ABSTRACT
Understanding the molecular mechanisms underlying age-related changes in the heart is challenging due to the contributions from numerous genetic and environmental factors. Genetically diverse outbred mice provide a model to study the genetic regulation of aging processes in healthy tissues from individuals undergoing natural aging in a controlled environment. We analyzed transcriptome and proteome data from outbred mice at 6, 12 and 18 months of age to reveal a scenario of cardiac hypertrophy, fibrosis, extracellular matrix remodeling, and reemergence of fetal gene expression patterns. We observed widespread changes in protein trafficking and sorting, and post-translational disruption of the stoichiometry of the protein quality control system itself. We identified genome hotspots of age-by-genetic effects that regulate proteins from the proteasome and endoplasmic reticulum stress response, suggesting that genetic variation in these modules may contribute to individual variation in the aging heart.
Competing Interest Statement
The authors have declared no competing interest.
