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

作者:Schurman Shepherd H; Dunn Christopher A; Greaves Rebecca; Yu Binbing; Ferrucci Luigi; Croteau Deborah L; Seidman Michael M; Bohr Vilhelm A*
来源:PLos One, 2012, 7(9): e45728.
DOI:10.1371/journal.pone.0045728

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.

  • 出版日期2012-9-21