746k
Sex divergence and cell specificity of age-related hippocampal DNA modificationsR56AG059430 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FREEMAN, WILLARD M · 2018 to 2018
$558k
Epigenetic regulation of sexually divergent neuroinflammation with brain aging and Alzheimer's diseaseF31AG064861 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI OCANAS, SARAH RENEE · 2019 to 2021
$94k
Dynamics of the brain epigenome with agingI01BX003906 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI FREEMAN, WILLARD M · 2018 to 2021
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BLRD VA I01 BX003906NIA NIH HHS F31 AG064861NIA NIH HHS P30 AG050911NIA NIH HHS R00 AG051661NIA NIH HHS R01 AG059430NIA NIH HHS R01 AG069742NIA NIH HHS R56 AG059430
6 · The paper itself

Abstract

Decline in ovarian reserve with advancing age is associated with reduced fertility and the emergence of metabolic disturbances, osteoporosis, and neurodegeneration. Recent studies have provided insight into connections between ovarian insufficiency and systemic aging, although the basic mechanisms that promote ovarian reserve depletion remain unknown. Here, we sought to determine if chronological age is linked to changes in ovarian cellular senescence, transcriptomic, and epigenetic mechanisms in a mouse model. Histological assessments and transcriptional analyses revealed the accumulation of lipofuscin aggresomes and senescence-related transcripts (Cdkn1a, Cdkn2a, Pai-1 and Hmgb1) significantly increased with advancing age. Transcriptomic profiling and pathway analyses following RNA sequencing, revealed an upregulation of genes related to pro-inflammatory stress and cell-cycle inhibition, whereas genes involved in cell-cycle progression were downregulated; which could be indicative of senescent cell accumulation. The emergence of these senescence-related markers preceded the dramatic decline in primordial follicle reserve observed. Whole Genome Oxidative Bisulfite Sequencing (WGoxBS) found no genome-wide or genomic context-specific DNA methylation and hydroxymethylation changes with advancing age. These findings suggest that cellular senescence may contribute to ovarian aging, and thus, declines in ovarian follicular reserve. Cell-type-specific analyses across the reproductive lifespan are needed to fully elucidate the mechanisms that promote ovarian insufficiency.

Indexed as

Cellular SenescenceOvarian ReserveAge FactorsAgingAnimalsCell Cycle ProteinsCytokinesDNA MethylationEpigenesis, GeneticFemaleGene Expression ProfilingInflammation MediatorsMiceMice, Inbred C57BLOvarian FollicleOvaryCell Cycle ProteinsCytokinesInflammation MediatorsAgingCellular senescenceDNA methylationEpigeneticsOvary

Identifiers

PMID33383072
PMCPMC8279026
OpenAlexW3117460981

What Socratic holds

Textmetadata
LicenceTDM
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.