Evidence map›Paper›PMID 39680477›Full record

ArticleAging cell2025

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny.

Amy R Vandiver, Alejandro Torres, Amberly Sanden, Thang L Nguyen, Jasmine Gasilla, Mary T Doan, Vahan Martirosian, Austin Hoang, Jonathan Wanagat, Michael A Teitell

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 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. Review
  2. Article
  3. Article
  4. Novel advanced patient-derivedFrontiers in neurology
    Review
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

10 authors.

Amy R VandiverDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.ORCID 0000-0003-2176-9161
Alejandro TorresDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Amberly SandenDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Thang L NguyenDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Jasmine GasillaDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Mary T DoanDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.ORCID 0000-0001-6295-4895
Vahan MartirosianDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Austin HoangDivision of Geriatrics, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Jonathan WanagatVeterans Administration Greater Los Angeles Healthcare System, Los Angeles, California, USA.ORCID 0000-0002-8460-8616
Michael A TeitellDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
UCLA-CDU CFARP30AI152501 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Kara W Chew · 2022 to 2026
$15.6M
Multiphoton Microscope for Deep Tissue ImagingS10OD025017 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENTOLILA, LAURENT A. · 2018 to 2018
$599k
Understanding mitochondrial mutations that drive human tissue agingK08AG086582 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Amy R. Vandiver · 2024 to 2026
$521k
California Institute for Regenerative Medicine EDUC2-08411CSUNDermatology FoundationMelanoma Research AllianceNCI NIH HHS P30 CA016042NIAID NIH HHS P30 AI152501NIA NIH HHS K08 AG086582NIH award 1K08AG086582-01NIH award P30CA016042NIH HHS S10 OD025017Rose Hills Foundation
6 · The paper itself

Abstract

The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated in aging and disease, although the impact of this shift on cell function is challenging to assess. Reprogramming to pluripotency affects mtDNA mutation heteroplasmy. We reprogrammed three human fibroblast lines with known heteroplasmy for deleterious mtDNA point or deletion mutations. Quantification of mutation heteroplasmy in the resulting 76 induced pluripotent stem cell (iPSC) clones yielded a bimodal distribution, creating three sets of clones with high levels or absent mutation heteroplasmy with matched nuclear genomes. iPSC clones with elevated deletion mutation heteroplasmy show altered growth dynamics, which persist in iPSC-derived progenitor cells. We identify transcriptomic and metabolic shifts consistent with increased investment in neutral lipid synthesis as well as increased epigenetic age in high mtDNA deletion mutation iPSC, consistent with changes occurring in cellular aging. Together, these data demonstrate that high mtDNA mutation heteroplasmy induces changes occurring in cellular aging.

Indexed as

Cell DifferentiationCellular SenescenceDNA, MitochondrialHeteroplasmyInduced Pluripotent Stem CellsMitochondriaMutationPluripotent Stem CellsFibroblastsHumansPhenotypeDNA, MitochondrialagingiPSCmitochondriamtDNA mutation

Identifiers

PMID39680477
PMCPMC11896400

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.