دورية أكاديمية
End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies
| العنوان: | End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies |
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| المؤلفون: | Venz, Richard, Pekec, Tina, Katic, Iskra, Ciosk, Rafal, Ewald, Collin Yvès |
| المساهمون: | Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Research Council of Norway |
| المصدر: | eLife ; volume 10 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2021 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.71335 |
| الإتاحة: | https://doi.org/10.7554/elife.71335Test https://cdn.elifesciences.org/articles/71335/elife-71335-v2.pdfTest https://cdn.elifesciences.org/articles/71335/elife-71335-v2.xmlTest https://elifesciences.org/articles/71335Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ ; http://creativecommons.org/licenses/by/4.0Test/ ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.9333ABCE |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.71335 |
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