Molecular Mechanisms of Age-Related Cardiac Hypertrophy in the F344XBN Rat Model

Background: The aging heart undergoes well characterized changes in cardiac structure and function. Recent studies suggest that age-related increase in oxidative stress is associated with increased cardiomyocyte apoptosis and possible compensatory hypertrophy of the remaining cardiomyocytes. However, the underlying molecular mechanisms remain obscure. The purpose of this study is to examine the possible molecular mechanisms underlying the age-related hypertrophy seen in male F344XBN rat hearts. Methods and results: Male F344XBN rats aged 6, 27, 30, 33, and 36-months were divided into five groups and were used to examine the molecular mechanisms underlying age-associated cardiac hypertrophy through immunohistochemical staining and immunoblotting. Compared to 6-month animals, the heart to body weight ratio remained unchanged in the 27 and 30-month rats, while it was significantly increased by 27 ± 5% and 38 ± 7% in 33 and 36-month old rats, respectively (P<0.05). Consistent with these data, semi-quantitative morphological analysis suggested that the average cardiomyocyte fiber cross sectional area was five- and nine fold higher in the 33 and 36- month old animals, respectively (P<0.05). Increases in cardiomyocyte size were accompanied by the hyperphosphorylation of several different signalling molecules involved in the ERK 1/2- Akt signalling pathway (P<0.05). Conclusion: Taken together, these data suggest that age related cardiomyocyte hypertrophy in the F344XBN rat heart is associated with the alterations in ERK1/2 and Akt signalling.