A High‐throughput Targeted Bisulfite Sequencing‐based Analysis for Epigenetic Age Quantification and Monitoring

Abstract

Aging represents the most important risk factor for many chronic diseases including cardiovascular diseases, diabetes, and cancer, therefore understanding the mechanisms of aging is a fundamental step for designing new treatments for chronic diseases. DNA methylation is the most reliable and accurate molecular marker for aging quantification, however, genome‐wide DNA methylation profiling techniques, such as reduced representative bisulfite sequencing and Illumina Bead Array that are widely used in aging research are prohibitively expensive and have poor data quality at low‐read coverage sites. Here we report a robust targeted bisulfite sequencing approach, called SWARM™ (Simplified Whole‐panel Amplification Reaction Method), for the accurate biological age determination. SWARM™ is flexible and low cost, requires relatively low DNA input, allows the simultaneous amplification and sequencing of hundreds of loci, and has shown to increase sample throughput. Using the SWARM™ approach, we were able to analyze the methylation level of several hundreds of age‐associated loci including the published Horvath Clock sites. An age‐predictive model was built using the elastic net regression of DNA methylation levels of the loci and chronological age of blood DNA samples of over 300 healthy subjects of 18 to 89 years old. Our epigenetic age (DNAge™) predictor achieved a small median age error, and the DNAge™ of samples that were processed on both sequencing and array platforms highly correlated (r > 0.9). In brief, our versatile SWARM™ technology‐based DNAge™ platform is a very fast and accurate tool for the precise biological aging quantification and aging interventions monitoring. Dedicated DNAge™ platforms are compatible with various sample types, and can be applied for aging studies in human, and in other species including mice.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.