Non homologous end joining-mediated DNA break repair is impaired in B lymphocytes of aging mice.

Abstract:

:Aging is an irreversible physiological process characterized by increased risk of diseases, reduced effectiveness of vaccines, and decreased immune responses. One of the most prominent paradigms of aging and age related conditions is the progressive accumulation of un-repaired DNA breaks leading to apoptosis and exhaustion of stem cells. Here we hypothesized that B lymphocytes from old mice have reduced DNA repair mechanisms as a contributing factor for DNA break accumulation. We analyzed class switch recombination (CSR) of naïve B lymphocytes from old and adult mice to delineate the DNA double strand repair mechanisms during aging. In vitro CSR assays and DNA break analysis by labeling phosphorylated histone H2AX showed that old mice had significantly reduced DNA repair efficiency following DNA breaks. Functional efficiency analysis of DNA break repairs using plasmid ligation method showed that B lymphocytes from old mice had poor repair efficiency and increased misrepair of linear plasmid. Diminished DNA repair in old age can contribute to reduced immune cell repertoire and impaired immunity; increased occurrence of cancer; and reduced stem cell reserve.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Puthiyaveetil AG,Caudell DL

doi

10.1016/j.molimm.2012.07.001

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

79-87

issue

1-2

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(12)00347-1

journal_volume

53

pub_type

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