Lazarus Jessica, Mather Karen A, Thalamuthu Anbupalam, Kwok John B J
Neuroscience Research Australia, Barker Street, Randwick, Sydney, NSW 2031, Australia.
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Epigenomics. 2015;7(8):1339-49. doi: 10.2217/epi.15.80. Epub 2015 Dec 7.
The exceptional longevity phenotype, defined as living beyond the age of 95, results from complex interactions between environmental and genetic factors. Epigenetic mechanisms, such as DNA methylation and histone modifications, mediate the interaction of these factors. This review will provide an overview of animal model studies used to examine age-related epigenetic modifications. Key human studies will be used to illustrate the progress made in the identification of the genetic loci associated with exceptional longevity, including APOE and FOXO3 and genes/loci that are also differentially methylated between long-lived individuals and younger controls. Future studies should focus on elucidating whether identified longevity genetic loci directly influence epigenetic mechanisms, especially on differentially methylated regions associated with longevity.
异常长寿表型定义为活到95岁以上，它是环境因素和遗传因素之间复杂相互作用的结果。表观遗传机制，如DNA甲基化和组蛋白修饰，介导了这些因素之间的相互作用。本综述将概述用于研究与年龄相关的表观遗传修饰的动物模型研究。将引用关键的人体研究来说明在识别与异常长寿相关的基因位点方面所取得的进展，包括载脂蛋白E（APOE）和叉头框O3（FOXO3），以及在长寿个体和年轻对照之间也存在差异甲基化的基因/位点。未来的研究应侧重于阐明已识别的长寿基因位点是否直接影响表观遗传机制，尤其是与长寿相关的差异甲基化区域。
