A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.     

Vanadate enhances insulin-receptor binding in gestational diabetic human placenta

Although vanadium is found abundantly in animal and plant kingdoms its biological effects are not clear. Vanadate compounds have been shown to normalize blood glucose levels in streptozotocin treated rats, enhance glucose oxidation and improve the sensitivity to insulin by enhanced receptor binding in rat adipocytes. The aim of the present study was to investigate the effect of vanadate, at high (0–8 mmol l^?1) and low (0–1·0 mmol l^?1) physiological concentrations, on [¹²⁵I]-insulin binding in the placenta of three groups of pateints, namely from normal (N) controls, gestational diabetics (GDM) and women with risk factors in their medical history for developing diabetes mellitus (RF). Vanadate at low concentrations (0·2–0·6 mmol l^?1) enhanced the maximal binding 2-fold in GDM placenta but only increased (up to 1·2-fold) the binding slightly at high cncentrations (5 mmol l^?1). However with placenta from normal or women at risk, vanadate increased the [¹²⁵I]-insulin binding up to 1·2-fold both at low and high concentrations. Thus it appears that vanadate augements insulin binding in the placenta from women with gestational diabetes mellitus.     

向日葵花盘功能成分及研究现状

向日葵(Helianthus annuus L.)作为我国重要的油料作物之一,其葵花籽油的提取已经实现工业化生产,但其副产物向日葵盘、秸秆、葵花籽壳和饼粕等仍然利用不足.随着技术设备条件的优化及产业化条件的成熟,向日葵副产物具有十分广阔的开发应用前景.本文对向日葵花盘现阶段的综合利用情况进行介绍,并总结了向日葵花盘中绿原酸、水溶性多糖、萜类化合物等重要活性物质的提取方法.针对我国目前面临的向日葵作物综合利用发展中出现的向日葵花盘副产物处理难问题,阐述了向日葵花盘的药用价值及其重新开发和综合利用的方法,为向日葵花盘的利用提供指导.     

Toolbox: Creating a systematic database of secretory pathway proteins uncovers new cargo for COPI

A third of yeast genes encode for proteins that function in the endomembrane system. However, the precise localization for many of these proteins is still uncertain. Here, we visualized a collection of ~500 N‐terminally, green fluorescent protein (GFP), tagged proteins of the yeast Saccharomyces cerevisiae. By co‐localizing them with 7 known markers of endomembrane compartments we determined the localization for over 200 of them. Using this approach, we create a systematic database of the various secretory compartments and identify several new residents. Focusing in, we now suggest that Lam5 resides in contact sites between the endoplasmic reticulum and the late Golgi. Additionally, analysis of interactions between the COPI coat and co‐localizing proteins from our screen identifies a subset of proteins that are COPI‐cargo. In summary, our approach defines the protein roster within each compartment enabling characterization of the physical and functional organization of the endomembrane system and its components.      

Stress granules counteract senescence by sequestration of PAI‐1

Cellular senescence is a physiological response by which an organism halts the proliferation of potentially harmful and damaged cells. However, the accumulation of senescent cells over time can become deleterious leading to diseases and physiological decline. Our data reveal a novel interplay between senescence and the stress response that affects both the progression of senescence and the behavior of senescent cells. We show that constitutive exposure to stress induces the formation of stress granules (SGs) in proliferative and presenescent cells, but not in fully senescent cells. Stress granule assembly alone is sufficient to decrease the number of senescent cells without affecting the expression of bona fide senescence markers. SG‐mediated inhibition of senescence is associated with the recruitment of the plasminogen activator inhibitor‐1 (PAI‐1), a known promoter of senescence, to these entities. PAI‐1 localization to SGs increases the translocation of cyclin D1 to the nucleus, promotes RB phosphorylation, and maintains a proliferative, non‐senescent state. Together, our data indicate that SGs may be targets of intervention to modulate senescence in order to impair or prevent its deleterious effects.     

Genetic Aspects of Myoclonus–Dystonia Syndrome (MDS)

Myoclonus–dystonia (M–D) is an autosomal-dominant movement disorder with onset in the first two decades of life. Mutations in the epsilon-sarcoglycan gene (SGCE, DYT11) on chromosome 7q21–q31 represent the major genetic cause of M–D in some populations. The syndrome was related with mutations in two other genes (DRD2 and DYT1). A second locus has been reported in one large M–D family (DYT15, 18p11), but no gene has been identified yet. In this review, we discuss genetic aspects of myoclonus–dystonia.