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AMPK modulates tissue and organismal aging in a non-cell-autonomous manner.

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ulgherait M,Rana A,Rera M,Graniel J,Walker DW

doi

10.1016/j.celrep.2014.08.006

subject

Has Abstract

pub_date

2014-09-25 00:00:00

pages

1767-1780

issue

6

issn

2211-1247

pii

S2211-1247(14)00669-X

journal_volume

8

pub_type

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