Reproductive aging is a natural process conserved across species and is well-known in females.It shows age-related follicle depletion and reduction of oocyte quality,eventually causing reproductive senescence and meno...Reproductive aging is a natural process conserved across species and is well-known in females.It shows age-related follicle depletion and reduction of oocyte quality,eventually causing reproductive senescence and menopause.Although reproductive aging in males is not well noticed as in females,it also causes infertility and has deleterious consequences on the offspring.Various factors have been suggested to contribute to reproductive aging,including oxidative stress,mitochondrial defects,telomere shortening,meiotic chromosome segregation errors and genetic alterations.With the increasing trend of pregnancy age,it is particularly crucial to find interventions to preserve or extend human fertility.Studies in humans and model organisms have provided insights into the biological pathways associated with reproductive aging,and a series of potential interventive strategies have been tested.Here,we review factors affecting reproductive aging in females and males and summarize interventive strategies that may help delay or rescue the aging phenotypes of reproduction.展开更多
Bazi Bushen(BZBS),a traditional Chinese medicine(TCM),has demonstrated therapeutic efficacy in testicular dysfunction within D-galactose and NaNO_(2)mouse models.This study aimed to ascertain if BZBS could also mitiga...Bazi Bushen(BZBS),a traditional Chinese medicine(TCM),has demonstrated therapeutic efficacy in testicular dysfunction within D-galactose and NaNO_(2)mouse models.This study aimed to ascertain if BZBS could also mitigate the decline in testicular function associated with natural aging.Therefore,male aged mice were employed to evaluate the preventive effects of BZBS on male reproductive aging.This was achieved by assessing sex hormone production,testicular histomorphology,and spermatogenesis.Relative to the untreated aged control group,BZBS administration elevated the levels of sex hormones and spermatocyte populations and preserved normal testicular structure in aged mice.Notably,spermatogenesis was maintained.Further analyses,including malondialdehyde(MDA)assays and real-time PCR,indicated that BZBS diminished testicular oxidative stress and the inflammatory burden.Corroborating these findings,mice treated with BZBS exhibited reductions in the populations of senescent and apoptotic cells within the seminiferous tubules,suggesting alleviated cellular damage.In contrast,we observed that rapamycin,a drug known for its longevity benefits,induced excessive testicular apoptosis and did not decrease lipid peroxidation.Collectively,our results highlight BZBS’s promising clinical potential in counteracting male reproductive aging,underlining its mechanisms of action.展开更多
The frequency of aneuploid gamete formation increases with maternal age,yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood.Using the multicellular orga...The frequency of aneuploid gamete formation increases with maternal age,yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood.Using the multicellular organism Caenorhabditis elegans,we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors.Point mutations in the head domain of the cohesin component SMC-1,which alter local hydrophobicity,cause meiotic defects that vary with age.A severe mutation causes incomplete synapsis and defective crossover formation,and a minor one causes age-related diakinesis bivalent abnormalities.Notably,while the mild mutation causes defects only in aged worms,worms with the severe mutation exhibit significantly alleviated phenotypes with age.Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase,which restores impaired cohesin loading.These findings reveal that cohesin variants,meiotic progression speed during early prophase,and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.展开更多
基金supported by grants from the National Natural Science Foundation of China(32022018 and 31871360 to J.Gao)。
文摘Reproductive aging is a natural process conserved across species and is well-known in females.It shows age-related follicle depletion and reduction of oocyte quality,eventually causing reproductive senescence and menopause.Although reproductive aging in males is not well noticed as in females,it also causes infertility and has deleterious consequences on the offspring.Various factors have been suggested to contribute to reproductive aging,including oxidative stress,mitochondrial defects,telomere shortening,meiotic chromosome segregation errors and genetic alterations.With the increasing trend of pregnancy age,it is particularly crucial to find interventions to preserve or extend human fertility.Studies in humans and model organisms have provided insights into the biological pathways associated with reproductive aging,and a series of potential interventive strategies have been tested.Here,we review factors affecting reproductive aging in females and males and summarize interventive strategies that may help delay or rescue the aging phenotypes of reproduction.
基金This work was supported by the Strategic Consulting Project of the Chinese Academy of Engineering-Strategic Research(No.2022-XY-45)the S&T Programs of Hebei Province,China(Nos.E2020100001 and 22372502D)+2 种基金the High-level S&T Innovation and Entrepreneurship Talent Project of Shijiazhuang City(No.07202203)the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine(No.2023172)the Natural Science Foundation of Hebei Province,China(No.H2022106065)。
文摘Bazi Bushen(BZBS),a traditional Chinese medicine(TCM),has demonstrated therapeutic efficacy in testicular dysfunction within D-galactose and NaNO_(2)mouse models.This study aimed to ascertain if BZBS could also mitigate the decline in testicular function associated with natural aging.Therefore,male aged mice were employed to evaluate the preventive effects of BZBS on male reproductive aging.This was achieved by assessing sex hormone production,testicular histomorphology,and spermatogenesis.Relative to the untreated aged control group,BZBS administration elevated the levels of sex hormones and spermatocyte populations and preserved normal testicular structure in aged mice.Notably,spermatogenesis was maintained.Further analyses,including malondialdehyde(MDA)assays and real-time PCR,indicated that BZBS diminished testicular oxidative stress and the inflammatory burden.Corroborating these findings,mice treated with BZBS exhibited reductions in the populations of senescent and apoptotic cells within the seminiferous tubules,suggesting alleviated cellular damage.In contrast,we observed that rapamycin,a drug known for its longevity benefits,induced excessive testicular apoptosis and did not decrease lipid peroxidation.Collectively,our results highlight BZBS’s promising clinical potential in counteracting male reproductive aging,underlining its mechanisms of action.
基金supported by grants from the National Natural Science Foundation of China(32370780 and 32022018)the National Key Research and Development Program of China(2021YFA1101001)+1 种基金the Taishan Scholars Program Special FundSome strains were provided by the CGC,which is funded by NIH Office of Research Infrastructure Programs(P40 OD010440).
文摘The frequency of aneuploid gamete formation increases with maternal age,yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood.Using the multicellular organism Caenorhabditis elegans,we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors.Point mutations in the head domain of the cohesin component SMC-1,which alter local hydrophobicity,cause meiotic defects that vary with age.A severe mutation causes incomplete synapsis and defective crossover formation,and a minor one causes age-related diakinesis bivalent abnormalities.Notably,while the mild mutation causes defects only in aged worms,worms with the severe mutation exhibit significantly alleviated phenotypes with age.Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase,which restores impaired cohesin loading.These findings reveal that cohesin variants,meiotic progression speed during early prophase,and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.