Increasing mitochondrial protein activity can prolong healthy life span

Drosophila is an ideal biological model for the study of human behavior, development, genetics, metabolism and diseases The results of this study show that increasing sirt4 activity may be an important way to treat aging related diseases (such as diabetes and obesity) such as the decline of metabolic level and promote healthy longevity This paper was published in PNAS on January 29 "Sirt4 can regulate life span and metabolism, especially the metabolic response of the body to fasting," said Jason wood, a researcher in the Department of molecular biology, cell biology and biochemistry at Brown University and the first author of the article "Only overexpression of sirt4 gene can prolong the life span of Drosophila melanogaster." The transgenic flies expressing sirt4 had 20% more healthy lifespan than the same flies, on the contrary, the flies without sirt4 lived 20% less than the normal flies In addition, fruit flies that lack sirt4 cells can't help but starve Once they are deprived of food, they will die quickly, although they still have enough nutrition and fat Sirt4 is essentially a group of proteins called sirtuin s, which are known to regulate longevity, metabolism, genomic stability, diabetes and neurodegenerative diseases There are seven kinds of sirtuins in human cells Three of them (SIRT3, sirt4 and sirt5) are mitochondrial sirtuins However, Drosophila cells only contain one sirtuins, sirt4, which is also located in mitochondria, suggesting that human sirt4 may have similar effects "For the first time, we have shown that directly increasing mitochondrial protein in the body can prolong animal life," Wood said In addition, sirt4 is also involved in the regulation of Fasting Metabolism, holding the gene regulatory switch from carbohydrate to fat "Sirt4 acts like a 'fuel switch' during fasting," said Stephen Helfand, a professor of biology at Brown University and the author of the article's newsletter "Flies without sirt4 are unable to mobilize the nutrients and fats stored in their bodies." As we all know, a brief fast can reset the metabolism of the body Sirt4 activation seems to play a role between "hunger" and "healthy life" Scientists don't know exactly how the "fast anti-aging" mechanism works, and sirt4 may play an important role in it "We want to learn more about the role of sirtuins in the heat restriction pathway," Helfand said In addition, previous studies have shown that resveratrol can activate SIRT1 protein in mammals, thus delaying aging, anti-cancer and anti diabetes Now, scientists want to know what substance can activate sirt4 protein "Sirt4 is another potential target for improving basal metabolism and extending healthy lifespan," Helfand said "At present, in vivo experiments of Drosophila have proved the effect of sirt4, and we are not sure about its effect on mammals." The results of in vitro experiments on how mitochondrial sirtuins affect mammalian cell and tissue metabolism contradict those of Drosophila "Drosophila has only one mitochondrial sirtuin, and artificial intervention is relatively simple," Helfand said "So it is a direct tool for us to evaluate the main function of mitochondrial sirtuin." "This study is based on 'a complete animal model,'" Wood said "We observed the physiological consequences of inactivation or overexpression of the sirt4 gene in Drosophila." Sirtuin protein has been a research hotspot in the field of aging for many years The research results in vivo prove that sirtuin, including sirt4, is one of the promising targets for the prevention and treatment of human aging related diseases.