AMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner
Year: 2014
Type: article
Abstract: AMPK exerts prolongevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that upregulation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and also in the intestinal epithelium. Induction of autophagy is linked to improved intestinal homeostasis during aging and extended lifespan. Neuronal upregulation of the autophagy-specific protein kinase Atg1 is both necessary and sufficient to induce these intertissue effects during aging and to prolong the lifespan. Furthermore, upregulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-cell-autonomously in the brain, slows systemic aging, and prolongs the lifespan. We show that the organism-wide response to tissue-specific AMPK/Atg1 activation is linked to reduced insulin-like peptide levels in the brain and a systemic increase in 4E-BP expression. Together, these results reveal that localized activation of AMPK and/or Atg1 in key tissues can slow aging in a non-cell-autonomous manner.
Source: Cell Reports
Authors: Matthew Ulgherait, Anil Rana, Michael Rera, Jacqueline Graniel, David W. Walker
Institution: University of California, Los Angeles
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Metabolic regulation of stem cell behavior and longevity, University of Michigan Postbaccalaureate Research Education Program (UM PREP), MARC U*STAR Program at the University of California, Los Angeles, Research Tranining in Cellular and Molecular Biology, Career Training in the Biology of Aging, Role of Mitochondrial Homeostasis in Animal Aging
OpenAlex ID: W2006776535