Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases serious...Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases seriously affect the quality of life and longevity of the population and place a huge burden on health care and economic systems around the world.Humans have two types of Psn,presenilin-1(PSEN1)and presenilin-2(PSEN2).Mutations in the genes encoding PSEN1,PSEN2,and amyloid precursor protein(APP)have been identified as the major genetic causes of AD.Psn is a complex gene strongly influenced by genetic and environmental factors.The effects of exercise,training,and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.Fortunately,relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal models,including Drosophila,mice,and other animals,all of which share orthologous genes of Psn with humans.Many previous studies have linked aging,exercise training,and a high-fat diet to the Psn gene.This review discusses the interrelationship between aging,exercise training,and a high-fat diet on the Psn gene and its associated disease,AD.The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for diseases caused by Psn gene mutations.展开更多
Aging decreases muscle mass,strength,and functional capacity.High-salt stress seems to promote muscle aging and decrease lifespan.However,exercise delays muscle aging and increases longevity,and it may protect muscle ...Aging decreases muscle mass,strength,and functional capacity.High-salt stress seems to promote muscle aging and decrease lifespan.However,exercise delays muscle aging and increases longevity,and it may protect muscle from rapid aging induced by high-salt intake(HSI),but the molecular mechanisms are poorly understood.In this study,the flies were fed a high-salt diet and trained to exercise.Muscle CG2196(salt)gene and dSir2 gene were over-expressed by building mef2-gal4/UAS system.The results showed that both physical exercise and muscle dSir2 gene overexpression prevented HSI-induced and muscle salt overexpression-induced accelerated age-related decline of climbing index,climbing endurance,muscle NAD^(+)level,SOD activity level,dSir2 expression,and dFOXO expression,and they also prevented HSI-induced and muscle salt overexpression-induced accelerated age-related increase in muscle ROS level,MDA level,and salt gene expression.Physical exercise improved lifespan decrease induced by HSI and muscle salt overexpression.Therefore,current results indicated that high-salt stress accelerated muscle aging by decreasing muscular NAD^(+)/dSir2/dFOXO pathway activity and increasing oxidative stress.Physical exercise protected muscle from accelerated aging induced by high-salt stress through activating muscle NAD^(+)/dSir2/dFOXO pathway and enhancing muscle oxidation resistance.The combination of exercise and muscle dSir2 overexpression had the best protective effect on muscle aging and lifespan in flies.展开更多
基金This work was supported by the National Natural Science Foundation of China[Grant No.32000832]the Shandong Province Natural Science Foundation[Grant No.ZR2020QC096].
文摘Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases seriously affect the quality of life and longevity of the population and place a huge burden on health care and economic systems around the world.Humans have two types of Psn,presenilin-1(PSEN1)and presenilin-2(PSEN2).Mutations in the genes encoding PSEN1,PSEN2,and amyloid precursor protein(APP)have been identified as the major genetic causes of AD.Psn is a complex gene strongly influenced by genetic and environmental factors.The effects of exercise,training,and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.Fortunately,relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal models,including Drosophila,mice,and other animals,all of which share orthologous genes of Psn with humans.Many previous studies have linked aging,exercise training,and a high-fat diet to the Psn gene.This review discusses the interrelationship between aging,exercise training,and a high-fat diet on the Psn gene and its associated disease,AD.The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for diseases caused by Psn gene mutations.
基金This work is supported by the National Natural Science Foundation of China(NSFC)(32000832)Province Natural Science Foundation of Shandong(ZR2020QC096).
文摘Aging decreases muscle mass,strength,and functional capacity.High-salt stress seems to promote muscle aging and decrease lifespan.However,exercise delays muscle aging and increases longevity,and it may protect muscle from rapid aging induced by high-salt intake(HSI),but the molecular mechanisms are poorly understood.In this study,the flies were fed a high-salt diet and trained to exercise.Muscle CG2196(salt)gene and dSir2 gene were over-expressed by building mef2-gal4/UAS system.The results showed that both physical exercise and muscle dSir2 gene overexpression prevented HSI-induced and muscle salt overexpression-induced accelerated age-related decline of climbing index,climbing endurance,muscle NAD^(+)level,SOD activity level,dSir2 expression,and dFOXO expression,and they also prevented HSI-induced and muscle salt overexpression-induced accelerated age-related increase in muscle ROS level,MDA level,and salt gene expression.Physical exercise improved lifespan decrease induced by HSI and muscle salt overexpression.Therefore,current results indicated that high-salt stress accelerated muscle aging by decreasing muscular NAD^(+)/dSir2/dFOXO pathway activity and increasing oxidative stress.Physical exercise protected muscle from accelerated aging induced by high-salt stress through activating muscle NAD^(+)/dSir2/dFOXO pathway and enhancing muscle oxidation resistance.The combination of exercise and muscle dSir2 overexpression had the best protective effect on muscle aging and lifespan in flies.