目的:观察六味地黄丸方对秀丽隐杆线虫寿命、生殖力、运动能力的影响并探讨其可能的分子机制。方法:秀丽隐杆线虫分为空白对照组、六味地黄丸方高、中、低剂量组(160、80、40 mg·m L-1)。寿命实验观察各组线虫平均寿命;生殖能力测...目的:观察六味地黄丸方对秀丽隐杆线虫寿命、生殖力、运动能力的影响并探讨其可能的分子机制。方法:秀丽隐杆线虫分为空白对照组、六味地黄丸方高、中、低剂量组(160、80、40 mg·m L-1)。寿命实验观察各组线虫平均寿命;生殖能力测试中,计数各组总子代数目;运动能力实验测试各组线虫20 s内身体弯曲的次数。实时荧光定量PCR(Real-Time PCR)方法检测空白组和六味地黄丸方中剂量组的daf-2 m RNA、daf-16 m RNA表达变化。结果:与空白组比较,六味地黄丸方中、低剂量组均能延长线虫的平均寿命(P<0.01),以中剂量组更为显著,并可明显提高线虫生殖高峰期及末期的生殖能力。与空白组比较,各剂量组均使线虫运动能力明显减缓(P<0.01);用药组daf-2 m RNA表达明显下调(P<0.05);daf-16 m RNA表达明显上调(P<0.05)。结论:六味地黄丸方能明显延长秀丽隐杆线虫寿命,其机制可能与下调daf-2基因和上调daf-16基因表达有关。展开更多
The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caeno...The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.展开更多
Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,e...Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.展开更多
Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inf...Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inflammation, wounds, and bacterial infections, as well as aging. α-mangostin is an abundant xanthone in the pericarp, and is thought to play a critical role in the medicinal effects of mangosteens. Previous studies have demonstrated numerous beneficial effects of α-mangostin, such as cytotoxicity in cancer cells. However, the effects of this xanthone in in vivo have not yet been studied. In the current study, C. elegans was used to test the in vivo effects of α-mangostin using several bioassays, including fat accumulation, pharyngeal movement (pumping) and heat-stress assays. Quantitative real time PCR (qRT-PCR) was also used to examine the expression of heat shock proteins. The results revealed that α-mangostin appeared to cause an increase in fat accumulation, which correlated with an increase in pharyngeal movement. The thrashing movement of the worms after heat stress also showed a correlation with an increase in heat shock protein mRNA expression.展开更多
Purification of biomass ethanol from the products of brown sugar yeast-fermentation produces a large amount of residue. This fermentation residue contains abundant brown sugar-derived nutrients and is mainly used as c...Purification of biomass ethanol from the products of brown sugar yeast-fermentation produces a large amount of residue. This fermentation residue contains abundant brown sugar-derived nutrients and is mainly used as compost or livestock feed. However, the in vivo physiological effects of oral residue ingestion are not known. The purpose of this study was to elucidate the physiological action and molecular mechanism of fermented brown sugar residue in nematode stress tolerance, aging, and lifespan using Caenorhabditis elegans. Fermented brown sugar residue was divided into two layers, supernatant and precipitate, and each was given to nematodes. Analysis of motility and survival rate under thermal stress revealed reduced mobility and increased survival rate following treatment with fermented brown sugar residue. The survival rate of nematodes under 1% H2O2 was markedly increased by the residue and mitochondrial membrane depolarization was induced and mitochondrial radical oxygen species levels increased. Furthermore, aging dependent reduction of motility was suppressed, and the average life span of nematodes was extended by treatment with fermented brown sugar residue. Moreover, the effects of fermented brown sugar residue on stress tolerance, lifespan elongation, and decreased aging dependent momentum reduction were lost in the daf-16 mutant. Taken together, our results show that the various physiological actions of fermented brown sugar residue, including stress tolerance and lifespan extension, occur via DAF-16.展开更多
Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medi...Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.展开更多
文摘目的:观察六味地黄丸方对秀丽隐杆线虫寿命、生殖力、运动能力的影响并探讨其可能的分子机制。方法:秀丽隐杆线虫分为空白对照组、六味地黄丸方高、中、低剂量组(160、80、40 mg·m L-1)。寿命实验观察各组线虫平均寿命;生殖能力测试中,计数各组总子代数目;运动能力实验测试各组线虫20 s内身体弯曲的次数。实时荧光定量PCR(Real-Time PCR)方法检测空白组和六味地黄丸方中剂量组的daf-2 m RNA、daf-16 m RNA表达变化。结果:与空白组比较,六味地黄丸方中、低剂量组均能延长线虫的平均寿命(P<0.01),以中剂量组更为显著,并可明显提高线虫生殖高峰期及末期的生殖能力。与空白组比较,各剂量组均使线虫运动能力明显减缓(P<0.01);用药组daf-2 m RNA表达明显下调(P<0.05);daf-16 m RNA表达明显上调(P<0.05)。结论:六味地黄丸方能明显延长秀丽隐杆线虫寿命,其机制可能与下调daf-2基因和上调daf-16基因表达有关。
基金the National Key R&D Program of China(2021YFA0805802 to D.C.)the National Natural Science Foundation of China(31971092 and 32171156 to D.C.)Some strains were provided by the Caenorhabditis Genetics Center(CGC),which is funded by NIHOffice of Research Infrastructure Programs(P40 OD010440).
文摘The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.
基金This study was supported by the Key Research Project Fund of Beijing University of Chinese Medicine(2021JYB2002001)the National Natural Science Foundation of Tibetan medicine Collabo-rative Innovation(82130113).
文摘Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.
文摘Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inflammation, wounds, and bacterial infections, as well as aging. α-mangostin is an abundant xanthone in the pericarp, and is thought to play a critical role in the medicinal effects of mangosteens. Previous studies have demonstrated numerous beneficial effects of α-mangostin, such as cytotoxicity in cancer cells. However, the effects of this xanthone in in vivo have not yet been studied. In the current study, C. elegans was used to test the in vivo effects of α-mangostin using several bioassays, including fat accumulation, pharyngeal movement (pumping) and heat-stress assays. Quantitative real time PCR (qRT-PCR) was also used to examine the expression of heat shock proteins. The results revealed that α-mangostin appeared to cause an increase in fat accumulation, which correlated with an increase in pharyngeal movement. The thrashing movement of the worms after heat stress also showed a correlation with an increase in heat shock protein mRNA expression.
文摘Purification of biomass ethanol from the products of brown sugar yeast-fermentation produces a large amount of residue. This fermentation residue contains abundant brown sugar-derived nutrients and is mainly used as compost or livestock feed. However, the in vivo physiological effects of oral residue ingestion are not known. The purpose of this study was to elucidate the physiological action and molecular mechanism of fermented brown sugar residue in nematode stress tolerance, aging, and lifespan using Caenorhabditis elegans. Fermented brown sugar residue was divided into two layers, supernatant and precipitate, and each was given to nematodes. Analysis of motility and survival rate under thermal stress revealed reduced mobility and increased survival rate following treatment with fermented brown sugar residue. The survival rate of nematodes under 1% H2O2 was markedly increased by the residue and mitochondrial membrane depolarization was induced and mitochondrial radical oxygen species levels increased. Furthermore, aging dependent reduction of motility was suppressed, and the average life span of nematodes was extended by treatment with fermented brown sugar residue. Moreover, the effects of fermented brown sugar residue on stress tolerance, lifespan elongation, and decreased aging dependent momentum reduction were lost in the daf-16 mutant. Taken together, our results show that the various physiological actions of fermented brown sugar residue, including stress tolerance and lifespan extension, occur via DAF-16.
基金the Yunnan provincial government(20080A007)the 100 Talents Program of the Chinese Academy of Sciences,the State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany(P2008-ZZ21 and T2009-KF05)。
文摘Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.
