RRC ID 59525
Author Kumar S, Egan BM, Kocsisova Z, Schneider DL, Murphy JT, Diwan A, Kornfeld K.
Title Lifespan Extension in C. elegans Caused by Bacterial Colonization of the Intestine and Subsequent Activation of an Innate Immune Response.
Journal Dev Cell
Abstract Mechanisms that control aging are important yet poorly defined. To discover longevity control genes, we performed a forward genetic screen for delayed reproductive aging in C. elegans. Here, we show that am117 is a nonsense mutation in the phm-2 gene, which encodes a protein homologous to human scaffold attachment factor B. phm-2(lf) mutant worms have an abnormal pharynx grinder, which allows live bacteria to accumulate in the intestine. This defect shortens lifespan on highly pathogenic bacteria but extends lifespan and health span on the standard E. coli diet by activating innate immunity pathways that lead to bacterial avoidance behavior and dietary restriction. eat-2(lf) mutants displayed a similar phenotype, indicating accumulation of live bacteria also triggers extended longevity in this mutant. The analysis of phm-2 elucidates connections between pathogen response and aging by defining a mechanism of longevity extension in C. elegans-bacterial colonization, innate immune activation, and bacterial avoidance behavior.
Volume 49(1)
Pages 100-117.e6
Published 2019-4-8
DOI 10.1016/j.devcel.2019.03.010
PII S1534-5807(19)30187-X
PMID 30965033
PMC PMC6946027
MeSH Aging / genetics* Aging / immunology Animals Avoidance Learning / physiology Bacteria / immunology Bacteria / pathogenicity Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics* Diet Escherichia coli / chemistry Gene Expression Regulation / genetics Host-Pathogen Interactions / genetics Humans Immunity, Innate / genetics Intestines / microbiology Longevity / genetics* Longevity / immunology Receptors, Nicotinic / genetics*
IF 9.19
Times Cited 9
C.elegans tm1978