Genome-wide Profiles of DNA Damage Represent Highly Accurate Predictors of Chronological Age
Accurate prediction of a true biological age of an individual represents a very important problem for both the clinics and basic science, as well as for the society as a whole, which led to a wealth of efforts to identify multiple types of various age-related biomarkers. However, the predictive models based on these biomarkers still require major improvements calling for identification of novel age-related biomarkers. Despite multiple studies associating DNA damage with aging, a glaring paucity of DNA damage-based age-related biomarkers exist, in no small part 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. Here, we explored the potential of the data generated using these methods as the source of universal age biomarkers in mammals. Strikingly, we found that patterns of either DNA lesion could very accurately predict age with higher precision than the commonly used transcriptome analysis. These findings show that previously unexplored high-resolution patterns of genome-wide DNA damage contain potential treasure troves of useful information that can significantly enrich both practical applications and basic science Overall design: An in-depth analysis of the genome-wide profiles of SSBs, AP sites and RNA from several tissues of mice collected from animals of various ages in order to evaluate the potential of DNA damage-based chronological age predictors and to compare their performance to the predictors based on transcriptome.