Age-related changes in AMPK activation: Role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways.

Age-related changes in AMPK activation: Role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways.
Ageing Res Rev. 2016 Apr 6;
Authors: Salminen A, Kaarniranta K, Kauppinen A
Abstract
AMP-activated protein kinase (AMPK) is a fundamental regulator of energy metabolism, stress resistance, and cellular proteostasis. AMPK signaling controls an integrated signaling network which is involved in the regulation of healthspan and lifespan e.g. via FoxO, mTOR/ULK1, CRCT-1/CREB, and SIRT1 signaling pathways. Several studies have demonstrated that the activation capacity of AMPK signaling declines with aging, which impairs the maintenance of efficient cellular homeostasis and enhances the aging process. However, it seems that the aging process affects AMPK activation in a context-dependent manner since occasionally, it can also augment AMPK activation, possibly attributable to the type of insult and tissue homeostasis. Three protein phosphatases, PP1, PP2A, and PP2C, inhibit AMPK activation by dephosphorylating the Thr172 residue of AMPKα, required for AMPK activation. In addition, several upstream signaling pathways can phosphorylate Ser/Thr residues in the β/γ interaction domain of the AMPKα subunit that subsequently blocks the activation of AMPK. These inhibitory pathways include the insulin/AKT, cyclic AMP/PKA, and RAS/MEK/ERK pathways. We will examine the evidence whether the efficiency of AMPK responsiven...

Source: Ageing Research Reviews - April 5, 2016 Category: Genetics & Stem Cells Authors: Salminen A, Kaarniranta K, Kauppinen A Tags: Ageing Res Rev Source Type: research