Genome-wide profiles of DNA damage represent highly accurate predictors of mammalian age.

Abstract

The identification of novel age-related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage-based biomarkers of age, mainly due to the lack of precise methods for genome-wide surveys of different types of DNA damage. Recently, we developed two techniques for genome-wide mapping of the most prevalent types of DNA damage, single-strand breaks and abasic sites, with nucleotide-level resolution. Herein, we explored the potential of genomic patterns of DNA damage identified by these methods as a source of novel age-related biomarkers using mice as a model system. Strikingly, we found that models based on genomic patterns of either DNA lesion could accurately predict age with higher precision than the commonly used transcriptome analysis. Interestingly, the informative patterns were limited to relatively few genes and the DNA damage levels were positively or negatively correlated with age. These findings show that previously unexplored high-resolution genomic patterns of DNA damage contain useful information that can contribute significantly to both practical applications and basic science.