中国器官衰老与器官退行性变化的机制研究进展

Progress in the research of organ aging and the related degenerative diseases in China

急剧发展的人口老龄化已经成为我国社会发展面临的重大问题,也是今后相当长一段时期中国的基本国情.我国人口老龄化的不断加剧和老年慢性疾病发生率的快速升高,大大促进了我国在衰老与相关重大慢性疾病的发生机制和干预领域的研究.国家自然科学基金委员会自2016年起,通过采取一系列资助措施,使我国在器官衰老与器官退行性变化领域的基础和临床研究均得到快速发展和提升,并取得一系列令人瞩目的成果,达到国际领先水平.本文综述了近年来我国在器官衰老和神经退行性疾病研究领域的进展,包括器官衰老与器官退行性疾病的发生机制、器官衰老与器官退行性疾病的生物标志物和早期预警、衰老与退行性疾病的干预策略等,简要地介绍我国器官衰老研究的新成果、新动态,同时对未来的衰老研究方向和趋势进行展望.

Rapid development of population aging has already become a major problem in China,and it is also the China’s basic national condition for a considerable period of time in the future.The continuous aggravation of aging population and the rapid increase in the incidence of chronic diseases in the elderly have greatly promoted the research on the mechanism and intervention of organ aging and related diseases in China.Organ aging causes progressive functional decline and increases the risk of related diseases,which is the common pathogenic basis of many chronic diseases in the elderly.During aging,specific genetic and environmental factors cause progressive organ failure such as loss of nerve conductive function,vascular endothelial degeneration,increase in tube wall hardness,muscle atrophy,protein and lipid metabolism disorders,reduced production and secretion of hormones,reproductive dysfunction,osteoporosis,and structural and functional changes in other tissues.Without effective intervention,the above organ dysfunction will further induce a series of chronic diseases,including cardiovascular diseases,lung diseases,neurodegenerative diseases,metabolic syndrome and reproductive endocrine diseases.Therefore,the intervention of organ aging and its gradually development into organ degeneration is the key to prevent age-related diseases.In addition,the molecular mechanism of organ aging and degeneration is complicated,which is mainly manifested as damage accumulation and homeostasis disequilibrium,such as(1)chromosome damage,gene mutation and epigenetic abnormality,(2)accumulation of lipid peroxidation products and lipofuscin caused by mitochondrial damage and reactive oxygen species,(3)diabetes caused by hyperglycemia and accumulation of glycosylation end products in various cells and tissues,(4)aggregation of misfolded protein and denaturized and insoluble polymers,(4)abnormal transport of small molecules,(5)disturbed removal or recycling of damaged cells,organelles,proteins and other large molecules,(6)tissue inflammation and imbalance of cell interaction and homeostasis,and(7)decline in body homeostasis caused by imbalanced hormone and immune cells.Therefore,it is necessary to systematically study the changes in the genome,proteome,metabolome,structural and functional changes of organelles and cellular signal transduction network during the aging process for elucidating the mechanism of the deterioration from organ aging to degeneration.Since 2016,the National Natural Science Foundation of China has adopted a series of funding strategies to rapidly develop and improve basic and clinical research in the field of organ aging and organ degeneration in China,which lead to a series of remarkable scientific and technological achievements.This review summarizes the recent progress in the field of organ aging and neurodegenerative diseases in China,including the mechanisms,the biomarkers and the intervention strategies.We also briefly prospect the direction and trend of future research on organ aging and the related degenerative diseases.