Department of Medicine, Division of Geriatrics, UCLA, Los Angeles, CA 90095, USA.
Mech Ageing Dev. 2010 Jul-Aug;131(7-8):527-35. doi: 10.1016/j.mad.2010.06.002. Epub 2010 Jun 8.
Aging of the American society is leading to a growing need for disease-modifying interventions to treat age-related diseases and enhance healthspan. Mitochondria and mitochondrially generated reactive oxygen species appear to play a central role in these processes and are a likely target for interventions. Conventional, untargeted antioxidants have not demonstrated a clear benefit in human studies. As a result, approaches have been developed to target antioxidants specifically to mitochondria. Studies have employed a wide array of targeted molecules including antioxidant enzymes such as catalase, peroxiredoxin, superoxide dismutases and small molecular compounds which recapitulate the antioxidant activities of these enzymes. Lifespan and healthspan effects differ between interventions suggesting varied roles for specific mitochondrial reactive oxygen species and their impact on usual aging. Consistent findings in myocardial protection across various interventions support a focus on the impact of cardiac aging on healthspan. The advancement of mitochondrially targeted small-molecule antioxidants suggests the prospect of swift translation to human use.
美国社会的老龄化导致人们对疾病修饰干预的需求不断增长，以治疗与年龄相关的疾病和延长健康寿命。线粒体和线粒体产生的活性氧似乎在这些过程中起着核心作用，是干预的一个可能目标。传统的、非靶向的抗氧化剂在人类研究中没有表现出明显的益处。因此，已经开发出了针对线粒体的靶向抗氧化剂的方法。研究采用了广泛的靶向分子，包括抗氧化酶，如过氧化氢酶、过氧化物酶、超氧化物歧化酶和小分子化合物，这些分子再现了这些酶的抗氧化活性。干预措施的寿命和健康寿命效应不同，这表明特定的线粒体活性氧及其对一般衰老的影响有不同的作用。各种干预措施在心肌保护方面的一致发现支持关注心脏衰老对健康寿命的影响。针对线粒体的小分子抗氧化剂的进展表明，有望迅速转化为人类使用。
