Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Autophagy. 2023 Mar;19(3):957-965. doi: 10.1080/15548627.2022.2111852. Epub 2022 Aug 21.
Macroautophagy/autophagy is necessary for lifespan extension in multiple model organisms and autophagy dysfunction impacts age-related phenotypes and diseases. Introduction of an F121A mutation into the essential autophagy protein BECN1 constitutively increases basal autophagy in young mice and reduces cardiac and renal age-related changes in longer lived mutant mice. However, both autophagic and lysosomal activities decline with age. Thus, whether autophagic flux is maintained during aging and whether it is enhanced in mice is unknown. Here, we demonstrate that old wild-type mice maintained functional autophagic flux in heart, kidney and skeletal muscle but not liver, and old mice had increased autophagic flux in those same organs compared to wild type. In parallel, mice were not protected against age-associated hepatic phenotypes but demonstrated reduced skeletal muscle fiber atrophy. These findings identify an organ-specific role for the ability of autophagy to impact organ aging phenotypes.
自噬是多种模式生物延长寿命所必需的，自噬功能障碍会影响与年龄相关的表型和疾病。在必需的自噬蛋白 BECN1 中引入 F121A 突变，可在年轻小鼠中持续增加基础自噬，并减少长寿突变小鼠的心脏和肾脏与年龄相关的变化。然而，随着年龄的增长，自噬和溶酶体的活性都会下降。因此，自噬流是否在衰老过程中得到维持，以及在 突变小鼠中是否得到增强尚不清楚。在这里，我们证明了衰老的野生型小鼠在心脏、肾脏和骨骼肌中保持了功能正常的自噬流，但在肝脏中没有，而与野生型相比，衰老的 小鼠在这些相同的器官中具有增加的自噬流。与此平行， 小鼠不能防止与年龄相关的肝脏表型，但表现出减少的骨骼肌纤维萎缩。这些发现确定了自噬影响器官衰老表型的一种器官特异性作用。
