Evidence map›Paper›PMID 41270125›Full record

ArticlePLoS biology2025

The efficacy of longevity interventions in Caenorhabditis elegans is determined by the early life activity of RNA splicing factors.

Sneha Dutta, Maria Camila Perez Matos, Caroline Heintz, Ayse Sena Mutlu, Mary Piper, Meeta Mistry, Arpit Sharma, Christopher S Morrow, Hannah Smith, Porsha Howell and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

14 authors.

Sneha DuttaDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Maria Camila Perez MatosDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Caroline HeintzDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Ayse Sena MutluHuffington Center on Aging, Baylor College of Medicine, Houston, Texas, United States of America.
Mary PiperHarvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Meeta MistryHarvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Arpit SharmaDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Christopher S MorrowDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Hannah SmithDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Porsha HowellDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Rohan SehgalDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Anne LanjuinDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Meng C WangHuffington Center on Aging, Baylor College of Medicine, Houston, Texas, United States of America.
William B MairDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.ORCID 0000-0002-0661-1342

Funding

Mechanisms Specific to the Beneficial Effects of Dietary RestrictionR01AG044346 · NIA · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI William B Mair · 2013 to 2026
$3.8M
Targeting RNA homeostasis to promote healthy agingR01AG051954 · NIA · HARVARD SCHOOL OF PUBLIC HEALTH · PI MAIR, WILLIAM B · 2017 to 2020
$1.7M
Harnessing Redox Regulation of Proteasome Function to Promote Healthy AgingF32AG085703 · NIA · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Christopher Scott Morrow · 2024 to 2026
$250k
NIA NIH HHS F32 AG085703NIA NIH HHS R01 AG044346NIA NIH HHS R01 AG051954
6 · The paper itself

Abstract

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between predicted life span and alternative splicing of mRNAs related to lipid metabolism. The activity of two RNA splicing factors, Reversed Polarity-1 (REPO-1) and Splicing Factor 1 (SFA-1), early in life is necessary for C. elegans response to specific longevity interventions and leads to context-specific changes to fat content that is mirrored by knockdown of their direct target POD-2/ACC1. Moreover, POD-2/ACC1 is required for the same longevity interventions as REPO-1/SFA-1. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together, we propose that splicing factor activity establishes a cellular landscape early in life that enables responsiveness to specific longevity interventions and may explain variance in efficacy between individuals.

Indexed as

Caenorhabditis elegansCaenorhabditis elegans ProteinsLongevityRNA Splicing FactorsAgingAlternative SplicingAnimalsLipid MetabolismCaenorhabditis elegans ProteinsRNA Splicing Factors

Identifiers

PMID41270125
PMCPMC12671814

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.