Evidence map›Paper›PMID 42258352›Full record

ArticleCell reports2026

Hormetic fasting extends Caenorhabditis elegans lifespan via H3K27 acetylation of lipid catabolism and antioxidant genes.

Yifei Zhou, Fasih M Ahsan, Sainan Li, Mengjiao Song, Jen F Rotti, Armen Yerevanian, Yidong Shen, Alexander A Soukas

Abstract read

In one paragraph

Article in Cell reports, 2026. 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.

A simplified intermittent fasting regimen robustly extendsbioRxiv : the preprint server for biology · 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

8 authors.

Yifei ZhouDepartment of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: zhouyifei@cpu.edu.cn.

Fasih M AhsanCenter for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Biological and Biomedical Sciences, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.

Sainan LiCenter for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Mengjiao SongState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

Jen F RottiCenter for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Armen YerevanianCenter for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Yidong ShenState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

Alexander A SoukasCenter for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: asoukas@mgh.harvard.edu.

Funding

ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026

$31.6M

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026

$7.5M

P&F programP30DK135043 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Deborah J Wexler · 2023 to 2026

$5.4M

Genetic mechanisms of metformin's pro-longevity and anti-cancer effectsR01AG058256 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI SOUKAS, ALEXANDER A · 2018 to 2022

$3.0M

Mitochondrial action of metformin in aging and longevityR01AG069677 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI SOUKAS, ALEXANDER A · 2020 to 2024

$2.1M

NIA NIH HHS R01 AG058256NIA NIH HHS R01 AG069677NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK135043NIH HHS P40 OD010440

6 · The paper itself

Abstract

Exposure to low levels of environmental challenges, known as hormetic stress, fosters subsequent stress resistance and promotes healthy aging in later life. However, specific mechanisms governing transcriptional reprogramming upon hormetic nutrient stress remain elusive. Here, we identify histone H3 lysine 27 acetylation (H3K27ac) as a crucial driver of transcriptomic adaptation to hormetic fasting. Beyond its immediate function of enhancing lipid catabolism for alternative energy sources, stress-induced H3K27ac activates lifelong antioxidant defenses, thereby reducing reactive oxygen species (ROS) produced by stress-induced fatty acid oxidation and their accumulation during aging. Induced H3K27ac at metabolic genes, mediated by the pioneer factor PHA-4/FOXA, the cooperating transcription factor NHR-49/HNF4, and the nucleoporin 50 (NPP-16/NUP50), is crucial for lifespan extension under hormetic nutrient stress in Caenorhabditis elegans. Our findings establish H3K27ac as a key transcriptional switch bridging nutrient status with transcriptomic reprogramming, underpinning the longevity of hormetic fasting through orchestrating lipid catabolism and antioxidant defenses.

Indexed as

AntioxidantsCaenorhabditis elegansFastingHistonesHormesisLipid MetabolismLongevityAcetylationAnimalsCaenorhabditis elegans ProteinsReactive Oxygen SpeciesAntioxidantsCaenorhabditis elegans ProteinsHistonesReactive Oxygen Speciesagingantioxidant defenseCP: MetabolismCP: Molecular biologyepigenetic modificationfastinghistone acetylationlongevitymetabolic rewiringnuclear pore complexnutrient stress

Identifiers

PMID42258352

DOI10.1016/j.celrep.2026.117518

PMCPMC13528229

What OpenQuestion holds

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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.