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Updated: Aug 6, 2025

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
Published on: November 14, 2013
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.
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.
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