They identify a new molecular mechanism responsible for the aging of the heart

They identify a new molecular mechanism responsible for the aging of the heart https://i0.wp.com/www.eresviral.com/wp-content/uploads/2018/11/Identifican-un-nuevo-mecanismo-molecular-responsable-del-envejecimiento-del-corazón.jpg?fit=219%2C146&ssl=1

They identify a new molecular mechanism responsible for the aging of the heart





They identify a new molecular mechanism responsible for the aging of the heart


A study led by Marisol Ruiz-Meana, principal investigator of the group of Cardiovascular Diseases of the Vall d'Hebron Institute of Research (VHIR) led by David García-Dorado, in which the Protein Chemistry Group of the National Research Center has participated Cardiovascular (CNIC), both belonging to the CIBERCV, has discovered that the functional alterations of cardiac cells in aging are not explained by oxidative changes, but are due to the accumulation of advanced glycation products (AGEs). end-products) that is produced, in part, by a failure in the enzymatic system responsible for preventing damage by glycation.



As we age, the heart adapts worse to exercise and becomes more vulnerable to stress and ischemia damage. If we observe it at the cellular level, we see that, in the muscle cells of the heart, the cardiomyocytes, there is a progressive mismatch between their energy needs and the capacity to generate energy. This facilitates the development of contractile insufficiency, among other alterations. But the cellular mechanisms responsible for this deterioration are unknown, and until now the main hypothesis was the increase in oxidative damage associated with age.



In this study, published in the journal Circulation, has been identified "a new way to explain the process and the mechanisms that lead to an aged but healthy cardiomyocyte to become a deteriorated cardiomyocyte that predisposes the heart to develop heart failure", explains Marisol Ruiz-Meana







Researchers who have participated in the study. (Photo: CIBER)



"This new pathway is glycation, an unregulated chemical attack that produces irreversible and terminal alterations in proteins," he says. The study shows that gingival damage associated with aging affects the ryanodine receptor, the channel that controls the release of calcium from the sarcoplasmic reticulum, a network of ducts that extends throughout the cell and that releases and collects at each heartbeat. calcium to regulate the activation of contractile proteins and the production of energy (in the form of ATP) in mitochondria.



The study indicates that the ryanodine receptor is partially glycated in the cardiomyocytes of old mice (more than 20 months) and of patients older than 75 years. The glycation of the ryanodine receptor causes the closure of this channel to be defective, so that there is an uncontrolled release of calcium from the sarcoplasmic reticulum that ends up exposing the mitochondria to an excess of calcium. As a consequence, mitochondria accumulate calcium inside them and lose the respiratory capacity necessary to generate energy efficiently.



The researchers propose that this chain of alterations produced by glycation constitutes the pathophysiological basis of the functional deterioration of the heart during aging that, in turn, could facilitate the transition to heart failure, a condition that increases exponentially as we get older. and that it constitutes one of the main causes of death and disability in all the countries of the world. The identification of this molecular mechanism of cardiac aging could allow the development of treatments aimed at preventing it. (Source: CIBER / DICYT)

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