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    Home > Biochemistry News > Biotechnology News > What are the causes of vascular aging? The expression of the longevity gene FOXO3A is reduced.

    What are the causes of vascular aging? The expression of the longevity gene FOXO3A is reduced.

    • Last Update: 2020-08-04
    • Source: Internet
    • Author: User
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    Cardiovascular disease is known as the "number one killer" of human health, and it is estimated that the number of people suffering from cardiovascular disease in China exceeds 290 million.
    vascular aging is one of the main factors leading to cardiovascular disease, then, what is the cause of vascular aging? On May 5, a study published by Chinese scholars in the journal Nature-Communications for the first time mapped the expression of single-celled genes in primate arterial vascular aging, revealing that the expression reduction of the longevity gene FOXO3A is the driving force of vascular aging. Qu Jing, a
    paper correspondent and a researcher at the Institute of Zoology of the Chinese Academy of Sciences, told The Chinese Journal of the degenerative changes in vascular structure and function that accompany aging as a major risk factor for cardiovascular disease.
    however, due to the high heterogeneity of vascular wall cells from different sources, the cell composition and molecular characteristics of the blood vessels in human geriatrics have not been clarified in previous studies, which has restricted the understanding of vascular aging mechanism and the development of related disease intervention methods.
    in the study, the researchers first conducted histological analyses of the aortic arches and coronary artery blood vessels of young and elderly crab-eating monkeys.
    using techniques such as 3D reconstruction of large-scale electromirrors, the researchers found that older blood vessels exhibitaging aging characteristics such as thickening of blood vessel walls, calcification, fibrosis, and degeneration of endothelial cells in blood vessels. although
    are susceptible parts of human atherosclerosis, but responsible for the body for most organs of the aorta and blood supply to the heart of the coronary artery of the two ages speed is different, cell composition, physiological characteristics are also different.
    to overcome the problem of tissue and cell heterogeneity and further clarify the molecular changes of the different types of vascular cells associated with aging, the researchers used single-cell transcription sequencing techniques to map the expression of blood vessel types such as aortic arches and coronary arteries, smooth muscle cells and fibroblasts, and identified eight new molecular markers that distinguish aorta and coronary artery cells.
    the analysis of the differential gene expression network associated with aging, the transcription factor FOXO3A (protein product encoded by the longevity gene FOXO3A) is the key molecular node to regulate the gene network of arterial vascular difference expression.
    FOXO3A is an important feature of primate arterial vascular aging in six types of aging vascular wall cells.
    , by combining embryonic stem cell gene editing and directional induced differentiation techniques, the researchers obtained a target to remove human vascular endothelial cells that knock off the FOXO3A gene.
    the loss of vascular endothelial cells in FOXO3A showed degradation of proliferation, migration, and tube formation compared to wild-type cells that did not knock out the FOXO3A gene.
    after being transplanted into the ischemic hind limbs of mice, FOXO3A's missing human endothelial cells also had significantly less vascular repair capacity than wild-type cells.
    taking into account differences in vascular biology and aging characteristics between rodents and primates, the team chose crab-eating monkeys with a closer physiological structure than humans.
    This is also the first time that the single cell map of primate vascular aging has been reported in the world, and the change systres of cell composition and molecular characteristics in the process of primate vascular aging are analyzed.
    With the rapid aging of the global population, aging research has become a hot topic.
    FOXO3A is a "star" gene in the field of aging genetics, and its genetic polymorphism is closely related to human health and longevity.
    in this study, researchers have for the first time demonstrated the important role of FOXO3A in maintaining the steady state of primate arterial blood vessels.
    co-authors of the study were Qu Jing, Liu Guanghui, a researcher at the Institute of Zoology of the Chinese Academy of Sciences, and Tang Fuhui, a professor at Peking University.
    2019, the team reported in Cell-Stem Cells that gene editing technology was used to obtain the world's first FOXO3A genetically enhanced human vascular cells.
    , contrary to the missing vascular cells of FOXO3A, FOXO3A enhanced cells have significantly enhanced vascular repair capabilities, providing a high-quality cell transplantation material for the treatment of vascular degenerative diseases through regenerative medicine.
    the study was carried out by the Institute of Stem Cell and Regenerative Medicine Innovation of the Chinese Academy of Sciences, the Institute of Zoology of the Chinese Academy of Sciences, the Beijing Genomics Institute of the Chinese Academy of Sciences, Peking University, the Institute of Biophysics of the Chinese Academy of Sciences, the Institute of Automation of the Chinese Academy of Sciences, and the Xuanwu Hospital of capital medical university.
    Zhang Weixuan, a researcher at the Beijing Genomics Institute of the Chinese Academy of Sciences, Zhang Shu, a doctoral student at Peking University, Yan Pengze, a doctoral student at the Institute of Zoology of the Chinese Academy of Sciences, and Ren Jie, a doctoral student at Peking University, were the first authors.
    related paper information: related research: Chinese scientists found that the new anti-aging target gene is not old, youth forever, this is the eternal pursuit of ancient and modern Chinese and foreign human beings.
    to strive for a healthy and long life, and now our researchers have made new progress -- discovering a series of genes that potentially regulate behavioral degradation in the aging process, and identifying two epigenetic regulatory factors that can accelerate behavioral degradation in the aging process, which is likely to become an anti-aging drug target.
    , nature, a leading international scientific journal, published a paper online entitled "Two conservative epigenetic control factors hinder healthy aging."
    notable, one of the epigenetic regulatory factors not only accelerates cognitive behavioral degradation in the aging process, but also is positively correlated with the alzheimer's disease (Alzheimer's) process.
    " suggests that these genes, which can be targeted by anti-aging drugs, are likely to be targeted for screening drugs for the treatment of geriatric diseases.
    ," the team said.
    it is understood that the paper was completed by the Chinese Academy of Sciences Brain Science and Intelligent Technology Excellence Innovation Center, Shanghai Brain Science and Brain Research Center, Neuroscience National Key Laboratory Cai Shiqing Research Group and the Chinese Academy of Sciences Shanghai Pasteur Institute Jiang Lubin Research Group.
    history of aging is a time gone, and the years are relentless.
    quietly, the former like a flower-like girl became a wrinkled old man, once Yushu wind-facing young people no longer walk.
    When did we start getting old? Is there any way to slow down aging? For thousands of years, people have been searching for answers.
    late 1930s, scientists found that restricting diets extended the lifespan of mice and rats, suggesting that aging is a plastic process.
    with the emergence of new experimental methods, people have a better understanding of the phenomenon of aging from the individual to the cellular and molecular levels, scientists have put forward a number of theories to try to explain aging, but usually only part of the aging phenomenon.
    the 1990s, with the development of molecular biology, aging research entered the genetic age.
    a landmark work: In 1983, a scientist identified the first long-lived mutant in a model animal nematode, a gene mutation called age-1, which extended the life of nematodes by 40 to 60 percent.
    discovery has shocked many scientists: mutations in a single gene can change the length of life.
    in the decades that followed, scientists discovered hundreds of longevity genes that gave a certain understanding of the biological mechanisms of longevity.
    However, recent studies have found that some longevity genes, while extending life, do not necessarily delay the degradation of animal behavior and cognitive function.
    in other words, not commensurate with the significant increase in human life expectancy, the incidence of aging-related degenerative diseases in the elderly increased significantly with age.
    and there is very little research on the mechanism of healthy aging. What are the mechanisms by which
    organisms degrade their behavior in the aging process? In the face of the global aging population, how to improve the related functional degradation, and ultimately reduce the occurrence of geriatric diseases? In this way, there is a study at the beginning of the article. "We hope to improve the quality of life of older people and achieve old age,"
    .
    " is a paper correspondent and research group leader of the Center for Excellence in Brain Science and Intelligent Technology (Institute of Neuroscience) at the Chinese Academy of Sciences.
    genetics to screen for thousands of "needle in a haystack" gene, how to find the one that degrades a particular regulatory behavior? Genetic screening is a very important and effective method in biology to achieve "needle in a haystack".
    in model organisms commonly used for genetic screening, the researchers chose nematodes as their subjects.
    Cai Shiqing explained that this choice is because nematodes are small in size, body length of only 1 mm, easy to cultivate, genetic background and easy to genetic operation, and short life cycle; even so
    , it's not that simple to detect behavioral changes in aging.
    , then, is there a biological marker of aging that is easy to track, reflects the degradation of behavioral function and is suitable for large-scale screening? Cai Shiqing thought of the neurotransmitter system. what is neurotransmitter
    ? The first author of the paper, The Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligent Technology, Dr. Yuan Jie introduced, this is the mediaset between the brain neurons signal inglionation of the chemical, in the aging process, neurotransmitter dysfunction will lead to behavioral function degradation.
    existing studies have shown that improving neurotransmitter function can improve the behavioral ability of older people.
    , then, with neurotransmitter function as an indicator, Cai Shiqing's research team screened and looked for genes that regulate aging, and eventually obtained 59 candidate genes, 49 of which were the first to be found to affect the aging process.
    by building a network of interactions between candidate genes, the researchers found that two of the epigenetic regulators BAZ-2 and SET-6 were at the key nodes of the regulatory network.
    the next study, which found that the absence of mutant nematodes of BAZ-2 and SET-6, which degrades much more slowly with aging than wild nematodes, also extends life.
    " suggests that these two genes accelerate aging, and that reducing their function can slow down.
    ," Yuan Said.
    , however, another question surfaced at the same time: How do these two anti-aging target genes regulate aging? Through sequence analysis, Cai Shiqing's research team found that these two genes may be epigenetic regulatory factors.
    so-called epigenetic regulation, refers to the absence of changes in the dna sequence of the gene, gene expression has a genetic change, and eventually led to the change of phenotype.
    time is not in love.
    with the assistance of Jiang Lubin's Research Laboratory at the Shanghai Pasteur Institute of science, the team found that BAZ-2 and SET-6 can change the aging process by regulating mitochondrial function.
    mitochondria are the main place of cell metabolism, and a large number of studies have shown that the decrease of mitochondrial function during aging is an important reason for the deterioration of tissue function.
    ", by detecting nematodes' mitochondrial function, we found that knocking out the BAZ-2 and SET-6 genes did improve mitochondrial function and slow down behavior degradation.
    these results show that in order to improve the behavior function of the elderly individual, the activation of mitochondria needs to be activated.
    ," Cai said.
    has a new breakthrough in regulating aging research is still not over.
    after all, nematodes and human relatives are relatively far away, these two anti-aging target genes in mammals do not play the same role? The team further found that the human homologous genes baz-2 and SET-6, respectively, were BAZ2B and EHMT1, and that their expression in the human brain increased with aging.
    to test whether reducing BAZ2B's function can also fight aging, the researchers built mice that had been knocked out by the BAZ2B gene.
    three years passed because of the long reproductive cycle of mice, which have a life cycle of up to three years , and the researchers were pleasantly surprised to find that reducing the baz2B function in mice slowed the increase in weight in mice with age.
    what excites Cai, behavioral tests showed that older BAZ2B knockout mice maintained better cognitive abilities than wild mice.
    What does it mean? "BAZ2B and EHMT1 are important factors for regulating the aging process and are the new anti-aging target genes.
    ", Explains Cai Shiqing.
    toward the unknown, the team began exploring changes in the two anti-aging target genes in Alzheimer's disease.
    found that in the brains of Alzheimer's patients, the amount of expression of BAZ2B and EHMT1 was positively correlated with the disease progression, and negatively related to the expression of key mitochondrial proteins.
    ", this suggests that increased expression of BAZ2B and EHMT1 in the aging brain may be an important cause of mitochondrial defects in Alzheimer's disease and play an important role in its occurrence and development.
    ," Yuan Said.
    in Cai Shiqing's view, geriatric neurodegenerative diseases occur in the aging brain environment, so understanding the regulatory mechanisms of brain aging is essential to prevent and control these brain diseases.
    the study reveals the genetic regulatory network of nervous system aging, discovers BAZ2B, a new anti-aging target, and clarifies its role in cognitive aging, providing a new theoretical basis and action target for delaying brain aging.
    but he stressed that the study still has some limitations.
    , for example, no human validation.
    considering the large species differences between model organisms such as humans and mice, there is still considerable uncertainty as to whether these studies will be applied in humans.
    , for example, the current study focuses only on two epigenetic regulatory factors that have a clear regulatory effect on behavioral degradation, and for other screening possible genes, there is still no one-to-one validation, and no more mechanisms to regulate behavioral degradation in the aging process cannot be found.
    ", we decided on whether the epigenetic regulatory factors found in Alzheimer's model mice could affect the behavior of mental decline in the disease and explore its mechanisms, and tried to target the epigenetic regulatory factors found to screen small molecule drugs that regulate behavior degradation during aging or disease.
    ," Cai said.
    Source: Economic Daily Shen Hui China Science Daily Chen Huanhuan.
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