In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 3 ( 2023-3-16), p. e3002033-
Abstract:
Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits. Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002033
DOI:
10.1371/journal.pbio.3002033.g001
DOI:
10.1371/journal.pbio.3002033.g002
DOI:
10.1371/journal.pbio.3002033.g003
DOI:
10.1371/journal.pbio.3002033.g004
DOI:
10.1371/journal.pbio.3002033.g005
DOI:
10.1371/journal.pbio.3002033.g006
DOI:
10.1371/journal.pbio.3002033.g007
DOI:
10.1371/journal.pbio.3002033.t001
DOI:
10.1371/journal.pbio.3002033.t002
DOI:
10.1371/journal.pbio.3002033.s001
DOI:
10.1371/journal.pbio.3002033.s002
DOI:
10.1371/journal.pbio.3002033.s003
DOI:
10.1371/journal.pbio.3002033.s004
DOI:
10.1371/journal.pbio.3002033.s005
DOI:
10.1371/journal.pbio.3002033.s006
DOI:
10.1371/journal.pbio.3002033.s007
DOI:
10.1371/journal.pbio.3002033.s008
DOI:
10.1371/journal.pbio.3002033.s009
DOI:
10.1371/journal.pbio.3002033.s010
DOI:
10.1371/journal.pbio.3002033.s011
DOI:
10.1371/journal.pbio.3002033.s012
DOI:
10.1371/journal.pbio.3002033.s013
DOI:
10.1371/journal.pbio.3002033.s014
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10.1371/journal.pbio.3002033.s015
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10.1371/journal.pbio.3002033.s016
DOI:
10.1371/journal.pbio.3002033.s017
DOI:
10.1371/journal.pbio.3002033.s018
DOI:
10.1371/journal.pbio.3002033.s019
DOI:
10.1371/journal.pbio.3002033.s020
DOI:
10.1371/journal.pbio.3002033.s021
DOI:
10.1371/journal.pbio.3002033.s022
DOI:
10.1371/journal.pbio.3002033.s023
DOI:
10.1371/journal.pbio.3002033.s024
DOI:
10.1371/journal.pbio.3002033.s025
DOI:
10.1371/journal.pbio.3002033.s026
DOI:
10.1371/journal.pbio.3002033.s027
DOI:
10.1371/journal.pbio.3002033.s028
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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