Hagen Tory M, Moreau Régis, Suh Jung H, Visioli Francesco
Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA.
Ann N Y Acad Sci. 2002 Apr;959:491-507. doi: 10.1111/j.1749-6632.2002.tb02119.x.
Mitochondrial decay has been postulated to be a significant underlying part of the aging process. Decline in mitochondrial function may lead to cellular energy deficits, especially in times of greater energy demand, and compromise vital ATP-dependent cellular operations, including detoxification, repair systems, DNA replication, and osmotic balance. Mitochondrial decay may also lead to enhanced oxidant production and thus render the cell more prone to oxidative insult. In particular, the heart may be especially susceptible to mitochondrial dysfunction due to myocardial dependency on beta-oxidation of fatty acids for energy and the postmitotic nature of cardiac myocytes, which would allow for greater accumulation of mitochondrial mutations and deletions. Thus, maintenance of mitochondrial function may be important to maintain overall myocardial function. Herein, we review the major age-related changes that occur to mitochondria in the aging heart and the evidence that two such supplements, acetyl-l-carnitine (ALCAR) and (R)-alpha-lipoic acid, may improve myocardial bioenergetics and lower the increased oxidative stress associated with aging. We and others have shown that feeding old rats ALCAR reverses the age-related decline in carnitine levels and improves mitochondrial beta-oxidation in a number of tissues studied. However, ALCAR supplementation does not appear to reverse the age-related decline in cardiac antioxidant status and thus may not substantially alter indices of oxidative stress. Lipoic acid, a potent thiol antioxidant and mitochondrial metabolite, appears to increase low molecular weight antioxidant status and thereby decreases age-associated oxidative insult. Thus, ALCAR along with lipoic acid may be effective supplemental regimens to maintain myocardial function.
线粒体衰退被认为是衰老过程中一个重要的潜在因素。线粒体功能的下降可能导致细胞能量不足，尤其是在能量需求增加的时候，并损害重要的ATP依赖的细胞活动，包括解毒、修复系统、DNA复制和渗透平衡。线粒体衰退还可能导致氧化剂产生增加，从而使细胞更容易受到氧化损伤。特别是，心脏可能对线粒体功能障碍特别敏感，这是由于心肌依赖脂肪酸的β氧化来获取能量，以及心肌细胞的终末分化性质，这会使线粒体突变和缺失的积累更多。因此，维持线粒体功能对于维持整体心肌功能可能很重要。在此，我们综述了衰老心脏中线粒体发生的与年龄相关的主要变化，以及两种补充剂，乙酰左旋肉碱（ALCAR）和（R）-α-硫辛酸，可能改善心肌生物能量学并降低与衰老相关的氧化应激增加的证据。我们和其他人已经表明，给老年大鼠喂食ALCAR可以逆转与年龄相关的肉碱水平下降，并改善所研究的许多组织中的线粒体β氧化。然而，补充ALCAR似乎并不能逆转与年龄相关的心脏抗氧化状态下降，因此可能不会显著改变氧化应激指标。硫辛酸是一种有效的硫醇抗氧化剂和线粒体代谢物，似乎可以提高低分子量抗氧化剂状态，从而减少与年龄相关的氧化损伤。因此，ALCAR与硫辛酸一起可能是维持心肌功能的有效补充方案。
