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Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
Published on: August 28, 2016
Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice
Yasutaka Inuzuka1, Junji Okuda, Tsuneaki Kawashima
1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Insights
Targeting phosphoinositide 3-kinase (PI3K) activity in aging hearts preserves cardiac function and prevents age-related decline. Inhibiting PI3K enhances autophagy and reduces senescence markers in aged mice.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Molecular Cardiology
Background:
- Heart failure is common in aging populations.
- Molecular mechanisms of cardiac aging remain poorly understood.
- Age-related cardiac changes predispose individuals to heart failure.
Purpose of the Study:
- Investigate age-associated cardiac changes in mice.
- Determine the effect of inhibiting phosphoinositide 3-kinase (PI3K) activity on cardiac aging.
- Elucidate the molecular pathways involved in cardiac aging.
Main Methods:
- Analyzed age-related changes in murine heart function and senescence markers.
- Assessed protein quality control through ubiquitinated protein and lipofuscin accumulation.
- Utilized gene expression profiling to understand molecular alterations.
- Inhibited PI3K activity and downstream target of rapamycin (mTOR) pathways.
Main Results:
- Cardiac function declined in aged mice, correlating with senescence markers.
- Dysregulated protein quality control, indicated by protein aggregates and lipofuscin, characterized cardiac aging.
- PI3K inhibition preserved cardiac function and reduced senescence markers.
- Enhanced autophagy was observed with PI3K inhibition.
- mTOR suppression prevented lipofuscin accumulation.
Conclusions:
- Suppression of PI3K activity effectively counteracted age-associated cardiac decline in mice.
- PI3K inhibition preserves cardiac function and mitigates molecular aging hallmarks in the heart.
- Targeting PI3K signaling represents a potential therapeutic strategy for age-related heart conditions.
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.
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