Distinct, common and synergistic effects of insulin and IGF-1 receptors on healthy murine ageing.

ABSTRACT:

Objective

Reduced IGF-1 signalling is an evolutionarily conserved mediator of longevity, yet the magnitude of this effect is substantially larger in organisms retaining a common insulin and IGF-1 receptor. Whether this reflects the failure to simultaneously reduce IGF-1 and insulin signalling in mammalian model systems remains unexplored, as is the associated impact on markers of healthy ageing. We set out to address these uncertainties.

Methods

We compared the duration of healthy life (healthspan) in male mice with haploinsufficiency of the insulin receptor (IRKO), IGF-1 receptor (IGF-1RKO), or both (DKO), versus wildtype (WT) littermates. Cognitive performance was defined using nesting studies at 3- and 24-months of age. Brain transcriptome was characterised at 3- and 18-m

SUBMITTER: Walker AM 

PROVIDER: S-EPMC11379992 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature