Neuronal activation of G_αq EGL-30/GNAQ late in life rejuvenates cognition across species.

ABSTRACT: Loss of cognitive function with age is devastating. EGL-30/GNAQ and G_αq signaling pathways are highly conserved between C. elegans and mammals, and murine Gnaq is enriched in hippocampal neurons and declines with age. We found that activation of EGL-30 in aged worms triples memory span, and GNAQ gain of function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice (equivalent to 70- to 80-year-old humans) rescued age-related impairments in well-being and memory. Single-nucleus RNA sequencing revealed increased expression of genes regulating synaptic function, axon guidance, and memory in GNAQ-treated mice, and worm orthologs of these genes were required for long-term memory extension in worms. These experiments demonstrate that C. eleg

SUBMITTER: Stevenson ME 

PROVIDER: S-EPMC10627507 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature