Association of Epigenetic Age and p16INK4a With Markers of T-Cell Composition in a Healthy Cohort
Association of Epigenetic Age and p16INK4a With Markers of T-Cell Composition in a Healthy Cohort
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DOI：
10.1093/gerona/glaa108
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发表时间：
2020-12-01
影响因子：
5.1
通讯作者：
Kiecolt-Glaser, Janice K.
中科院分区：
文献类型：
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作者：
Burd, Christin E.;Peng, Juan;Kiecolt-Glaser, Janice K.
外周血T淋巴细胞(PBTL)中老化生物标志物的测量如何受到细胞组成的影响尚不清楚。在这里，我们采集了117对年龄在21岁到72岁之间的健康夫妇的外周血和分离的CD3(+)PBTL。分析每个样本的Horvath表观遗传时钟(DNaM)、p16(INK4a)表达、巨细胞病毒(CMV)血清阳性和74个PBTL亚型、分化、免疫检查点和细胞因子产生的mRNA标记物。个体衰老生物标志物(dNaM或p16(INK4a))和PBTL mRNAs之间的相关性按年龄、性别和夫妇进行了校正。DNaM测定与CMV血清阳性以及PBTL mRNAs相关，这些mRNAs指示效应器功能(CD8A、EBES、Tbx21、GZMB)、低增殖能力(KLRG1、CD57)、分化(CD45RO、CD45RA)和免疫检查点(PDCD1、TIGIT、LAG3、CD160、CD244)。相反，只有CD28、CD244和p14(ARF)三个PBTL mRNAs与p16(INK4a)显著相关。在流式细胞术分析中，p16(INK4a)的表达与免疫衰弱的PBTL亚群的相关性也弱于dNaM。这些数据表明，PBTL的组成对dNaM的影响比p16(INK4a)更大，并将加速的表观遗传老化与免疫衰老表型联系起来。
How the measurement of aging biomarkers in peripheral blood T-lymphocytes (PBTLs) is influenced by cell composition is unclear. Here, we collected peripheral blood and isolated CD3(+) PBTLs from 117 healthy couples between the ages of 21 and 72. Each sample was profiled for Horvath epigenetic clock (DNAm), p16(INK4a) expression, cytomegalovirus (CMV) seropositivity and 74 mRNA markers of PBTL subtype, differentiation, immune checkpoints, and cytokine production. Correlations between individual aging biomarkers (DNAm or p16(INK4a)) and PBTL mRNAs were corrected for chronological age, sex, and couple. DNAm measurements correlated with CMV seropositivity as well as PBTL mRNAs indicative of effector function (CD8A, EOMES, TBX21, GZMB), poor proliferative capacity (KLRG1, CD57), differentiation (CD45RO, CD45RA), and immune checkpoints (PDCD1, TIGIT, LAG3, CD160, CD244). In contrast, only three PBTL mRNAs, CD28, CD244, and p14(ARF), showed a significant association with p16(INK4a). p16(INK4a) expression also showed a weaker association with immunosenescent PBTL subsets than DNAm in flow cytometry analyses. These data suggest that PBTL composition has a greater influence on DNAm than p16(INK4a) and link accelerated epigenetic aging to immunosenescent phenotypes.