Aging and Dietary Lipids Modulate Ca2+-Dependent Mitochondrial Function in the Post-Ischemic Heart
A key feature of advanced age is a reduced threshold for excess Ca2+ loading during events that stimulate increased Ca2+ entry, such as augmented cardiac work, oxidative stress or post-ischemic reflow. Remodeling of myocardial cell membranes is a major factor underlying the relative Ca2+ intolerance in senescence and greater vulnerability to ischemic injury. In addition to cell death, surviving myocytes increase in size and exhibit altered gene expression of key effector proteins, including those that sustain Ca2+ homeostasis. Age-associated membrane changes, that may also be influenced by diet, include increases in membrane rigidity, cholesterol, phosphatidylcholine, omega-6 polyunsaturated fatty acids (PUFA), 4-hydroxy-2-nonenal, and decreases in omega-3 PUFA, cardiolipin. These alterations have profound consequences on the efficacy of membrane proteins involved with ion homeostasis, signal transduction, redox reactions and oxidative phosphorylation. However, some of the age-related detrimental adaptations may be beneficially modified by dietary strategy. Diet rich in omega-3 PUFA reverses the age-associated membrane omega-3: omega-6 PUFA imbalance, and dysfunctional Ca2+ metabolism, facilitating increased efficiency of mitochondrial energy production and improved tolerance of ischemia and reperfusion.
Key wordsomega-3 polyunsaturated fatty acids cardiolipin mitochondria calcium
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