BECN1F121A mutation increases autophagic flux in aged mice and improves aging phenotypes in an organ-dependent manner.
BECN1F121A mutation increases autophagic flux in aged mice and improves aging phenotypes in an organ-dependent manner.
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BECN1F121A 突变增加了老年小鼠的自噬通量，并以器官依赖性方式改善了衰老表型。
DOI：
10.1080/15548627.2022.2111852
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发表时间：
2023
期刊：
影响因子：
13.3
通讯作者：
Shiloh,MichaelU
中科院分区：
文献类型：
--
作者：
Sebti,Salwa;Zou,Zhongju;Shiloh,MichaelU
巨自噬/自噬对于多种模式生物的寿命延长是必要的，并且自噬功能障碍影响年龄相关的表型和疾病。将F121 A突变引入到必需的自噬蛋白BECN 1中，组成性地增加了年轻小鼠的基础自噬，并减少了长寿Becn 1F 121 A突变小鼠的心脏和肾脏年龄相关变化。然而，自噬和溶酶体活性都随着年龄的增长而下降。因此，自噬通量是否在老化过程中保持，以及它是否在Becn 1F 121 Amice中增强尚不清楚。在这里，我们证明了老年野生型小鼠在心脏，肾脏和骨骼肌中保持功能性自噬通量，而不是肝脏，与野生型相比，oldBecn 1F 121 Amice在这些相同的器官中增加了自噬通量。与此同时，Becn 1F 121 Amice没有保护年龄相关的肝脏表型，但表现出骨骼肌纤维萎缩减少。这些发现确定了自噬影响器官衰老表型的能力的器官特异性作用。
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 livedBecn1F121Amutant mice. However, both autophagic and lysosomal activities decline with age. Thus, whether autophagic flux is maintained during aging and whether it is enhanced inBecn1F121Amice is unknown. Here, we demonstrate that old wild-type mice maintained functional autophagic flux in heart, kidney and skeletal muscle but not liver, and oldBecn1F121Amice had increased autophagic flux in those same organs compared to wild type. In parallel,Becn1F121Amice 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.