OBJECTIVE: To investigate the changes of lipid metabolism and stress response of adult C.elegans exposed to non-freezing low temperature and explore the possible mechanism. METHODS: The survival rate and activity of adult C.elegans cultured at 20℃ or 4℃ were observed.Lipid metabolism of the cultured adult C.elegans was evaluated using oil red O staining and by detecting the expressions of the genes related with lipid metabolism.The effects of low temperature exposure on stress level of adult C.elegans were evaluated using mitochondrial fluorescence staining and by detecting the expression levels of stress-related genes and antioxidant genes at both the mRNA and protein levels. RESULTS: The lifespan and activity of adult C.elegans exposed to low temperature were significantly reduced with decreased lipid accumulation (P < 0.05) and decreased expressions of genes related with fatty acid synthesis and metabolism (fat-5, fat-6, fat-7, fasn-1, nhr-49, acs-2 and aco-1;P < 0.01).Cold stress significantly increased the expressions of heat shock proteins hsp-70 and hsp16.2(P < 0.05) but lowered the number of mitochondria (P < 0.0001) and the expressions of atfs-1, sod-2, sod-3 and gpx-1(P < 0.05).Knockout of fat-5, nhr-49 or both fat-5 and fat-6 obviously enhanced the sensitivity of C.elegans to cold stress as shown by further reduced activity (P < 0.05) and reduced survival rate at 24 h (P < 0.0001) under cold stress. CONCLUSION Exposure to a low temperature at 4℃ results in lowered lipid metabolism of adult C.elegans accompanied by a decreased mitochondrial number and quality control ability, which triggers high expressions of stress-related genes and causes reduction of antioxidant capacity, thus callsing lowered activity and reduced lifespan of C.elegans.
Animals ; Antioxidants/metabolism* ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/genetics* ; Cold-Shock Response ; Lipid Metabolism ; Lipid Metabolism Disorders ; Longevity/genetics*

Microbial cell factories capable of producing valuable chemicals from renewable feedstocks provide a promising alternative towards sustainability. However, environmental stress remarkably affects the performance of microbial cell factories. By extending the chronological lifespan of microbial cells, the performance of microbial cell factories can be greatly improved. Firstly, an evaluation system for chronological lifespan and semi-chronological lifespan was established based on the changes in survival rates. Secondly, the addition of anti-aging drugs such as cysteine, carnosine, aminoguanidine and glucosamine increased the chronological lifespan of E. coli by 80%, 80%, 50% and 120%, respectively. Finally, we demonstrated that extending the chronological lifespan of E. coli increased the yield of metabolites produced by E. coli cell factories with endogenous (lactic acid and pyruvic acid) or exogenous (malic acid) metabolic pathway by 30.0%, 25.0%, and 27.0%, respectively. The strategy of extending chronological lifespan of E. coli provides a potential approach for enhancing the performance of microbial cell factories.
Escherichia coli/genetics* ; Lactic Acid ; Longevity ; Metabolic Engineering ; Metabolic Networks and Pathways

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

Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.
Animals ; Caenorhabditis elegans ; genetics ; metabolism ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; Female ; Lipid Droplets ; metabolism ; Lipid Metabolism ; physiology ; Longevity ; physiology ; Mutation ; Oogenesis ; physiology

Aging ; genetics ; metabolism ; Animals ; Diabetes Mellitus ; enzymology ; metabolism ; Humans ; Longevity ; genetics ; physiology ; Neoplasms ; enzymology ; metabolism ; Neurodegenerative Diseases ; enzymology ; metabolism ; Obesity ; enzymology ; metabolism ; Sirtuins ; genetics ; metabolism

The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD(+)-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in promoting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.
Aging, Premature ; enzymology ; genetics ; Animals ; Humans ; Longevity ; genetics ; Sirtuin 1 ; genetics ; metabolism

The p66Shc gene has emerged as a novel gerontogene affecting health and life during aging. In murine models of aging,a genetic deficiency of the p66Shc gene,which encodes a phosphotyrosine signal adapter protein,extends life span by 30%. p66Shc is a crucial regulator of reactive oxygen species levels and is involved in age-related dysfunctions. UP to now,oxidative stress has been recognized to be involved in human diseases such as high cholesterol,diabetes,and cardiovascular diseases. Further study on the role of p66Shc will facilitate the research of novel disease-targetted drugs and slow down or cure age-related pathologies.
Aging ; genetics ; Animals ; Humans ; Longevity ; genetics ; Mice ; Oxidative Stress ; physiology ; Reactive Oxygen Species ; metabolism ; Shc Signaling Adaptor Proteins ; genetics

OBJECTIVETo assess the association between SIRT1 gene polymorphisms and the longevity phenomena in Yongfu region of Guangxi. In this case-control study, 500 individuals from Yongfu region of Guangxi were recruited. The subjects were divided into a longevity group (n=223, average age=93.17 U+00B1 3.08 yr) and a healthy control group (n=277, average age=46.92 U+00B1 17.12 yr). Polymerase chain reaction-high resolution melting curve (PCR-HRM) and DNA sequencing were used to determine the allelic and genotypic frequencies of rs3758391, rs3740051, rs2273773, rs4746720 and rs10997870 polymorphisms of SIRT1 gene in the two groups. The association between above polymorphisms and longevity was assessed.

RESULTSIn the longevity group, CT genotype of the rs4746720 locus was significantly more common than CC and TT genotypes (P=0.000, OR=2.098, 95%CI:1.412-4.117). However, no significant difference was found in the allelic and genotypic frequencies of rs3758391, rs3740051 and rs2273773 between the two groups.

CONCLUSIONThere is an association between rs4746720 of SIRT1 gene and longevity in Yongfu region of Guangxi.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; China ; Female ; Gene Frequency ; Gene Order ; Genetic Association Studies ; Genotype ; Humans ; Longevity ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Sirtuin 1 ; genetics ; Young Adult

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