Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring.
Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring.
复制标题
DOI：
10.18632/aging.100861
复制
发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Franceschi C
中科院分区：
文献类型：
--
作者：
Horvath S;Pirazzini C;Bacalini MG;Gentilini D;Di Blasio AM;Delledonne M;Mari D;Arosio B;Monti D;Passarino G;De Rango F;D'Aquila P;Giuliani C;Marasco E;Collino S;Descombes P;Garagnani P;Franceschi C
鉴于老龄化人口的急剧增加，了解健康老龄化和长寿的遗传和分子决定因素非常重要。半超级百岁老人（年龄在105-109岁之间的人）可以说是人类成功衰老的黄金标准，因为他们设法避免或推迟了与年龄有关的主要疾病的发生。相对而言，很少有研究关注人类极端长寿的表观遗传决定因素。在这里，我们根据一种被称为“表观遗传时钟”的衰老表观遗传生物标志物，测试具有极端长寿的家族在表观遗传上是否与对照组不同。我们分析了82名半超级百岁老人（平均年龄：105.6±1.6岁）、63名半超级百岁老人的后代（平均年龄：71.8±7.8岁）和47名年龄匹配的对照组（平均年龄：69.8±7.2岁）的外周血单个核细胞（PBMCs）的DNA甲基化水平。研究表明，半超级百岁老人的后代表观遗传年龄低于年龄匹配的对照组（年龄差异=5.1岁，p=0.00043），百岁老人比实际年龄预期的要年轻（8.6岁）。相比之下，在估计的血细胞计数（如naïve或耗尽的细胞毒性T细胞或辅助T细胞）方面没有观察到显著差异。未来的研究需要在不同的人群中复制这些发现，并将其扩展到其他组织。总的来说，我们的研究结果表明，表观遗传过程可能在极端长寿和健康的人类衰老中发挥作用。
Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as “epigenetic clock”. We analyze the DNA methylation levels of peripheral blood mononuclear cells (PBMCs) from Italian families constituted of 82 semi-supercentenarians (mean age: 105.6 ± 1.6 years), 63 semi-supercentenarians' offspring (mean age: 71.8 ± 7.8 years), and 47 age-matched controls (mean age: 69.8 ± 7.2 years). We demonstrate that the offspring of semi-supercentenarians have a lower epigenetic age than age-matched controls (age difference=5.1 years, p=0.00043) and that centenarians are younger (8.6 years) than expected based on their chronological age. By contrast, no significant difference could be observed for estimated blood cell counts (such as naïve or exhausted cytotoxic T cells or helper T cells). Future studies will be needed to replicate these findings in different populations and to extend them to other tissues. Overall, our results suggest that epigenetic processes might play a role in extreme longevity and healthy human ageing.