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A decline in p38 MAPK signaling underlies immunosenescence in Caenorhabditis elegans.

Matthew J Youngman | Zoë N Rogers | Dennis H Kim
PLoS genetics | 2011

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.

Pubmed ID: 21625567

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM084477
  • Agency: NIGMS NIH HHS, United States
    Id: R01-GM084477

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The Burroughs Wellcome Fund is an independent private foundation dedicated to advancing the biomedical sciences by supporting research and other scientific and educational activities. Within this broad mission, BWF has two primary goals: * To help scientists early in their careers develop as independent investigators * To advance fields in the basic biomedical sciences that are undervalued or in need of particular encouragement BWF''s financial support is channeled primarily through competitive peer-reviewed award programs. * BWF''s endowment: $586.8 million at the end of FY 2009 * BWF approved $26.4 million in grants during FY 2009 BWF makes grants primarily to degree-granting institutions on behalf of individual researchers, who must be nominated by their institutions. To complement these competitive award programs, BWF also makes grants to nonprofit organizations conducting activities intended to improve the general environment for science. A Board of Directors comprising distinguished scientists and business leaders governs BWF. BWF was founded in 1955 as the corporate foundation of the pharmaceutical firm Burroughs Wellcome Co. In 1993, a generous gift from the Wellcome Trust in the United Kingdom, enabled BWF to become fully independent from the company, which was acquired by Glaxo in 1995. BWF has no affiliation with any corporation.

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