Accelerated epigenetic age and cognitive decline among urban-dwelling adults
Accelerated epigenetic age and cognitive decline among urban-dwelling adults
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DOI：
10.1212/wnl.0000000000008756
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发表时间：
2020-02-11
期刊：
影响因子：
9.9
通讯作者：
Zonderman, Alan B.
中科院分区：
文献类型：
--
作者：
Beydoun, May A.;Shaked, Danielle;Zonderman, Alan B.
目的表观遗传修饰与衰老密切相关，但其与认知的关系仍然模棱两可。鉴于表观遗传衰老中已知的性别差异，我们探讨了基于 3 个 DNA 甲基化 (DNAm) 的表观遗传年龄加速 (EAA) 测量与中年城市成年人认知表现的基线和纵向变化的性别特异性关联。方法我们使用来自整个生命周期多样性社区健康老龄化研究中的一组参与者的探索性数据和完整的 DNA 样本，其基线年龄 > 50.0 岁 (2004-2009) 来估计3种DNAm EAA测量：（1）通用EAA（AgeAccel）； （2）内在EAA（IEAA）； (3) 外在 EAA (EEAA)。认知表现是在基线访问（2004-2009）和第一次随访（2009-2013）时测量的，11个测试分数涵盖整体心理状态和特定领域，如学习/记忆、注意力、视觉空间、精神运动速度、语言/言语和执行功能。我们对协变量和多重测试进行了一系列混合效应回归模型的调整（n = 147-156，与 51% 男性相似，k = 1.7-1.9 个观察值/参与者，平均随访时间与 4.7 年相似）。结果 EEAA（生物年龄和免疫衰老的衡量标准）与男性在视觉记忆/视觉建构能力测试中更大的认知能力下降一致相关（本顿视觉保留测试：gamma） (11) = 0.0512 0.0176，p = 0.004) 和注意力/处理速度（轨迹制作测试，A 部分：gamma (11) = 0.219 +/- 0.080，p = 0.007）。 AgeAccel 和 IEAA 与该样本中的认知变化无关。结论 EEAA 捕获免疫系统细胞衰老与男性注意力和视觉记忆领域的更快下降有关。需要更大规模的纵向研究来复制我们的发现。
ObjectivesEpigenetic modifications are closely linked with aging, but their relationship with cognition remains equivocal. Given known sex differences in epigenetic aging, we explored sex-specific associations of 3 DNA methylation (DNAm)-based measures of epigenetic age acceleration (EAA) with baseline and longitudinal change in cognitive performance among middle-aged urban adults.MethodsWe used exploratory data from a subgroup of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with complete DNA samples and whose baseline ages were >50.0 years (2004-2009) to estimate 3 DNAm EAA measures: (1) universal EAA (AgeAccel); (2) intrinsic EAA (IEAA); and (3) extrinsic EAA (EEAA). Cognitive performance was measured at baseline visit (2004-2009) and first follow-up (2009-2013) with 11 test scores covering global mental status and specific domains such as learning/memory, attention, visuospatial, psychomotor speed, language/verbal, and executive function. A series of mixed-effects regression models were conducted adjusting for covariates and multiple testing (n = 147-156, similar to 51% men, k = 1.7-1.9 observations/participant, mean follow-up time similar to 4.7 years).ResultsEEAA, a measure of both biological age and immunosenescence, was consistently associated with greater cognitive decline among men on tests of visual memory/visuoconstructive ability (Benton Visual Retention Test: gamma (11) = 0.0512 0.0176, p = 0.004) and attention/processing speed (Trail-Making Test, part A: gamma (11) = 0.219 +/- 0.080, p = 0.007). AgeAccel and IEAA were not associated with cognitive change in this sample.ConclusionsEEAA capturing immune system cell aging was associated with faster decline among men in domains of attention and visual memory. Larger longitudinal studies are needed to replicate our findings.