Evidence map›Paper›PMID 42162381›Full record

ArticleNature aging2026

Peroxisomes orchestrate metabolic flexibility and longevity via an interorganelle cascade.

Arpit Sharma, Aditi Prabhakar, Miriam Valera-Alberni, Jamie D Kraft, Abigail E Ellis, Ryan D Sheldon, Meeta Mistry, Pallas Yao, Yanshan Liang, Sheng Hui and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature aging, 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.

  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

11 authors.

Arpit SharmaDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Aditi Prabhakar *Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6024-4600
Miriam Valera-Alberni *Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Jamie D KraftDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Abigail E EllisMass Spectrometry Core, Van Andel Institute, Grand Rapids, MI, USA.ORCID http://orcid.org/0000-0002-8736-8283
Ryan D SheldonMass Spectrometry Core, Van Andel Institute, Grand Rapids, MI, USA.ORCID http://orcid.org/0000-0002-1573-9719
Meeta MistryHarvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Pallas YaoDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Yanshan LiangDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Sheng HuiDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
William B MairDepartment of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. wmair@hsph.harvard.edu.ORCID http://orcid.org/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
Reversing Loss of Metabolic Homeostasis to Ameliorate Alzheimer's Disease PathogenicityR01AG067106 · NIA · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI MAIR, WILLIAM B · 2020 to 2024
$2.0M
Targeting Mechanisms of Organelle Remodeling to Promote Healthy AgingR00AG078343 · NIA · TUFTS UNIVERSITY BOSTON · PI Arpit Sharma · 2025 to 2026
$489k
Targeting Mechanisms of Organelle Remodeling to Promote Healthy AgingK99AG078343 · NIA · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI SHARMA, ARPIT · 2023 to 2024
$259k
NIA NIH HHS K99 AG078343NIA NIH HHS R00 AG078343U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) K99AG078343U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R00AG078343U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG044346U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG067106
6 · The paper itself

Abstract

Aging impairs coordinated organelle dynamics essential for lipid metabolism, causing a decline in intracellular metabolic flexibility. However, the drivers of organelle collapse and their temporal order remain unclear. Here we identify peroxisomal function as a critical regulator of metabolic flexibility during youth and low-energy states. Using Caenorhabditis elegans, we show that fasting robustly induces peroxisomal function in youth, whereas this response is blunted during aging. Loss of peroxisomal import via PRX-5 declines over age, causing pathological lipid droplet expansion, dysfunctional mitochondrial bioenergetics and metabolic inflexibility. Although targeted PRX-5 degradation recapitulates metabolic aging, its overexpression preserves lipid dynamics and mitochondrial integrity. Notably, dietary restriction maintains peroxisomal pathways and organelle coordination into late life and peroxisomal function causally underpins dietary restriction-mediated longevity. Our findings highlight peroxisomes as central upstream regulators of a dynamic interorganelle cascade driving metabolic plasticity and highlight peroxisomal maintenance as a key determinant of metabolic flexibility during aging.

Indexed as

AgingCaenorhabditis elegansLongevityPeroxisomesAnimalsCaenorhabditis elegans ProteinsCaloric RestrictionEnergy MetabolismLipid MetabolismMitochondriaCaenorhabditis elegans Proteins

Identifiers

PMID42162381
PMCPMC13190317

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.