![]() VMH microinflammation has been tightly linked to the metabolic mode of macronutrients, especially the fatty acid-mediated oxidative metabolism. Activation of IKKβ/NF-κB signaling tunes down gonadotropin-releasing hormone (GnRH) release in the hypothalamus during aging, while GnRH supplement alleviates aging-impaired neurogenesis and decelerates aging.īesides aging, VMH is critical in regulating food intake and maintaining whole-body energy metabolic, glucose, and lipid balance. RelA (p65) phosphorylation, marker of NF-κB activation, increases gradually during aging. Specifically, neuroinflammatory IKKβ/NF-κB signaling in ventromedial hypothalamus (VMH) is defined as the pace-regulator of systemic aging. Among brain and the sub brain region, hypothalamus has been identified as critical central regulators of aging process. Partial least-square discriminant analysis PRR,Īging is characterized by the progressive and overall deterioration of physiological functions, leading to the end of an organism’s lifespan. Orthogonal partial least-square discriminant analysis PCA, Miniature inhibitory postsynaptic current MRM, ![]() ![]() Miniature excitatory postsynaptic current mIPSC, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.ĭamage-associated molecular pattern DEG, Grant:8180131520 to L.L.) The National Key Research and Development Program of China (Grant: 2021YFA1101402 to J.Z.) The Fundamental Research Funds for the Central Universities (Grant: 2072019010180049 to J.Z.) Xiamen Municipal Health Commission, Xiamen Municipal Bureau of Science and Technology (3502Z20209005) Fujian Province Nature Science Foundation (Grant: 2019J05006 to L.L.) Xiamen Youth Innovation Fund (Grant: 3502Z20206031 to L.L). The SRA accession number for RNA-seq data reported in this paper is: PRJNA783757 (SRR17042317- SRR17042322).įunding: This work was supported by the National Natural Science Foundation of China (Grant: 81925010, 91849205, U190529202 to J.Z. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All data generated or analyzed during this study are included in this published article (and its supplementary information files). Received: ApAccepted: FebruPublished: March 16, 2023Ĭopyright: © 2023 Leng et al. PLoS Biol 21(3):Īcademic Editor: Joseph Castellano, Icahn School of Medicine at Mount Sinai, UNITED STATES (2023) Hypothalamic Menin regulates systemic aging and cognitive decline. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.Ĭitation: Leng L, Yuan Z, Su X, Chen Z, Yang S, Chen M, et al. 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. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. 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. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death.
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