VRK-1 extends life span by activation of AMPK via phosphorylation Park, Sangsoon Artan, Murat ; https://orcid.org/0000-0001-8945-6992 Han, Seung Hyun Park, Hae-Eun H. Jung, Yoonji Hwang, Ara B. Shin, Won Sik Kim, Kyong-Tai Lee, Seung-Jae V. ddc:570 Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans 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 vrk-1 in the soma of adult C. elegans increased life span and, conversely, inhibition of vrk-1 decreased life span. In addition, vrk-1 was required for longevity conferred by mutations that inhibit C. elegans mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both C. elegans 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 C. elegans and humans. American Association for the Advancement of Science 2020 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/15057 https://research-explorer.ista.ac.at/download/15057/15058 Park S, Artan M, Han SH, et al. VRK-1 extends life span by activation of AMPK via phosphorylation. <i>Science Advances</i>. 2020;6(27). doi:<a href="https://doi.org/10.1126/sciadv.aaw7824">10.1126/sciadv.aaw7824</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.aaw7824 info:eu-repo/semantics/altIdentifier/e-issn/2375-2548 info:eu-repo/semantics/openAccess