Evidence map›Paper›PMID 27133168›Full record

ArticleCell2016

Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity.

Carsten Merkwirth, Virginija Jovaisaite, Jenni Durieux, Olli Matilainen, Sabine D Jordan, Pedro M Quiros, Kristan K Steffen, Evan G Williams, Laurent Mouchiroud, Sarah U Tronnes and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers.

0numbers the graph read from it
0cells of the map it votes in
235citing papers in PubMed
20.3field-weighted citation impact, top 1% of its field
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

235 citing papers in PubMed, 363 citations in OpenAlex.

  1. Article
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  7. A Forward Genetic Screen inbioRxiv : the preprint server for biology · 2026
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  9. Perturbation of mitochondrial CaStress biology · 2026
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175 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Carsten MerkwirthHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Glenn Center for Research on Aging, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA.
Virginija JovaisaiteLaboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Jenni DurieuxHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA.
Olli MatilainenLaboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Sabine D JordanHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Pedro M QuirosLaboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Kristan K SteffenHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA.
Evan G WilliamsLaboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Laurent MouchiroudLaboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Sarah U TronnesHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA.
Virginia MurilloThe Glenn Center for Research on Aging, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Suzanne C WolffHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA.
Reuben J ShawThe Glenn Center for Research on Aging, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Johan AuwerxLaboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland. Electronic address: admin.auwerx@epfl.ch.
Andrew DillinHoward Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: dillin@berkeley.edu.
École Polytechnique Fédérale de Lausanne · CHHoward Hughes Medical Institute · USSalk Institute for Biological Studies · USUniversity of California, Berkeley · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
Neuroendocrine Coordination of Mitochondrial Stress Signaling and ProteostasisR01ES021667 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI DILLIN, ANDREW G · 2012 to 2023
$4.6M
Translational Systems Genetics of Mitochondria, Metabolism, and AgingR01AG043930 · NIA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI WILLIAMS, ROBERT W. · 2013 to 2017
$2.5M
Genome Sequencer FLXS10RR029668 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI NGAI, JOHN J. · 2010 to 2010
$623k
Illumina Sequencer to Facilitate Functional Genomics at BerkeleyS10RR027303 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI TAYLOR, JOHN W. · 2010 to 2010
$500k
NCI NIH HHS P30 CA014195NCRR NIH HHS S10 RR027303NCRR NIH HHS S10 RR029668NIA NIH HHS R01 AG043930NIEHS NIH HHS R01 ES021667NIH HHS P40 OD010440
6 · The paper itself

Abstract

Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPR(mt) signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. We identify the conserved histone lysine demethylases jmjd-1.2/PHF8 and jmjd-3.1/JMJD3 as positive regulators of lifespan in response to mitochondrial dysfunction across species. Reduction of function of the demethylases potently suppresses longevity and UPR(mt) induction, while gain of function is sufficient to extend lifespan in a UPR(mt)-dependent manner. A systems genetics approach in the BXD mouse reference population further indicates conserved roles of the mammalian orthologs in longevity and UPR(mt) signaling. These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations.

Indexed as

AnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsHistone DemethylasesJumonji Domain-Containing Histone DemethylasesLongevityMiceMitochondriaTranscription FactorsTranscription, GeneticUnfolded Protein ResponseCaenorhabditis elegans ProteinsHistone DemethylasesJMJD-1.2 protein, C elegansJMJD-3.1 protein, C elegansJumonji Domain-Containing Histone DemethylasesKdm6b protein, mousePHF8 protein, mouseTranscription Factors

Identifiers

PMID27133168
PMCPMC4889222
OpenAlexW2343257250

What OpenQuestion holds

Textmetadata
LicenceTDM
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.