title: Age-related disease association of endogenous γ-H2AX foci in mononuclear cells derived from leukapheresis.
abstract: 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.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Shepherd H
authors.initials: SH
authors.lastname: Schurman
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Dunn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Greaves
authors.forename: Binbing
authors.initials: B
authors.lastname: Yu
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Croteau
authors.forename: Michael M
authors.initials: MM
authors.lastname: Seidman
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000375:Aging / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: C468783:H2AX protein, human; D006657:Histones