Evidence map›Paper›PMID 41512022›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation.

Janine Sengstack, Jiashun Zheng, Turan Aghayev, Gregor Bieri, Michael Mobaraki, Jue Lin, Changhui Deng, Saul A Villeda, Hao Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. 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. Review
  3. Review
  4. Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    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

9 authors.

Janine Sengstack *Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.ORCID 0000-0002-2167-494X
Jiashun Zheng *Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.ORCID 0000-0003-3266-4461
Turan Aghayev *Department of Anatomy, University of California, San Francisco, CA 94143.
Gregor BieriDepartment of Anatomy, University of California, San Francisco, CA 94143.ORCID 0000-0003-0737-231X
Michael MobarakiDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.ORCID 0000-0002-6080-7258
Jue LinDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.
Changhui DengDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.
Saul A VilledaDepartment of Anatomy, University of California, San Francisco, CA 94143.
Hao LiDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.

Funding

PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
Cellular Aging and Rejuvenation: A Comprehensive Picture from a Dynamic and Network Perspective - Administrative SupplementR01AG058742 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KENNEDY, BRIAN K, LI, HAO · 2018 to 2022
$3.0M
Cellular and Tissue Rejuvenation through Transcriptional ReprogrammingR01AG083524 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAO LI, SAUL A VILLEDA · 2023 to 2026
$2.5M
American Federation for Aging Research (AFAR) N/AC&Z Biohub San Francisco Investigator N/AHHS | NIH | National Institute on Aging (NIA) R01AG058742HHS | NIH | National Institute on Aging (NIA) R01AG083524NIA NIH HHS R01 AG058742NIA NIH HHS R01 AG083524NICHD NIH HHS T32 HD007470
6 · The paper itself

Abstract

Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq screening, we developed a systematic approach to identify single transcription factor (TF) perturbations that promote rejuvenation without dedifferentiation. Overexpressing E2F3 or EZH2, and repressing STAT3 or ZFX, reversed cellular hallmarks of aging-increasing proliferation, proteostasis, and mitochondrial activity, while decreasing senescence. EZH2 overexpression in vivo rejuvenated livers in aged mice, reversing aging-associated gene expression profiles, decreasing steatosis and fibrosis, and improving glucose tolerance. Mechanistically, single TF perturbations led to convergent downstream transcriptional programs conserved in different aging and rejuvenation models. These results suggest a shared set of molecular requirements for cellular and tissue rejuvenation across species.

Indexed as

RejuvenationTranscription FactorsAgingAnimalsCell ProliferationCellular SenescenceFibroblastsHumansLiverMiceTranscription Factorsliver agingPerturb-seq screeningrejuvenationreplicative aging

Identifiers

PMID41512022
PMCPMC12799168

What OpenQuestion holds

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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.