Whole-genome sequencing in aging research

Whole-genome sequencing (WGS) generates complete base-pair-resolution data across nuclear and mitochondrial DNA, enabling discovery of rare coding and non-coding variants, structural variants, and copy-number changes that are invisible to SNP arrays. In aging research, WGS has several distinct applications: it identifies rare longevity-associated variants in centenarian families and cohorts (e.g., protective mutations in PCSK9, APOC3, or DNA repair genes) that require deep sequencing to detect; it quantifies somatic mutation burden and clonal hematopoiesis of indeterminate potential (CHIP) in aging tissues, linking somatic evolution to cardiovascular and cancer risk; and it maps mitochondrial heteroplasmy dynamics that accumulate with age. Sequencing costs have fallen from ~$3,000/Gb in 2008 toward approximately $1–5/Gb by the mid-2020s depending on platform and throughput, making population-scale WGS studies feasible; however, interpreting variants of uncertain significance (VUS) and managing incidental findings remain major clinical and ethical challenges, especially as WGS enters preventive medicine for healthy aging populations.