Evidence map›Paper›PMID 40501628›Full record

ArticlebioRxiv : the preprint server for biology2025

The longevity effects of reduced IGF-1 signaling depend on the stability of the mitochondrial genome.

Sarah J Shemtov, Eric McGann, Lucy Carrillo, Sangmin Lee, Herbert Anson, Claire S Chung, Maria-Eleni Anagnostou, Guan-Ju D Lai, Bert M Verheijen, Junxiang Wan and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Sarah J ShemtovLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-8176-1105
Eric McGannLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Lucy CarrilloLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Sangmin LeeLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Herbert AnsonLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Claire S ChungLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Maria-Eleni AnagnostouLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Guan-Ju D LaiDepartment of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY, USA.
Bert M VerheijenDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Junxiang WanLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Ivetta VorobyovaLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Monica Sanchez-ContrerasDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3092-2781
Cheryl A ConoverDivision of Endocrinology, Metabolism and Nutrition, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-4550-6633
Max A ThorwaldLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0003-0095-5344
Pinchas CohenLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-0035-8366
Scott R KennedyDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-4444-1145
Jean-François GoutDepartment of Biological Sciences, Mississippi State University, Starkville, MS, USA.ORCID 0000-0002-4549-5647
Suraiya HaroonPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-5575-4609
Marc VermulstLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.

Funding

Investigating the landscape and genetic architecture of germline mutagenesisR35GM133428 · NIGMS · UNIVERSITY OF WASHINGTON · PI Kelley Harris · 2019 to 2026
$2.8M
Temporal control of mitochondrial mutagenesisR01AG075130 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Marc Vermulst · 2022 to 2026
$2.6M
DNA-damage-induced transcription errors provide a constant stream of amyloid and prion-like proteins in human cellsR01AG083065 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Marc Vermulst · 2024 to 2026
$2.1M
Targeting the IGF-1/insulin signaling pathway to treat mtDNA diseaseR01GM124532 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VERMULST, MARC · 2017 to 2020
$1.2M
Triggering the Selective Removal of Deleterious mtDNA Mutations from Mammalian CellsF31AG084238 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SHEMTOV, SARAH JEAN · 2024 to 2024
$49k
NIA NIH HHS F31 AG084238NIA NIH HHS R01 AG075130NIA NIH HHS R01 AG083065NIGMS NIH HHS R01 GM124532NIGMS NIH HHS R35 GM133428
6 · The paper itself

Abstract

Suppression of insulin-like growth factor-1 (IGF-1) signaling extends mammalian lifespan and protects against a range of age-related diseases. Surprisingly though, we found that reduced IGF-1 signaling fails to extend the lifespan of mitochondrial mutator mice. Accordingly, most of the longevity pathways that are normally initiated by IGF-1 suppression were either blocked or blunted in the mutator mice. These observations suggest that the pro-longevity effects of IGF-1 suppression critically depend on the integrity of the mitochondrial genome and that mitochondrial mutations may impose a hard limit on mammalian lifespan. Together, these findings deepen our understanding of the interactions between the hallmarks of aging and underscore the need for interventions that preserve the integrity of the mitochondrial genome.

Identifiers

PMID40501628
PMCPMC12157428

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Registered trials

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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.