美国圣路易斯华盛顿大学医学院Shin-ichiro Imai研究组的一项最新发现揭示，包含eNAMPT的胞外囊泡能够延缓衰老并延长小鼠的寿命。2019年8月出版的《细胞—代谢》发表了这项成果。

研究人员发现在小鼠和人类中，细胞外烟酰胺磷酸核糖转移酶（eNAMPT）的循环水平随着年龄的增长而显著下降。在老年小鼠中，通过脂肪组织特异性过表达NAMPT对eNAMPT循环水平的增加，可以提升多种组织中的NAD+水平，进而增强其功能并延长雌性小鼠的健康寿命。有趣的是，eNAMPT储存在胞外囊泡（EV）中从而在小鼠和人类中进行全身循环。包含eNAMPT的EV进入细胞，促进NAD+的生物合成。补充从幼鼠分离的含eNAMPT的EV可以显著改善踏转轮活动，并延长老年小鼠的寿命。他们的发现揭示了一种新的EV介导的eNAMPT传递机制，其可促进全身性NAD+的生物合成并抑制衰老，为人类抗衰老干预提供了一条潜在的途径。

据了解，衰老是组织功能受损和慢性疾病的重要危险因素。在许多物种中，与年龄相关的全身NAD+可用性下降在调节衰老过程中起着关键作用。

附：英文原文

Title: Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice

Author: Mitsukuni Yoshida, Akiko Satoh, Jonathan B. Lin, Kathryn F. Mills, Yo Sasaki, Nicholas Rensing, Michael Wong, Rajendra S. Apte, Shin-ichiro Imai

Issue&Volume:  Volume 30 Issue 2

Abstract: Aging is a significant risk factor for impaired tissue functions and chronic diseases. Age-associated decline in systemic NAD + availability plays a critical role in regulating the aging process across many species. Here, we show that the circulating levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) significantly decline with age in mice and humans. Increasing circulating eNAMPT levels in aged mice by adipose-tissue-specific overexpression of NAMPT increases NAD + levels in multiple tissues, thereby enhancing their functions and extending healthspan in female mice. Interestingly, eNAMPT is carried in extracellular vesicles (EVs) through systemic circulation in mice and humans. EV-contained eNAMPT is internalized into cells and enhances NAD + biosynthesis. Supplementing eNAMPT-containing EVs isolated from young mice significantly improves wheel-running activity and extends lifespan in aged mice. Our findings have revealed a novel EV-mediated delivery mechanism for eNAMPT, which promotes systemic NAD + biosynthesis and counteracts aging, suggesting a potential avenue for anti-aging intervention in humans.

DOI: https://doi.org/10.1016/j.cmet.2019.05.015

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30255-4