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 PMID:37713310  

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

Morgan E Stevenson | Gregor Bieri | Rachel Kaletsky | Jonathan St Ange | L Remesal | Karishma J B Pratt | Shiyi Zhou | Yifei Weng | Coleen T Murphy | Saul A Villeda
Cell reports | 2023

Loss of cognitive function with age is devastating. EGL-30/GNAQ and Gαq 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. elegans is a powerful model to identify mammalian regulators of memory, leading to the identification of a pathway that improves memory in extremely old mice. To our knowledge, this is the oldest age at which an intervention has improved age-related cognitive decline.

Pubmed ID: 37713310

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: DP1 AG077430
  • Agency: NIA NIH HHS, United States
    Id: F32 AG079490
  • Agency: NIA NIH HHS, United States
    Id: F32 AG081038
  • Agency: NIA NIH HHS, United States
    Id: R01 AG077816

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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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