OBJECTIVES: To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis. METHODS: C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs). RESULTS: Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans. CONCLUSIONS BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals ; Caenorhabditis elegans/physiology* ; Ferroptosis/drug effects* ; Alpinia/chemistry* ; Sitosterols/pharmacology* ; Longevity/drug effects* ; Fruit/chemistry* ; Humans

Sophora moorcroftiana (S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans (C. elegans). Polysaccharides from S. moorcroftiana seeds (SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol (4 mg·mL). In SMpol (4 mg·mL) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.
Animals ; Caenorhabditis elegans ; drug effects ; physiology ; Longevity ; drug effects ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Reproduction ; drug effects ; Seeds ; chemistry ; Sophora ; chemistry ; Stress, Physiological ; drug effects

The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase (SOD) activities and intracellular reactive oxygen species (ROS) levels were investigated. The ERF-mediated change in SOD-3 expression was examined using GFP-expressing transgenic strain. The effects of ERF on the aging-related factors were investigated by reproduction assay and pharyngeal pumping assay. The intestinal lipofuscin levels of aged nematodes were also measured. The mechanistic studies were performed using selected mutant strains. Our results indicated that ERF showed potent lifespan extension effects on the wild-type nematode under both normal and various stress conditions. The ERF treatment also enhanced the activity and expression of superoxide dismutase (SOD) and attenuated the intracellular ROS levels. Moreover, ERF-fed nematodes showed decreased lipofuscin accumulation, indicating ERF might affect age-associated changes in C. elegans. The results of mechanistic studies indicated that there was no significant lifespan extension in ERF-treated daf-2, age-1, sir-2.1, and daf-16 null mutants, suggesting that they were involved in ERF-mediated lifespan regulation. In conclusion, R. fasciculatum confers increased longevity and stress resistance in C. elegans via SIR-2.1-mediated DAF-16 activation, dependent on the insulin/IGF signaling pathway.
Aging ; drug effects ; genetics ; metabolism ; Animals ; Caenorhabditis elegans ; drug effects ; genetics ; growth & development ; metabolism ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; Humans ; Longevity ; drug effects ; Oxidative Stress ; drug effects ; Plant Extracts ; pharmacology ; Reactive Oxygen Species ; metabolism ; Ribes ; chemistry ; Signal Transduction ; drug effects

OBJECTIVETo evaluate the effect of compound bushen recipe (CBR) in improving the survival state of stress and the overall life span in C. elegans by simulating chronic fatigue syndrome (CFS) under various stress states.

METHODSThe tolerance and the average survival time of adult larvae against heat stress (35 degrees C), oxidative stress (250 microg/mL juglone), and in vivo Abeta protein toxicity (Abeta(1-42) transgenic mutant CL4176) under the intervention of the high (500 mg/L), middle (250 mg/L), and low (100 mg/L) dose CBR were observed. The effect of CBR on the average live time (at 25 degrees C), movement distance in 20 seconds, the frequency of pharyngeal pump in 30 seconds, and the reproductive capability were assessed.

RESULTSCompared with the control group, the survival time of heat stressed C. elegans could be significantly increased in each CBR group (P < 0.01). The survival time of heat stressed C. elegans could be elongated, the protein toxicity be attenuated, and the live time prolonged in the high and middle dose CBR groups (P < 0.01, P < 0.05).The movement distance and the frequency of pharyngeal pump could also be increased in the high dose CBR group (P < 0.01). There was no statistical difference in the reproductive capability among all groups (P > 0.05).

CONCLUSIONSCBR could significantly enhance the stress capacity of C. elegans against internal and external environment, and prolong their lifespan. It did not interfere their normal production, and also could improve the quality of life, thus laying a foundation for further mechanism studies and pharmacological researches on CBR in preventing and treating CFS.

Animals ; Caenorhabditis elegans ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fatigue Syndrome, Chronic ; drug therapy ; Longevity ; Stress, Physiological

AIM: To investigate antioxidant activities and life span prolonging effects of the extracts from the roots of Incarvillea younghusbandii Sprague, and to study the correlations between these activities and the polar intensity of the extracts. METHOD: Five extracts (IYS1, IYS2, IYS3, IYS4 and YS5) with different polar intensity were prepared. Antioxidant activities in vitro were determined by LPO inhibitory and free radicals scavenging experiments. Life span prolonging effects in vivo were evaluated by feeding Drosophila melanogaster. RESULT: Total phenolic content in extracts were solvent-dependent and decreased in the order of IYS4 > IYS1 > IYS3 > IYS5 > IYS2. Organic extracts (IYS1 and IYS4) showed excellent LPO inhibitory activity, O(2)(· -) and ·OH scavenging activity compared to ascorbic acid (or benzoic acid, or BHT), while aqueous extracts (IYS2, IYS3 and IYS5) did not. The antioxidant activities (in vitro) were solvent dependent and decreased in the order of IYS4 > IYS1 > IYS3 > IYS5 ≥ IYS2. Drosophila melanogaster was fed with organic extracts (IYS1 or IYS4) at 5.0 mg mL(-1). The mean life span were increased by 24.4% (IYS1) or 23.0% (IYS4) in female and 15.3% (IYS1) or 16.9% (IYS4) in male; the maximum life span were increased by 8.4% (IYS1) or 11.2% (IYS4) in female and 9.7% (IYS1) or 15.8% (IYS4) in male, and the survival curves were significantly shifted to the right after fifteen days in both sexes survival period. Feeding aqueous extracts (IYS2, IYS3 or IYS5) at 5.0 mg·mL(-1), the significant life span prolonging effects were not achieved. The life span prolonging effects of the extracts were solvent-dependent and decreased in the order of IYS4 ≥ IYS1 > IYS3 > IYS2 > IYS5. CONCLUSION Extracts from the roots of Incarvillea younghusbandii Sprague showed excellent antioxidant activities and significant life span prolonging effects in Drosophila melanogaster. Positive correlations existed between the antioxidant activities and total phenolic content. Life span prolonging effect was positively correlated with the total phenolic content or antioxidant activities. The extracts possess better life span prolonging effect in females than in males.
Animals ; Antioxidants ; isolation & purification ; pharmacology ; Bignoniaceae ; chemistry ; Drosophila melanogaster ; drug effects ; Female ; Lipid Peroxidation ; drug effects ; Longevity ; drug effects ; Male ; Phenols ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; pharmacology ; Plant Roots ; chemistry ; Sex Factors

OBJECTIVE: To investigate the effect of linear alkylbenzenesulfonate (LAS) on the reproductive capacity and life-span of Drosophila melanogaster. METHODS: Drosophila melanogaster images within 8 h after eclosion were collected with ether anesthesia. The female and male of similar size and normal shape and behavior were selected. The Drosophila melanogasters were cultured in the culture medium containing LAS of different densities. We divided the Drosophila melanogaster into 4 groups according to LAS concentrations: a low dose group with LAS 150 mg/kg, a middle dose group with LAS 300 mg/kg,a high dose group with LAS 600 mg/kg, and a control group without LAS, respectively. The changes of the reproductive capacity, median lethal time, mean life-span and max mean life-span of drosophila melanogaster with different doses of LAS were measured and compared with those of the control. RESULTS: The pupa numbers of filial generation of Drosophila melanogaster in the low, middle, and high dose groups (85.07%, 84.59% and 71.88%, respectively) were lower than those in the control group (P<0.01). The median lethal time, mean life-span and max mean life-span of Drosophila melanogaster in the low, middle, and high dose groups were shorter than those in the control group (P<0.05). The change of life-span of Drosophila melanogaster in the high dose group was remarkable: the median lethal time of female and male shortened 13 days and 15 days, the mean life-span of female and male shortened 18 days and 14 days, and the max mean life-span of female and male shortened 14 days and 12 days, respectively. CONCLUSION LAS has definite toxicity to Drosophila melanogaster, which can degrade the reproductive capacity of Drosophila melanogaster and shorten the life-span of Drosophila melanogaster.
Alkanesulfonic Acids ; pharmacology ; toxicity ; Animals ; Dose-Response Relationship, Drug ; Drosophila melanogaster ; physiology ; Female ; Life Expectancy ; Longevity ; Male ; Reproduction ; drug effects ; Surface-Active Agents ; pharmacology ; toxicity

OBJECTIVETo explore the expression changes of age-related genes in different stages of aging and the regulating effects of Chuanxiong extract on it.

METHODAccording to the different stages of aging, the experiments were tested at two time points of 2 d and 6 d. Using realtime RT-PCR (qRT-PCR) to test the expression change of aging-related genes among the groups.

RESULTCompared with the 2 d control group, the expression of age-1, daf-2, let-363 were up-regulated in the 6 d control group (P < 0.05) while the expression of ins-18, let-60, sir-2.1, sod-3 were down-regulated (P < 0.05). Compared with the 2 d administration group, the expression of age-1, daf-2, let-363 were significantly up-regulated (P < 0.01) in the 6 d administration group after treated with CXE while the expression of ins-18, let-60, sir-2.1, sod-3 were significantly down-regulated (P < 0.01).

CONCLUSIONIn the progress of aging, the expression of age-1, daf-2, let-363 increased, functioning as aging-promoting genes; while the expression of ins-18, let-60, sir-2.1, sod-3 decreased, functioning as longevity genes; CXE extended the lifespan through inhibiting the expression of these aging-promoting genes and increasing the expression of longevity genes, which would be the molecular mechaniSm of anti-aging of traditional Chinese medicine that can promote Qi and activate blood.

Animals ; Caenorhabditis elegans ; genetics ; growth & development ; metabolism ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Developmental ; drug effects ; Longevity ; drug effects

OBJECTIVETo explore the effect of Ligusticam chuanxiong extract (CXE) on lifespan of Caenorhabditis elegans and investigate its underlyirig molecular mechanisms.

METHODThe lifespan assay was carried out on animals grouped into blank control group and CXE groups with concentration from low to high: 12.5, 25, 50, 100 mg x L(-1) by examining the effect of CXE on mean lifespan and maximum lifespan of C. elegans. According to the result of lifespan assay, we cultured the animals with the optimal concentration of CXE for 10 days, and tested the expression change of aging-related genes between the control and CXE group by realtime RT-PCR (qRT-PCR).

RESULTCompared with the control, 25, 50, 100 mg x L(-1) CXE all significantly extended the mean lifespan (15.7%, 9.1%, 6.2% respectively) and the maximum lifespan (15.0%, 6.8%, 6.6% respectively) of C. elegans. After treatment with 25 mg x L(-1) CXE the expression of hsp-70, skn-1 were obviously up-regulated while the expression of akt-2, tub-1 were significantly down-regulated.

CONCLUSIONCXE significantly extend the lifespan of C. elegans, and the underlying molecular mechanism is related with genes of Insulin/IGF-1 signaling pathway and dietary restriction system.

Animals ; Caenorhabditis elegans ; drug effects ; genetics ; physiology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gene Expression Regulation ; drug effects ; Longevity ; drug effects ; genetics

OBJECTIVETo investigate effect of Epimedium flavonoids (EF), positively controlled by caloric restriction (CR) method, in retarding aging of the model organism C. elegans, in order to establish a basis for studying its action mechanism.

METHODSExperiment for life-time analysis was conducted on animals grouped into the blank group, the CR group, and the high and low dose EF groups to observe their mean lifespan, maximum lifespan and age-dependent mortality. And the reproductive capacity test and acute heat-stress analysis were carried out in the blank group and the high dose EF group to observe the subalgebra and the mean survival time under acute heat-stress at 35 degrees C.

RESULTSAs compared with the blank group, the mean lifespan in the two EF group and the maximum lifespan in the high dose EF group were higher, and the age-dependent mortality in the high dose EF group was lower significantly (P<0.05 or P<0.01); as compared with the CR group, the mean lifespan and maximum lifespan in the high dose EF group were higher (P<0.01); but no significant difference of the subalgebra between the blank group and the high dose EF group was shown (P>0.05). Compared with the blank group, the mean lifespan in the high dose EF group was significantly prolonged under acute heat-stress at 35 degrees C (P<0.01).

CONCLUSIONEF can retard the aging of C. elegans without damage on the reproductive capacity, and significantly improve its capacity against acute heat-stress.

Aging ; drug effects ; physiology ; Animals ; Caenorhabditis elegans ; drug effects ; physiology ; Dose-Response Relationship, Drug ; Epimedium ; chemistry ; Female ; Flavonoids ; pharmacology ; Hot Temperature ; adverse effects ; Longevity ; drug effects ; physiology ; Male ; Reproduction ; drug effects ; Stress, Physiological ; drug effects

OBJECTIVETo observe the effects of diethlhexyl phthalate (DEHP) on lipid peroxidation and the life span in Drosophila melanogaster.

METHODSFed Drosophila with the concentration 0.20% DEHP of exposure after 0, 14, 28 days, the activity of total superoxide dismutase (SOD), CuZn-SOD and the concentration of malondialdehyde were determined. At the same time, the longevity test was carried out to examine the effect of DEHP on the Drosophila's lifespan.

RESULTSThe lifespan of Drosophila was shortened in a dose of DEHP exposed groups. The indexes of mean life span (MLS), 50% lethal time and mean maximum life span in three DEHP-treated groups (concentration of 0.05%, 0.10% and 0.20%) were lower than those of the controlled group respectively (P < 0.01 or P < 0.05). The MLS of both Drosophila sexes were reduced from the control of 64 days and 59 days to the test 60 days-52 days and 54 days-49 days respectively. DEHP decreased the activity of SOD (P < 0.01 or P < 0.05), and lead to a time-dependent relation and an increase in the concentration of malondialdehyde (P < 0.01 or P < 0.05) in the DEHP-exposed Drosophila groups.

CONCLUSIONDEHP might promote the process of lipid peroxidation and shorten the life span in Drosophila melanogaster. It should be one of the reasons in the senescence of Drosophila.

Animals ; Diethylhexyl Phthalate ; pharmacology ; Drosophila melanogaster ; drug effects ; growth & development ; metabolism ; Female ; Lipid Peroxidation ; drug effects ; Longevity ; drug effects ; Male ; Malondialdehyde ; metabolism ; Superoxide Dismutase ; metabolism ; Time Factors