dc.date.accessioned | 2022-04-21T16:32:14Z | |
dc.date.available | 2022-04-21T16:32:14Z | |
dc.date.created | 2021-09-10T19:33:56Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Venz, Richard Pekec, Tina Katic, Iskra Ciosk, Rafal Ewald, Collin Yves . End-of-life targeted auxin-mediated degradation of DAF-2 Insulin/IGF-1 receptor promotes longevity free from growth-related pathologies. eLIFE. 2021, 10 | |
dc.identifier.uri | http://hdl.handle.net/10852/93679 | |
dc.description.abstract | Preferably, lifespan-extending therapies should work when applied late in life without causing undesired pathologies. Reducing insulin/insulin-like growth factor (IGF)-1 signaling (IIS) increases lifespan across species, but the effects of reduced IIS interventions in extreme geriatric ages remains unknown. Using the nematode Caenorhabditis elegans , we engineered the conditional depletion of the DAF-2/insulin/IGF-1 transmembrane receptor using an auxin-inducible degradation (AID) system. This allowed for the temporal and spatial reduction in DAF-2 protein levels at time points after which interventions such as RNAi become ineffective. Using this system, we found that AID-mediated depletion of DAF-2 protein surpasses the longevity of daf-2 mutants. Depletion of DAF-2 during early adulthood resulted in multiple adverse phenotypes, including growth retardation, germline shrinkage, egg retention, and reduced brood size. By contrast, AID-mediated depletion of DAF-2 post-reproduction, or specifically in the intestine in early adulthood, resulted in an extension of lifespan without these deleterious effects. Strikingly, at geriatric ages, when 75% of the population had died, AID-mediated depletion of DAF-2 protein resulted in a doubling in lifespan. Thus, we provide a proof-of-concept that even close to the end of an individual’s lifespan, it is possible to slow aging and promote longevity. | |
dc.language | EN | |
dc.publisher | eLife Sciences Publications Ltd | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | End-of-life targeted auxin-mediated degradation of DAF-2 Insulin/IGF-1 receptor promotes longevity free from growth-related pathologies | |
dc.type | Journal article | |
dc.creator.author | Venz, Richard | |
dc.creator.author | Pekec, Tina | |
dc.creator.author | Katic, Iskra | |
dc.creator.author | Ciosk, Rafal | |
dc.creator.author | Ewald, Collin Yves | |
cristin.unitcode | 185,15,29,40 | |
cristin.unitname | Seksjon for biokjemi og molekylærbiologi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1933390 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=eLIFE&rft.volume=10&rft.spage=&rft.date=2021 | |
dc.identifier.jtitle | eLIFE | |
dc.identifier.volume | 10 | |
dc.identifier.doi | https://doi.org/10.7554/eLife.71335 | |
dc.identifier.urn | URN:NBN:no-96253 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2050-084X | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/93679/1/End-of-life%2Btargeted%2Bdegradation%2B-elife-71335-v2.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | e71335 | |
dc.relation.project | NFR/286499 | |