Life expectancy continues to increase in the high-income world due to advances in medical care; however, quality of life declines with increasing age due to normal aging processes. Current research suggests that various aspects of aging are genetically modulated and thus may be slowed via genetic modification. Here, we show evidence for epigenetic modulation of the aging process in the brain from over 1800 individuals as part of the Framingham Heart Study. We investigated the methylation of genes in the protocadherin (PCDH) clusters, including the alpha (PCHDA), beta (PCDHB), and gamma (PCDHG) clusters. Reduced PCDHG, elevated PCDHA, and elevated PCDHB methylation levels were associated with substantial reductions in the rate of decline of regional white matter volume as well as certain cognitive skills, independent of overall accelerated or retarded aging as estimated by a DNA clock. These results are likely due to the different effects of the expression of genes in the alpha, beta, and gamma PCHD clusters and suggest that experience-based aging processes related to a decline in regional brain volume and select cognitive skills may be slowed via targeted epigenetic modifications.

中文翻译：

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原钙粘蛋白表观遗传学对衰老相关大脑健康的复杂调节

由于医疗保健的进步，高收入国家的预期寿命持续增长；然而，由于正常的衰老过程，生活质量随着年龄的增长而下降。目前的研究表明，衰老的各个方面都受到基因调节，因此可以通过基因改造来减缓衰老。在这里，作为弗雷明汉心脏研究的一部分，我们展示了来自 1800 多名个体的大脑衰老过程表观遗传调节的证据。我们研究了原钙粘蛋白 (PCDH) 簇中基因的甲基化，包括 α ( PCHDA )、β ( PCDHB ) 和 γ ( PCDHG ) 簇。PCDHG降低、PCDHA升高和PCDHB甲基化水平升高与区域白质体积下降率以及某些认知技能的大幅降低相关，与 DNA 时钟估计的总体加速或延缓衰老无关。这些结果可能是由于α、β和γ PCHD簇中基因表达的不同影响所致，并表明与区域脑容量和选择认知技能下降相关的基于经验的衰老过程可以通过有针对性的表观遗传来减缓修改。