Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Healthy Longevity, National University Health System, Singapore.
Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Healthy Longevity, National University Health System, Singapore.
Alcohol. 2023 Mar;107:91-96. doi: 10.1016/j.alcohol.2022.07.009. Epub 2022 Aug 18.
While the detrimental effects of binge drinking are well recognized, low-to-moderate alcohol consumption may be beneficial to health, although the underlying mechanism(s) remains elusive. In this opinion article, we will examine the effects of low dose alcohol consumption from the perspective of epigenetic modulation. Biochemically, alcohol is metabolized into acetate and subsequently to acetyl-coA, which can modulate histone acetylation levels. While elevated levels of acetyl-CoA are detrimental for longevity, we argue that diminished acetyl-CoA also negatively affects fatty acid biosynthesis and histone acetylation, which play a critical role in gene expression and, ultimately, health span. Since mitochondrial function and glucose metabolism, which provide the main source of nucleocytoplasmic acetyl-CoA, are compromised with age, alcohol-derived acetate could be an alternative source of acetyl-CoA to compensate. Hence, the health benefits of low ethanol consumption may be more pronounced after midlife, since mitochondrial function and/or glucose metabolism are diminished in this phase of the life course. Indeed, various clinical alcohol consumption studies concur with this notion, and have shown that a low dose of regular alcohol intake after midlife brings about various health and survival benefits. The requirement for regular alcohol intake may also reflect the transient nature of ethanol-induced histone acetylation. Conversely, ethanol may also stimulate carcinogenesis by inhibiting DNA methylation, as it was shown to reduce various pathways leading to DNA and histone methylation. However, unlike acetylation, where ethanol directly increases the substrate for acetylation, this effect was only observed in the high alcohol exposure cohort. While alcohol-derived acetate may be beneficial for health after midlife, various detrimental effects of alcohol consumption remain, and hence, we do not advocate excessive drinking to increase acetate. This opinion article establishes a possible role of ethanol-derived acetate in achieving homeostasis and sustaining an organism's health span.
虽然 binge drinking（狂饮）的有害影响已得到广泛认可，但低至中度的酒精摄入可能对健康有益，尽管其潜在机制仍难以捉摸。在这篇观点文章中，我们将从表观遗传调控的角度探讨低剂量酒精摄入的影响。从生化角度来看，酒精代谢为乙酸盐，然后转化为乙酰辅酶 A，后者可以调节组蛋白乙酰化水平。虽然乙酰辅酶 A 水平升高对长寿有害，但我们认为，乙酰辅酶 A 水平降低也会对脂肪酸生物合成和组蛋白乙酰化产生负面影响，而这两者在基因表达中起着关键作用，并最终影响健康寿命。由于线粒体功能和葡萄糖代谢为核质提供了主要的乙酰辅酶 A 来源，随着年龄的增长，它们会受到损害，因此，酒精衍生的乙酸盐可能是乙酰辅酶 A 的替代来源来进行补偿。因此，低乙醇消耗的健康益处可能在中年以后更为明显，因为在此生命阶段，线粒体功能和/或葡萄糖代谢会减弱。事实上，各种临床酒精摄入研究都证实了这一观点，并表明中年以后定期摄入低剂量的酒精会带来各种健康和生存益处。对定期饮酒的需求也可能反映了乙醇诱导的组蛋白乙酰化的短暂性质。相反，乙醇也可能通过抑制 DNA 甲基化来刺激致癌作用，因为它被证明会减少导致 DNA 和组蛋白甲基化的各种途径。然而，与直接增加乙酰化底物的乙酰化不同，乙醇仅在高酒精暴露组中观察到这种抑制 DNA 甲基化的作用。虽然酒精衍生的乙酸盐可能对中年以后的健康有益，但酒精摄入仍存在各种有害影响，因此，我们不提倡通过过量饮酒来增加乙酸盐。这篇观点文章确立了乙醇衍生的乙酸盐在实现体内平衡和维持生物体健康寿命方面的可能作用。
