Suppression of phosphoinositide 3-kinase preserved cardiac function and attenuated expression of senescence markers associated with enhanced autophagy in aged mice.
Does suppression of phosphoinositide 3-kinase prevent age-associated molecular changes and preserve cardiac function in aged mice?
Suppression of phosphoinositide 3-kinase preserves cardiac function and prevents age-associated molecular changes in a murine model, suggesting a potential molecular target for age-related heart failure.
BACKGROUND: Heart failure is a typical age-associated disease. Although age-related changes of heart are likely to predispose aged people to heart failure, little is known about the molecular mechanism of cardiac aging. METHODS AND RESULTS: We analyzed age-associated changes in murine heart and the manner in which suppression of the p110alpha isoform of phosphoinositide 3-kinase activity modified cardiac aging. Cardiac function declined in old mice associated with the expression of senescence markers. Accumulation of ubiquitinated protein and lipofuscin, as well as comprehensive gene expression profiling, indicated that dysregulation of protein quality control was a characteristic of cardiac aging. Inhibition of phosphoinositide 3-kinase preserved cardiac function and attenuated expression of the senescence markers associated with enhanced autophagy. Suppression of target of rapamycin, a downstream effector of phosphoinositide 3-kinase, also prevented lipofuscin accumulation in the heart. CONCLUSIONS: Suppression of phosphoinositide 3-kinase prevented many age-associated changes in the heart and preserved cardiac function of aged mice.
Inuzuka et al. (Tue,) conducted a other in Cardiac aging. Suppression of the p110alpha isoform of phosphoinositide 3-kinase was evaluated on Cardiac function and expression of senescence markers. Suppression of phosphoinositide 3-kinase preserved cardiac function and attenuated expression of senescence markers associated with enhanced autophagy in aged mice.