Objective To screen and validate aging-associated DNA methylation dysregulation and to establishconvenient, sensitive, accurate assays for detecting and screening substances capable of reversing dysregulated DNAmethylation associated with the aging process. Methods The Gene Expression Omnibus (GEO) database was used toscreen and validate DNA methylation alterations in the human aging process. A methylation qPCR detection system wasdeveloped to verify the correlation between DNA methylation levels of target genes and human age. Cancer cells were treatedwith a set of natural extracts/ substances that had anti-aging properties to detect their effects on DNA methylation levels oftarget gene and phenotypic changes. Results A methylation detection system for the secretagogin (SCGN) and integrinsubunit alpha 2b (ITGA2B) genes was established. Methylation levels of SCGN and ITGA2B genes were found to becorrelated with human age, which was verified in 53 independent samples. Epigallocatechin gallate (EGCG) and gallic acid(GA) inhibited the tumor cell survival and reversed SCGN and ITGA2B methylation dysregulation associated with aging.Conclusions Measurements of SCGN and ITGA2B methylation level changes may be used to monitor the aging process inhumans. They may also be used to provide experimental evidence for the development of anti-aging drugs or products based on DNA methylation regulation mechanisms.