Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
PLoS One. 2012;7(9):e45728. doi: 10.1371/journal.pone.0045728. Epub 2012 Sep 21.
The phosphorylated form of histone H2AX (γ-H2AX) forms immunohistochemically detectable foci at DNA double strand breaks. In peripheral blood mononuclear cells (PBMCs) derived from leukapheresis from patients enrolled in the Baltimore Longitudinal Study of Aging, γ-H2AX foci increased in a linear fashion with regards to age, peaking at ~57 years. The relationship between the frequency of γ-H2AX foci and age-related pathologies was assessed. We found a statistically significant (p = 0.023) 50% increase in foci in PBMCs derived from patients with a known history of vitamin D deficiency. In addition, there were trends toward increased γ-H2AX foci in patients with cataracts (34% increase, p<0.10) and in sleep apnea patients (44%, p<0.10). Among patients ≥57 y/o, we found a significant (p = 0.037) 36% increase in the number of γ-H2AX foci/cell for patients with hypertension compared to non-hypertensive patients. Our results support a role for increased DNA damage in the morbidity of age-related diseases. γ -H2AX may be a biomarker for human morbidity in age-related diseases.
组蛋白 H2AX 的磷酸化形式（γ-H2AX）在 DNA 双链断裂处形成免疫组织化学上可检测的焦点。在巴尔的摩老龄化纵向研究中从白细胞分离术获得的外周血单核细胞 (PBMC) 中，γ-H2AX 焦点随着年龄的增长呈线性增加，在~57 岁时达到峰值。评估了 γ-H2AX 焦点与与年龄相关的病理学之间的关系。我们发现，在已知维生素 D 缺乏病史的患者的 PBMC 中，焦点的频率呈统计学显著（p = 0.023）增加了 50%。此外，在白内障患者（增加 34%，p<0.10）和睡眠呼吸暂停患者（增加 44%，p<0.10）中，γ-H2AX 焦点也有增加的趋势。在≥57 岁的患者中，我们发现与非高血压患者相比，高血压患者的 γ-H2AX 焦点/细胞数增加了 36%（p = 0.037）。我们的研究结果支持 DNA 损伤增加在与年龄相关的疾病发病机制中的作用。γ-H2AX 可能是与年龄相关疾病患者发病的生物标志物。
