Across numerous disciplines and breeds, tendinopathies in recreational and elite athletes is an ongoing issue due to inadequate therapeutics from the poor healing capacity of tendons. The structure and function of the tendon throughout development, maturation, homeostasis, aging, and injury heavily depends on the roles of the tendon proper (TP) and peritenon (PERI) cell populations in tendons. Understanding the molecular and cellular levels of the tendinopathies and the changes that the TP and PERI cell populations undergo during aging may further elucidate age-dependent alterations in tendon architecture and functionality. We hypothesize that as tendons age, the cells’ responses to the surrounding niche environment could be affected by reduced representation bisulfite sequencing (RRBS) targeted methylation sites like promoters and thereby affecting gene expression. Further, we hypothesize that adolescent (0–5 year), midlife (6–14 year), and geriatric (15–27 year) tendons can be categorized based on gene expression and methylation silencing and correlate to changes in genes vital to tendon health and healing. For this study, the RNA and DNA of the superficial digital flexor tendon (SDFT) from 9 non-breed or sex specific samples for adolescent (TP, n = 3; PERI, n = 3), midlife (TP, n = 3; PERI, n = 3), and geriatric (TP, n = 3; PERI, n = 3) horses were isolated for gene expression by RNaseq and methylated residues by RRBS. The workflow for RNaseq utilized Trimmomatic, Salmon, and the R package DESeq2 to identify the differentially expressed genes (DEG) across age groups and cell type, gene ontology by PANTHER, and pathway analysis through Advaita iPathway. RRBS post-analysis used Trim Galore! and Bismark to quantify CpG islands and percent methylation. Preliminary analysis of the transcriptome showed clear separation of the TP and PERI groups regardless of age by principal component and heatmap analysis. Gene ontology and DEG showed fewer expression differences for midlife (110 DEGs) samples as compared with adolescent (978 DEGs) or geriatric (970 DEGs) in both TP and PERI. These initial findings indicate distinct transcriptomic differences in the tendon proper and peritenon cell populations, in addition to, age related changes occurring more prominenty during adolescent and geriatric compared with midlife. By combining the transcriptome and methylome analysis in horses across age, we would be able to target age-related regulations by identifying gene enrichment changes occurring with age for future therapeutics to improve tendon repair by exogenous gene products.