Evidence map›Paper›PMID 38900346›Full record

ArticleGeroScience2024

Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age.

Adrian Molière, Ji Young Cecilia Park, Anita Goyala, Elena M Vayndorf, Bruce Zhang, Kuei Ching Hsiung, Yoonji Jung, Sujeong Kwon, Cyril Statzer, David Meyer and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in GeroScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Condition-dependent effects of knockdown of autophagy onbioRxiv : the preprint server for biology · 2025
    Article
  10. 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

21 authors.

Adrian MolièreLaboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, CH-8603, Schwerzenbach, Switzerland.
Ji Young Cecilia ParkLaboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, CH-8603, Schwerzenbach, Switzerland.
Anita GoyalaLaboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, CH-8603, Schwerzenbach, Switzerland.
Elena M VayndorfDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195-7470, USA.
Bruce ZhangInstitute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London, UK.
Kuei Ching HsiungInstitute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London, UK.
Yoonji JungDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
Sujeong KwonDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
Cyril StatzerLaboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, CH-8603, Schwerzenbach, Switzerland.
David MeyerInstitute for Genome Stability in Aging and Disease, Medical Faculty, University Hospital and University of Cologne, Joseph-Stelzmann-Str. 26, 50931, Cologne, Germany.
Richard NguyenDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195-7470, USA.
Joseph ChadwickThe Babraham Institute, Cambridge, UK.
Maximilian A ThompsonThe Babraham Institute, Cambridge, UK.
Björn SchumacherInstitute for Genome Stability in Aging and Disease, Medical Faculty, University Hospital and University of Cologne, Joseph-Stelzmann-Str. 26, 50931, Cologne, Germany.
Seung-Jae V LeeDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
Clara L EssmannBioinformatics and Molecular Genetics, Institute of Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79108, Freiburg, Germany.
Michael R MacArthurLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, 08540, USA.
Matt KaeberleinDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195-7470, USA.
Della DavidThe Babraham Institute, Cambridge, UK.
David GemsInstitute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London, UK.
Collin Y EwaldLaboratory of Extracellular Matrix Regeneration, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, CH-8603, Schwerzenbach, Switzerland. collin-ewald@ethz.ch.ORCID 0000-0003-1166-4171

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
NIH HHS P40 OD010440Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 190072
6 · The paper itself

Abstract

Little is known about the possibility of reversing age-related biological changes when they have already occurred. To explore this, we have characterized the effects of reducing insulin/IGF-1 signaling (IIS) during old age. Reduction of IIS throughout life slows age-related decline in diverse species, most strikingly in the nematode Caenorhabditis elegans. Here we show that even at advanced ages, auxin-induced degradation of DAF-2 in single tissues, including neurons and the intestine, is still able to markedly increase C. elegans lifespan. We describe how reversibility varies among senescent changes. While senescent pathologies that develop in mid-life were not reversed, there was a rejuvenation of the proteostasis network, manifesting as a restoration of the capacity to eliminate otherwise intractable protein aggregates that accumulate with age. Moreover, resistance to several stressors was restored. These results support several new conclusions. (1) Loss of resilience is not solely a consequence of pathologies that develop in earlier life. (2) Restoration of proteostasis and resilience by inhibiting IIS is a plausible cause of the increase in lifespan. And (3), most interestingly, some aspects of the age-related transition from resilience to frailty can be reversed to a certain extent. This raises the possibility that the effect of IIS and related pathways on resilience and frailty during aging in higher animals might possess some degree of reversibility.

Indexed as

AgingCaenorhabditis elegansCaenorhabditis elegans ProteinsLongevityProteostasisReceptor, InsulinSignal TransductionAnimalsInsulinInsulin-Like Growth Factor ICaenorhabditis elegans ProteinsDAF-2 protein, C elegansInsulinInsulin-Like Growth Factor IReceptor, InsulinEnd-of-lifeFrailtyInsulin/IGF-1 signalingLongevityProtein homeostasisResilience

Identifiers

PMID38900346
PMCPMC11335714

What OpenQuestion holds

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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.