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- Title
A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity.
- Authors
Jeong, Jin-Hyuck; Han, Jun-Seok; Jung, Youngae; Lee, Seung-Min; Park, So-Hyun; Park, Mooncheol; Shin, Min-Gi; Kim, Nami; Kang, Mi Sun; Kim, Seokho; Lee, Kwang-Pyo; Kwon, Ki-Sun; Kim, Chun-A.; Yang, Yong Ryoul; Hwang, Geum-Sook; Kwon, Eun-Soo
- 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.Although diet modulates aging, little is known about whether and how nutrient regulates longevity. Here, the authors show that glucose-restricted diets prolong longevity through series of conserved factors, such as neuronal AMPK, neuropeptide, AdipoR, PPARα, and Δ9 desaturases by promoting membrane fluidity.
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-35952-z