Gruber Jan, Halliwell Barry
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Science Division, Yale-NUS College, Singapore.
Essays Biochem. 2017 Jul 11;61(3):389-399. doi: 10.1042/EBC20160091. Print 2017 Jul 15.
Dramatic increases in human lifespan and declining population growth are monumental achievements but these same achievements have also led to many societies today ageing at a faster rate than ever before. Extending healthy lifespan (healthspan) is a key translational challenge in this context. Disease-centric approaches to manage population ageing risk are adding years to life without adding health to these years. The growing consensus that ageing is driven by a limited number of interconnected processes suggests an alternative approach. Instead of viewing each age-dependent disease as the result of an independent chain of events, this approach recognizes that most age-dependent diseases depend on and are driven by a limited set of ageing processes. While the relative importance of each of these processes and the best intervention strategies targeting them are subjects of debate, there is increasing interest in providing preventative intervention options to healthy individuals even before overt age-dependent diseases manifest. Elevated oxidative damage is involved in the pathophysiology of most age-dependent diseases and markers of oxidative damage often increase with age in many organisms. However, correlation is not causation and, sadly, many intervention trials of supposed antioxidants have failed to extend healthspan and to prevent diseases. This does not, however, mean that reactive species (RS) and redox signalling are unimportant. Ultimately, the most effective antioxidants may not turn out to be the best geroprotective drugs, but effective geroprotective interventions might well turn out to also have excellent, if probably indirect, antioxidant efficacy.
人类寿命的显著延长和人口增长的下降是巨大的成就，但同样这些成就也导致当今许多社会老龄化的速度比以往任何时候都要快。在这种背景下，延长健康寿命（健康跨度）是一个关键的转化医学挑战。以疾病为中心应对人口老龄化风险的方法在增加寿命的同时，并没有让这些年的生活更健康。越来越多的共识认为，衰老由有限数量的相互关联的过程驱动，这提示了一种替代方法。这种方法不是将每种与年龄相关的疾病视为独立事件链的结果，而是认识到大多数与年龄相关的疾病依赖于并由一组有限的衰老过程驱动。虽然这些过程中每个过程的相对重要性以及针对它们的最佳干预策略仍存在争议，但人们越来越有兴趣在明显的与年龄相关的疾病出现之前，就为健康个体提供预防性干预选择。氧化损伤增加参与了大多数与年龄相关疾病的病理生理学过程，并且在许多生物体中，氧化损伤的标志物通常会随着年龄的增长而增加。然而，相关性并不等同于因果关系，遗憾的是，许多所谓抗氧化剂的干预试验未能延长健康跨度和预防疾病。然而，这并不意味着活性氧（RS）和氧化还原信号不重要。最终，最有效的抗氧化剂可能并非最佳的老年保护药物，但有效的老年保护干预措施很可能也具有出色的抗氧化功效，即便可能是间接的。
