Age-Related Disease Association of Endogenous γ-H2AX Foci in Mononuclear Cells Derived from Leukapheresis

被引：25

作者：

Schurman, Shepherd H. ^{[1
]}

Dunn, Christopher A. ^{[1
]}

Greaves, Rebecca ^{[1
]}

Yu, Binbing ^{[2
]}

Ferrucci, Luigi ^{[3
]}

Croteau, Deborah L. ^{[1
]}

Seidman, Michael M. ^{[1
]}

Bohr, Vilhelm A. ^{[1
]}

机构：

[1] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA

[2] NIA, Lab Epidemiol Demog & Biometry, NIH, Baltimore, MD 21224 USA

[3] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA

来源：

PLOS ONE | 2012年 / 7卷 / 09期

基金：

美国国家卫生研究院;

关键词：

DOUBLE-STRAND BREAKS; OBSTRUCTIVE SLEEP-APNEA; OXIDATIVE DNA-DAMAGE; MOLECULAR MARKER; HISTONE H2AX; VITAMIN-D; REPAIR; HYPERTENSION; LYMPHOCYTES; CANCER;

D O I：

10.1371/journal.pone.0045728

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The phosphorylated form of histone H2AX (gamma-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, gamma-H2AX foci increased in a linear fashion with regards to age, peaking at similar to 57 years. The relationship between the frequency of gamma-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 gamma-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 gamma-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. gamma-H2AX may be a biomarker for human morbidity in age-related diseases.

引用

页数：8

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