دورية أكاديمية
أعرض في EDS

Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans .

التفاصيل البيبلوغرافية
العنوان: Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans .
المؤلفون: Zhang Y; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Lanjuin A; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Chowdhury SR; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Mistry M; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Silva-García CG; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Weir HJ; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Lee CL; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States.; Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan., Escoubas CC; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States.; Faculty of Medicine, Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France., Tabakovic E; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States., Mair WB; Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States.
المصدر: ELife [Elife] 2019 Aug 14; Vol. 8. Date of Electronic Publication: 2019 Aug 14.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Longevity* , Mitochondrial Dynamics*, Caenorhabditis elegans/*enzymology , Caenorhabditis elegans/*physiology , Mechanistic Target of Rapamycin Complex 1/*metabolism , Protein Kinases/*metabolism, AMP-Activated Protein Kinase Kinases ; Animals
مستخلص: Target of rapamycin complex 1 (TORC1) and AMP-activated protein kinase (AMPK) antagonistically modulate metabolism and aging. However, how they coordinate to determine longevity and if they act via separable mechanisms is unclear. Here, we show that neuronal AMPK is essential for lifespan extension from TORC1 inhibition, and that TORC1 suppression increases lifespan cell non autonomously via distinct mechanisms from global AMPK activation. Lifespan extension by null mutations in genes encoding raga-1 (RagA) or rsks-1 (S6K) is fully suppressed by neuronal-specific rescues. Loss of RAGA-1 increases lifespan via maintaining mitochondrial fusion. Neuronal RAGA-1 abrogation of raga-1 mutant longevity requires UNC-64/syntaxin, and promotes mitochondrial fission cell nonautonomously. Finally, deleting the mitochondrial fission factor DRP-1 renders the animal refractory to the pro-aging effects of neuronal RAGA-1. Our results highlight a new role for neuronal TORC1 in cell nonautonomous regulation of longevity, and suggest TORC1 in the central nervous system might be targeted to promote healthy aging.
Competing Interests: YZ, AL, SC, MM, CS, HW, CL, CE, ET, WM No competing interests declared
(© 2019, Zhang et al.)
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معلومات مُعتمدة: R21 AG056930 United States AG NIA NIH HHS; 1R01AG059595 International National Institute for Aging; R01 AG059595 United States AG NIA NIH HHS; 1R01AG059595 United States AG NIA NIH HHS; R01 AG044346 United States AG NIA NIH HHS; 1R01AG044346 United States AG NIA NIH HHS; 1R01AG044346 International National Institute for Aging
فهرسة مساهمة: Keywords: AMPK; C. elegans; TORC1; aging; genetics; genomics; mitochondria
سلسلة جزيئية: GEO GSE132794
المشرفين على المادة: EC 2.7.- (Protein Kinases)
EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
تواريخ الأحداث: Date Created: 20190815 Date Completed: 20200203 Latest Revision: 20211204
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6713509
DOI: 10.7554/eLife.49158
PMID: 31411562
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.49158