The reproductive system of human female exhibits a much faster rate of aging than other body systems.Ovarian aging is thought to be dominated by a gradual decreasing numbers of follicles,coinciding with diminished qua...The reproductive system of human female exhibits a much faster rate of aging than other body systems.Ovarian aging is thought to be dominated by a gradual decreasing numbers of follicles,coinciding with diminished quality of oocytes.Menopause is the final step in the process of ovarian aging.This review focuses on the mechanisms underlying the ovarian aging involving a poor complement of follicles at birth and a high rate of attrition each month,as well as the alternated endocrine factors.We also discuss the possible causative factors that contribute to ovarian aging,e.g.,genetic factors,accumulation of irreparable damage of microenvironment,pathological effect and other factors.The appropriate and reliable methods to assess ovarian aging,such as quantification of follicles,endocrine measurement and genetic testing have also been discussed.Increased knowledge of the ovarian aging mechanisms may improve the prevention of premature ovarian failure.展开更多
Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries,and the aging process is accompanied by changes in gut microbiota composition.However,little is known about the ...Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries,and the aging process is accompanied by changes in gut microbiota composition.However,little is known about the relationship between gut microbiota and ovarian aging.By using fecal microbiota transplantation(FMT)to transplant material from young(5-week-old)into aged(42-week-old)mice,we find that the composition of gut microbiota in FMT-treated mice presents a“younger-like phenotype”and an increase of commensal bacteria,such as Bifidobacterium and Ruminococcaceae.Moreover,the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ.Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group.Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice.Our results also show that FMT improves the immune microenvironment in aged ovaries,with decreased macrophages and macrophage-derived multinucleated giant cells(MNGCs).These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.展开更多
Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the microenvironment w...Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the microenvironment where stem cells reside in vivo, the secreted factors to which stem cells are exposed, thehypoxic environment, and intracellular factors including genome stability, mitochondria integrity, epigenetic regulators, calorie restrictions, nutrients, and vitamin D. Secreted tumor growth factor-β and fibroblast growth factor-2 are reported to play a role in stem cell quiescence. Extracellular matrices may interact with caveolin-1, the lipid raft on cell membrane to regulate quiescence. N-cadherin, the adhesive protein on niche cells provides support for stem cells. The hypoxic micro-environment turns on hypoxia-inducible factor-1 to prevent mesenchymal stem cells aging through p16 and p21 down-regulation. Mitochondria express glucosephosphate isomerase to undergo glycolysis and prevent cellular aging. Epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 help maintain stem cell quiescence. In addition, calorie restriction may lead to secretion of paracrines cyclic ADP-ribose by intestinal niche cells, which help maintain intestinal stem cells. In conclusion, it is crucial to understand the anti-aging phenomena of stem cells at the molecular level so that the key to solving the aging mystery may be unlocked.展开更多
Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and ...Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.展开更多
Background:Bladder cancer(BLCA)is the most common malignancy of the urinary system.Muscle-invasive bladder cancer(MIBC),which constitutes approximately 25%of all BLCA cases,is characterized by frequent recurrence and ...Background:Bladder cancer(BLCA)is the most common malignancy of the urinary system.Muscle-invasive bladder cancer(MIBC),which constitutes approximately 25%of all BLCA cases,is characterized by frequent recurrence and early onset of metastasis.Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging.However,the prognostic value of age-related genes in BLCA,especially in MIBC,remains unclear.Materials and methods:Training and testing sets were obtained from The Cancer Genome Atlas BLCA project.Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes.Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures,followed by the construction of a risk score model and nomogram.Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power.An independent BLCA cohort of 165 samples was included for external validation.The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment.Results:Seven genes(IGF1,NGF,GCLM,PYCR1,EFEMP1,APOC3,and IFNB1)were identified by Cox and least absolute shrinkage and selection operator analyses.After combining the gene signature with the clinical parameters of patients with BLCA,a risk-prognosis model and nomogram were constructed and validated with the testing set.Bladder cancer cases with high 7-gene signature scores(high-risk group)and low scores(low-risk group)showed distinct prognoses.Furthermore,7 types of immune cells were significantly altered between the low-and high-risk groups.Conclusions:Collectively,our data provide a 7-gene signature that serves as a potential biomarker for BLCA,especially MIBC.Moreover,this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.展开更多
基金supported by the National Basic Research Program of China (Grant Nos. 2012CB944402,2011CB944501 and 2007CB947401)Program of Knowledge Innovation of Chinese Academy of Sciences (GrantNo. KSCX2-EW-R-07)
文摘The reproductive system of human female exhibits a much faster rate of aging than other body systems.Ovarian aging is thought to be dominated by a gradual decreasing numbers of follicles,coinciding with diminished quality of oocytes.Menopause is the final step in the process of ovarian aging.This review focuses on the mechanisms underlying the ovarian aging involving a poor complement of follicles at birth and a high rate of attrition each month,as well as the alternated endocrine factors.We also discuss the possible causative factors that contribute to ovarian aging,e.g.,genetic factors,accumulation of irreparable damage of microenvironment,pathological effect and other factors.The appropriate and reliable methods to assess ovarian aging,such as quantification of follicles,endocrine measurement and genetic testing have also been discussed.Increased knowledge of the ovarian aging mechanisms may improve the prevention of premature ovarian failure.
基金supported by the National Key Research and Development Program of China(2018YFC1003703-1)the National Natural Science Foundation of China(81871628,82172288,81902027)。
文摘Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries,and the aging process is accompanied by changes in gut microbiota composition.However,little is known about the relationship between gut microbiota and ovarian aging.By using fecal microbiota transplantation(FMT)to transplant material from young(5-week-old)into aged(42-week-old)mice,we find that the composition of gut microbiota in FMT-treated mice presents a“younger-like phenotype”and an increase of commensal bacteria,such as Bifidobacterium and Ruminococcaceae.Moreover,the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ.Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group.Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice.Our results also show that FMT improves the immune microenvironment in aged ovaries,with decreased macrophages and macrophage-derived multinucleated giant cells(MNGCs).These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.
基金Supported by A grant from the National Science Council,Taiwan
文摘Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the microenvironment where stem cells reside in vivo, the secreted factors to which stem cells are exposed, thehypoxic environment, and intracellular factors including genome stability, mitochondria integrity, epigenetic regulators, calorie restrictions, nutrients, and vitamin D. Secreted tumor growth factor-β and fibroblast growth factor-2 are reported to play a role in stem cell quiescence. Extracellular matrices may interact with caveolin-1, the lipid raft on cell membrane to regulate quiescence. N-cadherin, the adhesive protein on niche cells provides support for stem cells. The hypoxic micro-environment turns on hypoxia-inducible factor-1 to prevent mesenchymal stem cells aging through p16 and p21 down-regulation. Mitochondria express glucosephosphate isomerase to undergo glycolysis and prevent cellular aging. Epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 help maintain stem cell quiescence. In addition, calorie restriction may lead to secretion of paracrines cyclic ADP-ribose by intestinal niche cells, which help maintain intestinal stem cells. In conclusion, it is crucial to understand the anti-aging phenomena of stem cells at the molecular level so that the key to solving the aging mystery may be unlocked.
基金supported by the National Natural Science Foundation of China(82003228)the Natural Science Foundation of Jiangsu Province(BK20201080)the Research Project of Clinical Medical Science and Technology Development Fund of Jiangsu University(JLY2021097).
文摘Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.
基金supported by the Natural Science Foundation of Shandong Province(ZR2020QH240)the National Natural Science Foundation of China(82002719).
文摘Background:Bladder cancer(BLCA)is the most common malignancy of the urinary system.Muscle-invasive bladder cancer(MIBC),which constitutes approximately 25%of all BLCA cases,is characterized by frequent recurrence and early onset of metastasis.Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging.However,the prognostic value of age-related genes in BLCA,especially in MIBC,remains unclear.Materials and methods:Training and testing sets were obtained from The Cancer Genome Atlas BLCA project.Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes.Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures,followed by the construction of a risk score model and nomogram.Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power.An independent BLCA cohort of 165 samples was included for external validation.The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment.Results:Seven genes(IGF1,NGF,GCLM,PYCR1,EFEMP1,APOC3,and IFNB1)were identified by Cox and least absolute shrinkage and selection operator analyses.After combining the gene signature with the clinical parameters of patients with BLCA,a risk-prognosis model and nomogram were constructed and validated with the testing set.Bladder cancer cases with high 7-gene signature scores(high-risk group)and low scores(low-risk group)showed distinct prognoses.Furthermore,7 types of immune cells were significantly altered between the low-and high-risk groups.Conclusions:Collectively,our data provide a 7-gene signature that serves as a potential biomarker for BLCA,especially MIBC.Moreover,this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.
