小柯机器人

美国华盛顿大学医学院Shin-ichiro Imai团队近期取得重要工作进展，他们研究发现，DMH^Ppp1r17神经元通过下丘脑-脂肪组织间通讯调节小鼠衰老和寿命。相关研究成果2024年1月8日在线发表于《细胞—代谢》杂志上。

据介绍，近期研究表明，下丘脑是哺乳动物衰老的控制中心，通过组织间通讯抵消与衰老相关的生理衰退。

研究人员已经在下丘脑背内侧（DMH）中确定了一个关键的神经元亚群，其以Pp1r17表达为标志（DMH^Ppp1r17神经元），调节小鼠的衰老和寿命。DMH^Ppp1r17神经元通过交感神经刺激调节身体活动和WAT功能，包括细胞外烟酰胺磷酸核糖转移酶（eNAMPT）的分泌。

在DMH^Ppp1r17神经元中，由cGMP依赖性蛋白激酶G（PKG；Prkg1）调节的Ppp1r117的磷酸化和随后的核质易位影响调节突触功能的基因表达，导致突触传递功能障碍和WAT功能受损。DMH特异性Prkg1敲低（抑制年龄相关的Ppp1r17易位）和DMH^Ppp1r117神经元的化学遗传学激活都能显著改善WAT中年龄相关的功能障碍，增加体力活动，延长寿命。

因此，这些发现清楚地证明了下丘脑和WAT之间组织间通信在哺乳动物衰老和寿命控制中的重要性。

附：英文原文

Title: DMHPpp1r17 neurons regulate aging and lifespan in mice through hypothalamic-adipose inter-tissue communication

Author: Kyohei Tokizane, Cynthia S. Brace, Shin-ichiro Imai

Issue&Volume: 2024-01-08

Abstract: Recent studies have shown that the hypothalamus functions as a control center of aging in mammals that counteracts age-associated physiological decline through inter-tissue communications. We have identified a key neuronal subpopulation in the dorsomedial hypothalamus (DMH), marked by Ppp1r17 expression (DMHPpp1r17 neurons), that regulates aging and longevity in mice. DMHPpp1r17 neurons regulate physical activity and WAT function, including the secretion of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), through sympathetic nervous stimulation. Within DMHPpp1r17 neurons, the phosphorylation and subsequent nuclear-cytoplasmic translocation of Ppp1r17, regulated by cGMP-dependent protein kinase G (PKG; Prkg1), affect gene expression regulating synaptic function, causing synaptic transmission dysfunction and impaired WAT function. Both DMH-specific Prkg1 knockdown, which suppresses age-associated Ppp1r17 translocation, and the chemogenetic activation of DMHPpp1r17 neurons significantly ameliorate age-associated dysfunction in WAT, increase physical activity, and extend lifespan. Thus, these findings clearly demonstrate the importance of the inter-tissue communication between the hypothalamus and WAT in mammalian aging and longevity control.

DOI: 10.1016/j.cmet.2023.12.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00462-X

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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