A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity

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Title
A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity
Author(s)
Jin Hyuk Jeong; Jun Seok Han; Y Jung; Seung-Min Lee; So Hyun Park; Mooncheol Park; Min-Gi Shin; N Kim; M S Kang; S Kim; Kwang-Pyo LeeKi-Sun KwonChuna KimYong Ryoul Yang; G S Hwang; Eun-Soo Kwon
Bibliographic Citation
Nature Communications, vol. 14, pp. 288-288
Publication Year
2023
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.
ISSN
2041-1723
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41467-023-35952-z
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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