Genome-Wide Integrative Transcriptional Profiling Identifies Age-Associated Signatures in Dogs

Mammals experience similar stages of embryonic development, birth, infancy, youth, adolescence, maturity, and senescence. While embryonic developmental processes have been extensively researched, many molecular mechanisms regulating the different life stages after birth, such as aging, remain unresolved. We investigated the conserved and global molecular transitions in transcriptional remodeling with age in dogs of 15 breeds, which revealed that genes underlying hormone level regulation and developmental programs were differentially regulated during aging. Subsequently, we show that the candidate genes associated with tumorigenesis also exhibit age-dependent DNA methylation patterns, which might have contributed to the tumor state through inhibiting the plasticity of cell differentiation processes during aging, and ultimately suggesting the molecular events that link the processes of aging and cancer. These results highlight that the rate of age-related transcriptional remodeling is influenced not only by the lifespan, but also by the timing of critical physiological milestones.