title: A decline in p38 MAPK signaling underlies immunosenescence in Caenorhabditis elegans.
abstract: The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Youngman
authors.forename: Zoë N
authors.initials: ZN
authors.lastname: Rogers
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans