AMPK modulates tissue and organismal aging in a non-cell-autonomous manner.
AMPK modulates tissue and organismal aging in a non-cell-autonomous manner.
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DOI：
10.1016/j.celrep.2014.08.006
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发表时间：
2014-09-25
期刊：
影响因子：
8.8
通讯作者：
Walker DW
中科院分区：
文献类型：
--
作者：
Ulgherait M;Rana A;Rera M;Graniel J;Walker DW
AMPK在多种物种中发挥促长寿作用；然而，所涉及的组织特异性机制尚不清楚。在这里，我们发现AMPK在成年果蝇神经系统中的上调可诱导大脑和肠上皮的自噬。自噬的诱导与衰老和延长寿命期间肠道稳态的改善有关。神经元上调自噬特异性蛋白激酶Atg1是诱导衰老过程中这些组织间效应和延长寿命的必要和充分条件。此外，成人肠道中AMPK的上调可诱导大脑细胞自主和非自主的自噬，减缓全身衰老并延长寿命。我们发现，机体对组织特异性AMPK/Atg1激活的反应与大脑中胰岛素样肽水平的降低和4E-BP表达的全身性增加有关。总之，这些结果揭示了关键组织中AMPK和/或Atg1的局部激活可以以细胞非自主的方式延缓衰老。
AMPK exerts pro-longevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that up-regulation 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 up-regulation of the autophagy-specific protein kinase Atg1 is both necessary and sufficient to induce these inter-tissue effects during aging and to prolong lifespan. Furthermore, up-regulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-autonomously in the brain, slows systemic aging and prolongs 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 cell-non-autonomous manner.
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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
4.5
作者：
Biteau B;Karpac J;Supoyo S;Degennaro M;Lehmann R;Jasper H
通讯作者：
Jasper H
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
4.5
作者：
Bai H;Kang P;Hernandez AM;Tatar M
通讯作者：
Tatar M