VRK-1 extends life span by activation of AMPK via phosphorylation

Abstract

Vaccinia virus-related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single <i>Caenorhabditis elegans</i> VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein kinase (AMPK), via direct phosphorylation. We found that overexpression of <i>vrk-1</i> in the soma of adult <i>C. elegans</i> increased life span and, conversely, inhibition of <i>vrk-1</i> decreased life span. In addition, <i>vrk-1</i> was required for longevity conferred by mutations that inhibit <i>C. elegans</i> mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both <i>C. elegans</i> and cultured human cells. Thus, our data show that the somatic nuclear kinase, VRK-1, promotes longevity through AMPK activation, and this function appears to be conserved between <i>C. elegans</i> and humans.