Sirtuins against ischemia
Sirtuins are a family of proteins with anti–aging properties that are involved in the regulation of cell lifespan, metabolism and resistance to stress. A preclinical study by Ji Lee's group from the University of South Florida showed that increasing the levels of sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) in cardiomyocytes of elderly patients who have suffered a myocardial infarction is likely to help protect the heart from post-ischemic reperfusion syndrome.
An age-related decrease in the activity of the SIRT1 and SIRT3 genes weakens the ability of cardiomyocytes to contract with damage by the type of ischemia-reperfusion, or post-ischemic reperfusion syndrome. In addition, the deficiency of SIRT1 and SIRT3 leads to inhibition of the activity of mitochondria – intracellular energy stations. Because of this, the pumping function of the heart gradually decreases. Conversely, an increase in SIRT1 and SIRT3 levels restores healthy mitochondrial activity in cardiomyocytes.
Mitochondria produce the energy needed to regulate almost all processes in living cells. Cardiomyocytes contain more mitochondria than any other cells in the body, because the heart requires a large amount of energy to continuously push blood through all the vessels. The stable activity of mitochondria maintains a healthy balance between the processes of cleavage and synthesis in them.
Reperfusion is a tactic for the treatment of acute myocardial infarction aimed at restoring blood flow and, consequently, nutrition of the part of the heart that has suffered from coronary thrombosis. Paradoxically, in some patients, reperfusion causes further damage to the tissue of the heart muscle bordering the infarction zone. Currently, there are no effective methods for preventing post-ischemic reperfusion injury.
To analyze the mitochondrial response to reperfusion after ischemia, the researchers knocked out the SIRT1 or SIRT3 genes in mouse cardiomyocytes and simulated ischemic stress by limiting blood flow in coronary vessels. They found that mitochondria in cells lacking SIRT3 were more vulnerable to reperfusion stress, while mitochondria in cells with SIRT3 were preserved intact. In mice with the SIRT3 gene knocked out, the activity of mitochondria, as well as their shape, size and structure physiologically resembled those of old wild-type mice with preserved SIRT3.
In addition, young mice without SIRT1 or SIRT3 under post-ischemic reperfusion stress showed significantly weaker contractions of cardiomyocytes and cardiac dysfunction characteristic of the old organism appeared.
This study clarifies why older people have a higher heart attack rate than younger people, and why they die more often, even if they receive full-fledged treatment. One of the reasons may be an age-related decrease in the levels of SIRT1 and SIRT3 in cells.
The researchers note that increasing the levels of sirtuins before surgical restoration of blood flow in the coronary arteries in elderly patients may reduce the risk of post-ischemic reperfusion syndrome and reduce mortality. Such cardioprotective treatment may include gene therapy to increase the expression of SIRT1 and SIRT3 or the introduction of an agonist to activate the SIRT1 and SIRT3 genes.
Article by J.Zhang et al. Alterations in mitochondrial dynamics with age-related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility is published in the journal Aging Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of South Florida: Age-related decline in two sirtuin enzymes alters mitochondrial dynamics, weakens cardiac contracts.