1 Introduction Recent studies have revealed that patterns of DNA methylation (DNAm) in mammalian cells change predictably with age (Horvath and Raj 2018; Lu et al. 2023). Typically, over 75% of cytosines in cytosine-phosphate-guanine (i.e., CpG) sites are methylated in an individual, but DNAm tends to decline with age across the genome (Unnikrishnan et al. 2018). However, at some sites, especially those in CpG-dense promoter regions, i.e., CpG islands (Day et al.