Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature communications, 2023-01, Vol.14 (1), p.288-288, Article 288

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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 1 H-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 Aβ 42 . 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.