Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.
Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.
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DOI：
10.1016/j.cell.2015.02.004
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发表时间：
2015-02-26
期刊：
影响因子：
64.5
通讯作者：
Mair WB
中科院分区：
文献类型：
--
作者：
Burkewitz K;Morantte I;Weir HJM;Yeo R;Zhang Y;Huynh FK;Ilkayeva OR;Hirschey MD;Grant AR;Mair WB
Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell-nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging.
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DOI：
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发表时间：
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期刊：
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DOI：
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发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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影响因子：
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