Shigenaga M K, Hagen T M, Ames B N
Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10771-8. doi: 10.1073/pnas.91.23.10771.
We argue for the critical role of oxidative damage in causing the mitochondrial dysfunction of aging. Oxidants generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age. Several mitochondrial functions decline with age. The contributing factors include the intrinsic rate of proton leakage across the inner mitochondrial membrane (a correlate of oxidant formation), decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane. Acetyl-L-carnitine, a high-energy mitochondrial substrate, appears to reverse many age-associated deficits in cellular function, in part by increasing cellular ATP production. Such evidence supports the suggestion that age-associated accumulation of mitochondrial deficits due to oxidative damage is likely to be a major contributor to cellular, tissue, and organismal aging.
我们认为氧化损伤在导致衰老相关的线粒体功能障碍中起着关键作用。线粒体产生的氧化剂似乎是随年龄积累的氧化损伤的主要来源。随着年龄的增长，几种线粒体功能会下降。促成因素包括质子跨线粒体内膜泄漏的内在速率（与氧化剂形成相关）、膜流动性降低以及心磷脂水平和功能下降，心磷脂支持线粒体内膜许多蛋白质的功能。乙酰-L-肉碱是一种高能线粒体底物，似乎可以逆转许多与年龄相关的细胞功能缺陷，部分原因是增加细胞ATP的产生。这些证据支持了这样的观点，即由于氧化损伤导致的与年龄相关的线粒体缺陷积累很可能是细胞、组织和机体衰老的主要促成因素。
