한빛사논문
- 조회334
한국생명공학연구원
Jin-Hyuck Jeong1,2,7, Jun-Seok Han1,7, Youngae Jung3,7, Seung-Min Lee1, So-Hyun Park1,2, Mooncheol Park1, Min-Gi Shin1, Nami Kim3, Mi Sun Kang3, Seokho Kim4, Kwang-Pyo Lee 1,2, Ki-Sun Kwon1,5, Chun-A. Kim1, Yong Ryoul Yang1, Geum-Sook Hwang3,6 & Eun-Soo Kwon1
1Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
2Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Korea.
3Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Korea.
4Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Korea.
5Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Korea.
6Department of Chemistry & Nano Science, Ewha Womans University, Seoul 03760, Korea.
7These authors contributed equally: Jin-Hyuck Jeong, Jun-Seok Han, Youngae Jung.
Corresponding authors
Correspondence to Geum-Sook Hwang or Eun-Soo Kwon.
Abstract
Dietary restriction (DR) delays aging and the onset of age-associated diseases. However, it is yet to be determined whether and how restriction of specific nutrients promote longevity. Previous genome-wide screens isolated several Escherichia coli mutants that extended lifespan of Caenorhabditis elegans. Here, using 1H-NMR metabolite analyses and inter-species genetics, we demonstrate that E. coli mutants depleted of intracellular glucose extend C. elegans lifespans, serving as bona fide glucose-restricted (GR) diets. Unlike general DR, GR diets don't reduce the fecundity of animals, while still improving stress resistance and ameliorating neuro-degenerative pathologies of Aβ42. Interestingly, AAK-2a, a new AMPK isoform, is necessary and sufficient for GR-induced longevity. AAK-2a functions exclusively in neurons to modulate GR-mediated longevity via neuropeptide signaling. Last, we find that GR/AAK-2a prolongs longevity through PAQR-2/NHR-49/Δ9 desaturases by promoting membrane fluidity in peripheral tissues. Together, our studies identify the molecular mechanisms underlying prolonged longevity by glucose specific restriction in the context of whole animals.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-03-15)
- 국내 연구진
- 생명과학 > 노화/암생물학
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