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

Autor:	Stevenson ME; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Bieri G; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Bakar Aging Research Institute, San Francisco, CA 94143, USA., Kaletsky R; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., St Ange J; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Remesal L; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Bakar Aging Research Institute, San Francisco, CA 94143, USA., Pratt KJB; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Bakar Aging Research Institute, San Francisco, CA 94143, USA., Zhou S; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Weng Y; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Murphy CT; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: ctmurphy@princeton.edu., Villeda SA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Bakar Aging Research Institute, San Francisco, CA 94143, USA. Electronic address: saul.villeda@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Sep 26; Vol. 42 (9), pp. 113151. Date of Electronic Publication: 2023 Sep 19.
DOI:	10.1016/j.celrep.2023.113151
Abstrakt:	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. 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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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