心肌细胞衰老与线粒体更新

Myocyte aging and mitochondrial turnover.

作者信息

Terman Alexei, Brunk Ulf T

机构信息

Division of Pathology II, Faculty of Health Sciences, Linköping University, SE-58185 Linkoping, Sweden.

出版信息

Exp Gerontol. 2004 May;39(5):701-5. doi: 10.1016/j.exger.2004.01.005.

DOI:10.1016/j.exger.2004.01.005

PMID:15130664

Abstract

Cardiac myocytes, skeletal muscle fibers, and other long-lived postmitotic cells show dramatic age-related alterations that mainly affect mitochondria and the lysosomal compartment. Mitochondria are primary sites of reactive oxygen species formation that causes progressive damage to mitochondrial DNA and proteins in parallel to intralysosomal lipofuscin accumulation. There is amassing evidence that several various mechanisms may contribute to age-related accumulation of damaged mitochondria following initial oxidative injury. Such mechanisms may include clonal expansion of defective mitochondria, decreased propensity of altered mitochondria to become autophagocytosed (due to mitochondrial enlargement or decreased membrane damage associated with weakened respiration), suppressed autophagy because of heavy lipofuscin loading of lysosomes, and decreased efficiency of Lon protease.

摘要

心肌细胞、骨骼肌纤维和其他长寿命的终末分化细胞表现出与年龄相关的显著变化，这些变化主要影响线粒体和溶酶体区室。线粒体是活性氧形成的主要场所，活性氧会导致线粒体DNA和蛋白质的渐进性损伤，同时伴随着溶酶体内脂褐素的积累。有大量证据表明，在最初的氧化损伤后，多种不同机制可能导致受损线粒体与年龄相关的积累。这些机制可能包括缺陷线粒体的克隆扩增、改变的线粒体被自噬吞噬的倾向降低（由于线粒体增大或与呼吸减弱相关的膜损伤减少）、由于溶酶体大量负载脂褐素导致自噬受到抑制，以及Lon蛋白酶的效率降低。