Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks.Research on skeletal diseases caused by aging in humans is ch...Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks.Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations,difficulties in sampling,regional variability,and substantial investment.Consequently,mice are preferred for such studies due to their similar motor system structure and function to humans,ease of handling and care,low cost,and short generation time.In this review,we present a comprehensive overview of the characteristics,limitations,applicability,bone phenotypes,and treatment methods in naturally aging mice and prematurely aging mouse models(including SAMP6,POLG mutant,LMNA,SIRT6,ZMPSTE24,TFAM,ERCC1,WERNER,and KL/KL-deficient mice).We also summarize the molecular mechanisms of these aging mouse models,including cellular DNA damage response,senescence-related secretory phenotype,telomere shortening,oxidative stress,bone marrow mesenchymal stem cell(BMSC)abnormalities,and mitochondrial dysfunction.Overall,this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.展开更多
Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cell...Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of agingassociated disorders, but also in future development of novel effective stem cell-based therapies to treat agingassociated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.展开更多
Background Laminopathies are a group of rare genetic disorders characterized by multiple-tissue degeneration.We describe a new laminopathy with ovarian cystadenoma and explore its molecular etiology.Methods The case i...Background Laminopathies are a group of rare genetic disorders characterized by multiple-tissue degeneration.We describe a new laminopathy with ovarian cystadenoma and explore its molecular etiology.Methods The case is a 15-year-old girl who presents the prominent progeroid disorders, multiple system degeneration and early-onset cystadenoma of the ovary.Candidate genes including LMNA, ZMPSTE24, PPAR G, INSR and WRN were sequenced to screen for DNA variants.The mRNA and protein expression levels of LMNA were examined in primary fibroblasts.The pathophysiological events such as morphologic alterations, cell senescence, cell proliferation,apoptosis and pRb as well as p53 protein expressions were also investigated in primary fibroblasts.Results No mutation was identified in the candidate genes screened.Nuclear abnormalities including nuclear blebs,mislocalization of lamin A/C were evident in the patient fibroblasts.Ultrastructurally, nucleus exhibited nuclear herniation and almost complete loss of peripheral heterochromatin.In addition, lamin C protein expression was markedly reduced whereas lamin A protein level was normal and no prelamin A was detected in the primary fibroblasts.Although the senescence-associated β-galactosidase staining of patient＇ cells was negative, cells in S phase increased in accompany with a decrease in pRb protein expression.Furthermore, increases in apoptotic cell death and p53 expression were observed.Conclusions Our data suggest that selective deficiency of lamin C protein is associated with a case of laminopathy with ovarian cystadenoma.The abnormalities in nuclear structure and alterations in gene expression such as the decrease in pRb and increase in p53 may be responsible for the multiple tissue degeneration.展开更多
Air pollution adversely affects skin,leading to skin inflammation and premature skin aging.Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection o...Air pollution adversely affects skin,leading to skin inflammation and premature skin aging.Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection of skin from the damage by air pollutants.Our previous studies demonstrated that Averrhoa carambola fruit(known as star fruit)is rich in flavonoid C-glycosides with unique structures and potent antioxidant activity.Thus,the star fruit extract(SFE)and main flavonoid C-glycoside components,carambolasides I,J,and P(1-3),carambolaflavone B(4),and isovitexin 2″-O-α-l-rhamnoside(5),were investigated for the activity against air pollutant stress in human epidermis.As a result,SFE and compounds 1-5 exhibited significant inhibitory activity against protein carbonylation in oxidative-stressed stratum corneum with the best activity being shown by compound 3.SFE and compounds 2-5 were also active against engine exhaust-induced protein carbonylation in stratum corneum.When further evaluated,SFE and com-pound 3 significantly inhibited gene expression of the key inflammation mediators IL-1αand COX-2 in PM-stressed keratinocytes.The results indicated that SFE and the flavonoid C-glycosides are potentially effective against air pollutant-induced skin inflammation and premature aging.展开更多
Melatonin is an effective antioxidant hormone produced mainly by the pineal gland.Premature senescence refers to senescence induced by declined cell proliferation and physiological functions when cells are stimulated ...Melatonin is an effective antioxidant hormone produced mainly by the pineal gland.Premature senescence refers to senescence induced by declined cell proliferation and physiological functions when cells are stimulated by nontelomeric signals.The anti-aging effect of melatonin is exerted by upregulating the expression of silent information regulator 1/Sirtuin 1(SIRT1),which reduces oxidative stress damage,decreases p53 activation,and inhibits the NF-κB pathway.Radiation can induce premature senescence through direct or indirect oxidative stress damage.The mechanism by which melatonin regulates radiation-induced premature senescence includes the inhibition of the p53-mediated senescence pathway through elimination of reactive oxygen species or p53 deacetylation induced by upregulation of SIRT1 expression.Melatonin exhibits different regulatory effects for different cells and types of radiation.展开更多
基金National Natural Science Foundation of China(82272608)2021 Capacity Building of Shanghai Universities(21010503600)Shanghai Key Lab of Human Performance(Shanghai University of Sport)(11DZ2261100)。
文摘Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks.Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations,difficulties in sampling,regional variability,and substantial investment.Consequently,mice are preferred for such studies due to their similar motor system structure and function to humans,ease of handling and care,low cost,and short generation time.In this review,we present a comprehensive overview of the characteristics,limitations,applicability,bone phenotypes,and treatment methods in naturally aging mice and prematurely aging mouse models(including SAMP6,POLG mutant,LMNA,SIRT6,ZMPSTE24,TFAM,ERCC1,WERNER,and KL/KL-deficient mice).We also summarize the molecular mechanisms of these aging mouse models,including cellular DNA damage response,senescence-related secretory phenotype,telomere shortening,oxidative stress,bone marrow mesenchymal stem cell(BMSC)abnormalities,and mitochondrial dysfunction.Overall,this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.
文摘Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of agingassociated disorders, but also in future development of novel effective stem cell-based therapies to treat agingassociated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.
基金This study was supported by grants from the Science and Technology Planning Project of Guangdong Province, China （No.2008B030301335）, Natural Science Foundation of Guangdong Province, China （No.8151008901000196）, Medical Scientific Research Foundation of Guangdong Province, China （No.B2008045）, China Postdoctoral Science Foundation （No.20060390754） and Sanofi-aventis. We acknowledge with thanks for Prof. XIANG Kun-san from No. 6 People＇s Hospital of Shanghai Jiao Tong University with his kindly advices on this study, and Dr. LIU Dong-nian from the Second Affiliated Hospital of Guangzhou Medical College for his kindly cooperation. We also thank the patient and her family for their support.
文摘Background Laminopathies are a group of rare genetic disorders characterized by multiple-tissue degeneration.We describe a new laminopathy with ovarian cystadenoma and explore its molecular etiology.Methods The case is a 15-year-old girl who presents the prominent progeroid disorders, multiple system degeneration and early-onset cystadenoma of the ovary.Candidate genes including LMNA, ZMPSTE24, PPAR G, INSR and WRN were sequenced to screen for DNA variants.The mRNA and protein expression levels of LMNA were examined in primary fibroblasts.The pathophysiological events such as morphologic alterations, cell senescence, cell proliferation,apoptosis and pRb as well as p53 protein expressions were also investigated in primary fibroblasts.Results No mutation was identified in the candidate genes screened.Nuclear abnormalities including nuclear blebs,mislocalization of lamin A/C were evident in the patient fibroblasts.Ultrastructurally, nucleus exhibited nuclear herniation and almost complete loss of peripheral heterochromatin.In addition, lamin C protein expression was markedly reduced whereas lamin A protein level was normal and no prelamin A was detected in the primary fibroblasts.Although the senescence-associated β-galactosidase staining of patient＇ cells was negative, cells in S phase increased in accompany with a decrease in pRb protein expression.Furthermore, increases in apoptotic cell death and p53 expression were observed.Conclusions Our data suggest that selective deficiency of lamin C protein is associated with a case of laminopathy with ovarian cystadenoma.The abnormalities in nuclear structure and alterations in gene expression such as the decrease in pRb and increase in p53 may be responsible for the multiple tissue degeneration.
基金supported by an NSFC grant (No.31470423) and a special fund for natural resources affairs (2019KJCX027) from Forest Administration of Guangdong Province,China.
文摘Air pollution adversely affects skin,leading to skin inflammation and premature skin aging.Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection of skin from the damage by air pollutants.Our previous studies demonstrated that Averrhoa carambola fruit(known as star fruit)is rich in flavonoid C-glycosides with unique structures and potent antioxidant activity.Thus,the star fruit extract(SFE)and main flavonoid C-glycoside components,carambolasides I,J,and P(1-3),carambolaflavone B(4),and isovitexin 2″-O-α-l-rhamnoside(5),were investigated for the activity against air pollutant stress in human epidermis.As a result,SFE and compounds 1-5 exhibited significant inhibitory activity against protein carbonylation in oxidative-stressed stratum corneum with the best activity being shown by compound 3.SFE and compounds 2-5 were also active against engine exhaust-induced protein carbonylation in stratum corneum.When further evaluated,SFE and com-pound 3 significantly inhibited gene expression of the key inflammation mediators IL-1αand COX-2 in PM-stressed keratinocytes.The results indicated that SFE and the flavonoid C-glycosides are potentially effective against air pollutant-induced skin inflammation and premature aging.
基金This work was supported by the Beijing Municipal Natural Science Foundation(7202139 and 7162137)the National Natural Science Foundation of China(31570852).
文摘Melatonin is an effective antioxidant hormone produced mainly by the pineal gland.Premature senescence refers to senescence induced by declined cell proliferation and physiological functions when cells are stimulated by nontelomeric signals.The anti-aging effect of melatonin is exerted by upregulating the expression of silent information regulator 1/Sirtuin 1(SIRT1),which reduces oxidative stress damage,decreases p53 activation,and inhibits the NF-κB pathway.Radiation can induce premature senescence through direct or indirect oxidative stress damage.The mechanism by which melatonin regulates radiation-induced premature senescence includes the inhibition of the p53-mediated senescence pathway through elimination of reactive oxygen species or p53 deacetylation induced by upregulation of SIRT1 expression.Melatonin exhibits different regulatory effects for different cells and types of radiation.
