Cytotoxicity and mutagenicity of endogenous DNA base lesions as potential cause of human aging

Endogenous factors constitute a substantial source of damage to the genomic DNA. The type of damage includes a number of different base lesions and single- and double-strand breaks. Unrepaired DNA damage can give rise to mutations and may cause cell death. A number of studies have demonstrated an association between aging and the accumulation of DNA damage. This may be attributed to reduced DNA repair with age, although this is apparently not a general feature for all types of damage and repair mechanisms. Therefore, detailed studies that improve our knowledge of DNA repair systems as well as mutagenic and toxic effects of DNA lesions will help us to gain a better insight into the mechanisms of aging. The aim of this review is to provide a brief description of cytotoxic and mutagenic endogenous DNA lesions that are mainly repaired by base excision repair and single-strand break repair pathways and to discuss the potential role of DNA lesions and DNA repair dysfunction in the onset of human aging. (C) 2008 Elsevier Ireland Ltd. All rights reserved.