Effect of dietary polyunsaturated fatty acids on age-related changes in cardiac mitochondrial membranes.
Remodeling of myocardial cell membranes is a major feature of advanced age. Mitochondrial function, crucial to sustaining energy production and management of myocardial metabolism, is impacted by age-dependent remodeling and ultimately exhibits a diminished threshold for excess Ca2+ buffering during events that stimulate increased myocardial Ca2+, such as augmented cardiac work, oxidative stress or post-ischemic reflow. Relative Ca2+, intolerance, augmented superoxide formation and reduced efficiency in the management of reactive oxygen species, are important mitochondrial factors (of many) that are apparent in senescence and predispose the myocardium to be more vulnerable 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 mitochondrial membrane changes include increases in membrane rigidity, cholesterol, phosphatidylcholine, omega-6 polyunsaturated fatty acids (PUFA), 4-hydroxy-2-nonenal, and decreases in omega-3 PUFA and cardiolipin. These effects have been shown in animal studies to be exaggerated by diet rich in long chain omega-6 PUFA (i.e. arachidonic acid), and 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.
Pepe
Salvatore
S
Department of Cardiothoracic Surgery, Alfred Hospital, Melbourne, Vic., Australia. spepe@baker.edu.au
D000368:Aged; D000375:Aging / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D016922:Cellular Senescence; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D002308:Cardiolipins; D004042:Dietary Fats, Unsaturated; D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D002118:Calcium