The goal of this project is to identify novel genetic and metabolic factors that influence cellular stress resistance, organismal susceptibility to age-associated diseases, and organismal longevity. To achieve this goal we will employ comparative genomics and metabolomics analysis between different breeds of dogs at different ages. Dogs present an excellent model to study aging. Dogs have a similar physiology to that of human's; they naturally develop similar age-related disorders, including various cancers and cognitive impairments. Due to breeding efforts, dogs have the widest range of physiological parameters, including longevity. Finally, dogs and humans share the same environment and life routines, making the possible findings in this model organism the most relevant to human health. Section of Pathology at Cornell College of Veterinary Medicine assembled an archive of over 2000 formalin fixed paraffin embedded (FFPE) canine brains and continues to update the collection on the ongoing bases. The archive contains samples from dogs of different ages and different breeds. Using this collection and the lllumina high-throughput RNA sequencing technology we will perform a comparative longitudinal study to identify and characterize gene expression dynamics in the brains of dogs of various breeds and ages in vivo. By comparing longitudinal gene expression dynamics between long-lived and short-lived dog breeds, we will be able to identify gene candidates (both protein coding and non-coding RNAs) that contribute to brain aging or can serve as biomarker of aging. By comparing breeds with high and low susceptibility to gliomas we will additionally suggest novel genes, which connect advanced age to increased incidences of brain tumors.