School of Life Sciences, Chongqing University, Chongqing, China.
School of Life Sciences, Chongqing University, Chongqing, China.
J Biol Chem. 2022 Jul;298(7):102118. doi: 10.1016/j.jbc.2022.102118. Epub 2022 Jun 9.
Sphingolipids are a class of bioactive complex lipids that have been closely associated with aging and aging-related diseases. However, the mechanism through which sphingolipids control aging has long been a mystery. Emerging studies reveal that sphingolipids exert tight control over lysosomal homeostasis and function, as evidenced by sphingolipid-related diseases, including but not limited to lysosomal storage disorders. These diseases are defined by primary lysosomal defects and a few secondary defects such as mitochondrial dysfunction. Intriguingly, recent research indicates that the majority of these defects are also associated with aging, implying that sphingolipid-related diseases and aging may share common mechanisms. We propose that the lysosome is a pivotal hub for sphingolipid-mediated aging regulation. This review discusses the critical roles of sphingolipid metabolism in regulating various lysosomal functions, with an emphasis on how such regulation may contribute to aging and aging-related diseases.
鞘脂类是一类具有生物活性的复杂脂质，与衰老和衰老相关的疾病密切相关。然而，鞘脂类控制衰老的机制长期以来一直是个谜。新出现的研究表明，鞘脂类对溶酶体的稳态和功能有严格的控制作用，这一点可以从鞘脂类相关疾病中得到证明，包括但不限于溶酶体贮积症。这些疾病的特征是主要的溶酶体缺陷和一些次要的缺陷，如线粒体功能障碍。有趣的是，最近的研究表明，大多数这些缺陷也与衰老有关，这意味着鞘脂类相关疾病和衰老可能有共同的机制。我们提出溶酶体是鞘脂类介导的衰老调节的关键枢纽。这篇综述讨论了鞘脂代谢在调节各种溶酶体功能中的关键作用，重点讨论了这种调节如何有助于衰老和衰老相关的疾病。
