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Hypothalamic Menin regulates systemic aging and cognitive decline.
Lige Leng1, Ziqi Yuan1, Xiao Su1
1Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian, China.
Plos Biology
|March 17, 2023
Summary
Hypothalamic Menin signaling is crucial for healthy aging. Restoring Menin in aged mice extended lifespan and improved cognition, highlighting its role in systemic aging and cognitive decline.
Area of Science:
- Neuroscience
- Gerontology
- Molecular Biology
Background:
- Aging is a complex systemic process linked to functional decline and mortality.
- The molecular underpinnings of aging and associated cognitive deficits remain incompletely understood.
- The hypothalamus regulates systemic aging via neuroinflammatory signaling, with Menin implicated in brain development and neuroinflammation.
Purpose of the Study:
- To investigate the role of hypothalamic Menin signaling in aging and cognitive decline.
- To determine if modulating Menin in the ventromedial nucleus of the hypothalamus (VMH) impacts aging processes and lifespan.
Main Methods:
- Analysis of hypothalamic Menin signaling in aged mice.
- Restoration of Menin expression in the VMH of aged mice and inhibition in middle-aged mice.
- Epigenetic analysis of Menin's regulatory pathways, including neuroinflammation and D-serine metabolism.
- Assessment of lifespan, cognitive function (learning and memory), and aging biomarkers.
Main Results:
- Hypothalamic Menin signaling diminishes with age, correlating with systemic aging and cognitive impairment.
- Restoring VMH Menin in aged mice extended lifespan, improved cognition, and ameliorated aging markers.
- Inhibiting VMH Menin in middle-aged mice accelerated aging and cognitive decline.
- Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism.
- Aging-associated Menin reduction impaired VMH-hippocampus neural circuit D-serine release; D-serine supplementation rescued cognitive deficits.
Conclusions:
- Ventromedial nucleus of the hypothalamus (VMH) Menin is a critical regulator of systemic aging and age-related cognitive decline.
- Menin's function involves epigenetic regulation of neuroinflammation and D-serine metabolism.
- Targeting VMH Menin signaling offers a potential therapeutic strategy for mitigating aging and cognitive impairment.
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