Mutation of an insulin-sensitive <i>Drosophila</i> insulin-like receptor mutant requires methionine metabolism reprogramming to extend lifespan.

ABSTRACT: Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan across many species. Multiple mechanisms are proposed for how this altered signaling slows aging. To elaborate these causes, we recently developed a series of Drosophila insulin-like receptor (dInr) mutants with single amino acid substitutions that extend lifespan but differentially affect insulin sensitivity, growth and reproduction. Transheterozygotes of canonical dInr mutants (Type I) extend longevity and are insulin-resistant, small and weakly fecund. In contrast, a dominant mutation (dInr ³⁵³, Type II) within the Kinase Insert Domain (KID) robustly extends longevity but is insulin-sensitive, full-sized, and highly fecund. We applied transcriptome and metabolome

SUBMITTER: Tatar M 

PROVIDER: S-EPMC11908128 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature