The real human heart and soul is a exceptional muscle, beating more than 2 billion times over the common life span.
However the heart’s efficiency can lower as time passes. One major contributor to the diminished function is cardiac hypertrophy ï¿½ a thickening of the heart and soul muscle, producing a cut down in how big is the right and kept ventricles. This makes the heart and soul work and pump less blood vessels per circuit when compared to a healthy heart and soul harder.
Cornell researchers, employed in collaboration with experts in Switzerland, have discovered a strong interconnection between a health proteins, SIRT5, and healthy heart and soul function. SIRT5 has the capacity to remove a unsafe protein adjustment known as lysine succinylation, which robs the heart and soul of its potential to burn essential fatty acids efficiently to create the energy necessary for pumping.
“Our research shows that perhaps a method to improve heart and soul function is to discover a way to boost SIRT5 activity,” said Hening Lin, professor of substance and chemistry biology, who co-wrote this article shared online April 5 in the Proceedings of the Country wide Academy of Sciences.
Sushabhan Sadhukhan, a postdoctoral fellow in Lin’s lab, was lead author of the paper.
SIRT5 is one of a class of seven proteins called sirtuins that have been shown to influence a range of cellular processes. According to Sadhukhan, most research on laboratory mice into sirtuin activity has focused on the liver, as opposed to the heart, due to the size of the liver and ease of obtaining tissue.
Lin’s lab tested mouse tissue from five locations (heart, liver, kidney, brain, muscle) and found that protein lysine succinylation occurs to the greatest extent in the heart. The testing involved mice that had SIRT5 deleted.
The removal of SIRT5 resulted in reduced activity of ECHA, a protein involved in fatty acid oxidation, and decreased levels of adenosine triphosphate (ATP), which stores and transfers chemical energy within cells.
The effect of SIRT5 removal on heart function was even more pronounced as the mice aged. The researchers performed echocardiography on 8-week-old mice, with some reduced cardiac function observed. The mice were tested again at 39 weeks, and they showed hallmarks of cardiac hypertrophy ï¿½ increased heart weight and left ventricular mass, along with reductions in both the shortening and ejection fractions of the heart.
The group’s findings could spawn new methods for the preservation of heart health and extension of healthy life, which could have significant implications for human health. According to the Centers for Disease Control and Prevention, heart disease is the leading cause death among both men and women, with more than 600,000 people in the U.S. dying from it annually.
Lin said that vitamin B3, also known as niacin, boosts the production of the small molecule nicotinamide adenine dinucleotide (NAD), a coenzyme found in all living cells. SIRT5, like all sirtuins, is NAD-dependent.
“If you can have a way to promote sirtuin activity, like by taking a vitamin supplement, or somehow improving sirtuin levels, you might have healthier cells and organs and lengthen your healthy life,” Lin said.
His Swiss collaborator concurred.
“The identification of this new role of SIRT5 in cardiomyopathy assigns an important role of this ‘druggable’ enzyme in one of the major cardiac diseases,” said Johan Auwerx of the Ecole Polytechnique Fï¿½dï¿½rale de Lausanne. “It can be expected that pharmacological interference with these pathways will lead to new therapies for cardiomyopathy that, therefore, can lengthen healthy life span.”
SIRT5 regulation of proteins involved in metabolism
Sushabhan Sadhukhan et al. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function, Proceedings of the National Academy of Sciences (2016). DOI: 10.1073/pnas.1519858113