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 silent information regulator protein 2 (Sir2) and its homologues play an important role in the regulation of cellular physiological processes such as survival, apoptosis, and aging. SIRT1, the mammalian Sir 2 homologue, has been shown to deacetylate a wide range of non-histone substrates and histone substrates. It has been constantly reported that SIRT1 may be associated with the occurrence of metabolic syndrome, genomic homeostasis, tumors, and neurodegenerative diseases. Calorie restriction may mitigate many major diseases in rodent models by SIRT1-mediated deacetylase activity and prolong the life expectancies in these animals. Therefore, SIRT1 may be emphasized as a new therapy target for many different diseases.
Animals ; Caloric Restriction ; Humans ; Longevity ; Sirtuin 1 ; genetics ; physiology ; Substrate Specificity

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 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

Animals ; Apoptosis ; genetics ; Gene Expression Regulation ; Humans ; Longevity ; genetics ; Medicine, Chinese Traditional ; Neoplasms ; genetics ; Rats ; T-Lymphocytes ; cytology

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*

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Animals ; Energy Metabolism ; genetics ; Growth Hormone ; metabolism ; Humans ; Insulin ; metabolism ; Longevity ; genetics ; Metabolism ; genetics ; Signal Transduction ; genetics

OBJECTIVETo explore the relationship between Shen-deficiency syndrome (SDS) and the insert/deficit (I/D) polymorphism types (PMTs) of angiotensin converting enzyme (ACE) gene in longevous elders in Bama area of Guangxi municipality.

METHODSThe investigation on 27 centenarians (Group A), 56 elders of 90-99 years old (Group B) and 114 of 60-89 years old (Group C) was carried out by questionnaire, and the polymorphism was detected using polymerize chain reaction detection, single strand conformation polymorphism (SSCP) analysis, and direct sequencing technique. And the study was controlled by 79 naturally died elders within 60-70 years old.

RESULTSThe presenting frequencies of SDS in various PMT were D/D, I/D and I/I in rising order. The frequencies of PMT, I/I, I/D and D/D, were 37.04% (10/27), 33.33% (9/27), and 29.63% (8/27) respectively; the frequency rates of I and D alleles were 53.70% (29/54) and 46.30% (25/54) in Group A. Comparison of frequency of D/D and D allele between groups showed that Group A was significantly different to Group C (P<0.05) and also to the control (P<0.01), while all the frequencies in Group A and B were rather identical, showing insignificant difference (P>0.05). SSCP analysis showed no significant difference in D/D among groups. Outcomes of direct sequencing test further proved the correctness of I/D ACE polymorphism detection.

CONCLUSIONSDS is closely correlated with ACE gene polymorphism and life span. Whereas, other multiple factors that influence longevity should also be taken into consideration.

Aged ; Aged, 80 and over ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Genome, Human ; Genotype ; Humans ; Longevity ; genetics ; Medicine, Chinese Traditional ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic

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

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