Evidence map›Paper›PMID 39956852›Full record

ArticleNature communications2025

A multiparametric anti-aging CRISPR screen uncovers a role for BAF in protein synthesis regulation.

Sophia Y Breusegem, Jack Houghton, Raquel Romero-Bueno, Adrián Fragoso-Luna, Katherine A Kentistou, Ken K Ong, Anne F J Janssen, Nicholas A Bright, Christian G Riedel, John R B Perry and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Sophia Y BreusegemCambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Keith Peters Building, Hills Road, Cambridge, UK.
Jack HoughtonCambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Keith Peters Building, Hills Road, Cambridge, UK.
Raquel Romero-Bueno *Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas-Universidad Pablo de Olavide-Junta de Andalucía, Seville, Spain.
Adrián Fragoso-Luna *Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas-Universidad Pablo de Olavide-Junta de Andalucía, Seville, Spain.ORCID http://orcid.org/0000-0003-0325-7293
Katherine A KentistouMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.ORCID http://orcid.org/0000-0002-5816-664X
Ken K OngMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.ORCID http://orcid.org/0000-0003-4689-7530
Anne F J JanssenCambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Keith Peters Building, Hills Road, Cambridge, UK.
Nicholas A BrightCambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Keith Peters Building, Hills Road, Cambridge, UK.ORCID http://orcid.org/0000-0002-2791-6727
Christian G RiedelKarolinska Institutet, Blickagången 16, 141 57, Huddinge, Sweden.ORCID http://orcid.org/0000-0002-3689-8022
John R B PerryMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.ORCID http://orcid.org/0000-0001-6483-3771
Peter AskjaerCentro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas-Universidad Pablo de Olavide-Junta de Andalucía, Seville, Spain.ORCID http://orcid.org/0000-0003-3192-4428
Delphine LarrieuCambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Keith Peters Building, Hills Road, Cambridge, UK. dlarrieu@altoslabs.com.ORCID http://orcid.org/0000-0002-2335-9361

Funding

Cancerfonden (Swedish Cancer Society) 20 1034 PjFederation of European Biochemical Societies (FEBS) N/ARCUK | Medical Research Council (MRC) MC_UU_00006/2RCUK | Medical Research Council (MRC) MC_UU_12015/2RCUK | Medical Research Council (MRC) MR/M010007/1RCUK | Medical Research Council (MRC) MR/R0009015/1Vetenskapsrådet (Swedish Research Council) 2017-06088Vetenskapsrådet (Swedish Research Council) 2019-04868Wellcome TrustWellcome Trust (Wellcome) 204845/Z/16/ZWellcome Trust (Wellcome) 206242/Z/17/Z
6 · The paper itself

Abstract

Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Here, we report a whole genome, multiparametric CRISPR screen, identifying 43 genes that can rescue multiple cellular phenotypes associated with progeria. We implement the screen in fibroblasts from Néstor-Guillermo Progeria Syndrome male patients, carrying a homozygous A12T mutation in BAF. The hits are enriched for genes involved in protein synthesis, protein and RNA transport and osteoclast formation and are validated in a whole-organism Caenorhabditis elegans model. We further confirm that BAF A12T can disrupt protein synthesis rate and fidelity, which could contribute to premature aging in patients. This work highlights the power of multiparametric genome-wide suppressor screens to identify genes enhancing cellular resilience in premature aging and provide insights into the biology underlying progeria-associated cellular dysfunction.

Indexed as

AgingDNA-Binding ProteinsNuclear ProteinsProgeriaProtein BiosynthesisAnimalsCaenorhabditis elegansClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsFibroblastsHumansMaleMutationDNA-Binding ProteinsNuclear Proteins

Identifiers

PMID39956852
PMCPMC11830792

What OpenQuestion holds

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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.