Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Center for Cardiovascular Research and Alternative Medicine,, University of Wyoming College of Health Sciences, Laramie, WY, USA.
Adv Exp Med Biol. 2019;1193:237-253. doi: 10.1007/978-981-13-6260-6_15.
Aging is a complex irreversible biological process associated with increased prevalence of chronic disease and high healthcare burden. Several theories have been proposed for the biology of aging including free radical accumulation, DNA damage, apoptosis, telomere shortening, autophagy failure, and disturbed autonomic response. Aging is also closely associated with progressive deterioration of cardiovascular and neurological functions. Linkage, genome-wide association (GWAS), and next-generation sequencing analysis have confirmed a number of susceptibility loci for aging, in particular, Alzheimer's disease. Recent evidence from our group and others also revealed a tie between genetic mutation of mitochondrial aldehyde dehydrogenase (ALDH2) and life span as well as cardiovascular aging. ALDH2 represents the single most gene with the greatest number of human genetic polymorphism and is deemed an important enzyme for detoxification of reactive aldehydes. Here, we will briefly review the tie between ALDH2 and cardiovascular aging process. While recent work on ALDH2 research has broadened the pathogenic mechanisms of ALDH2 mutation or deficiency, therapeutic potential targeting ALDH2 in the elderly still remains debatable.
衰老是一个复杂的不可逆的生物学过程,与慢性病的高发和高医疗负担有关。几种理论被提出用于解释衰老的生物学机制,包括自由基积累、DNA 损伤、细胞凋亡、端粒缩短、自噬失败和自主神经反应紊乱。衰老是与心血管和神经系统功能的逐渐恶化密切相关的。连锁、全基因组关联 (GWAS) 和下一代测序分析已经证实了许多与衰老相关的易感基因座,特别是阿尔茨海默病。我们小组和其他小组的最近的证据也揭示了线粒体乙醛脱氢酶 (ALDH2) 的基因突变与寿命以及心血管衰老之间的联系。ALDH2 代表了具有最多人类遗传多态性的单个基因,被认为是一种重要的酶,用于解毒反应性醛。在这里,我们将简要回顾 ALDH2 与心血管衰老过程之间的联系。虽然最近关于 ALDH2 研究的工作拓宽了 ALDH2 突变或缺乏的致病机制,但针对老年人的 ALDH2 的治疗潜力仍然存在争议。