A study led by Dr. Marisol Ruiz-Meana, principal investigator of the group of Cardiovascular Diseases of the Vall d'Hebron Institute of Research (VHIR) led by Dr. David García-Dorado, in collaboration which the Chemistry Group of Proteins from the National Center for Cardiovascular Research (CNIC), both belonging to the CIBERCV of the ISCIII, has discovered that the functional alterations of cardiac cells in aging are not explained by oxidative changes, but to the accumulation of advanced products of the glycation (AGEs, Advanced Glycation End-products) that takes place, partly, by a fault in the enzymatic system in charge to prevent the 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, 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 an increase in oxidative damage associated with age.In this study, published in the journal https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.118.035869" 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, which predisposes the heart to develop heart failure", explains Dr. Marisol Ruiz-Meana."This new pathway is glycation, an unregulated chemical attack that produces irreversible and terminal alterations in proteins" she explains. 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 that releases and collects with each heartbeat. That mechanism regulates the activation of contractile proteins and the production of energy (in the form of ATP) in mitochondria.The study indicates that the ryanodine receptors are partially glycated in the cardiomyocytes of old mice (more than 20 months) and of older patients over 75 years. The glycation of the ryanodine receptor causes the closure of these channels, which become 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 in excess with the consequent loss of its 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. Heart failure constitutes one of the main causes of death and disability, considered as a global pandemic affecting at least 26 million worldwide. The identification of this molecular mechanism of cardiac aging could allow the development of treatments to prevent preventing the major health threat in the developed world.