Dietary vitamin E (VE) is known to regulate gene expression by altering mRNA concentrations. Recently, micro-RNA (miRNA) have been discovered as a means of posttranscriptional gene regulation. Since the effect of VE on miRNA regulation is unknown, we fed rats for 6 months diets deficient or sufficient in VE and determined hepatic concentrations of miRNA involved in processes previously associated with VE (lipid metabolism, miRNA-122a; cancer and inflammation, miRNA-125b). VE-deficiency resulted in reduced concentrations of miRNA-122a and miRNA-125b. The findings of the present study demonstrate that differences in dietary VE may affect hepatic miRNA concentrations in vivo.

Whole grains are known to influence postprandial glucose response and insulin demand and are inversely associated with diabetes risk. Genetic variation of the transcription factor-7-like 2 encoding gene (TCF7L2) is assumed to promote an early insulin secretory defect and has been consistently attributed to the risk of developing type 2 diabetes. The present study examined the hypothesis that the protective effect of whole grains might be attenuated in the presence of the rs7903146 risk-conferring T-allele. We employed a case -cohort study of 2318 randomised individuals and 724 incident type 2 diabetes cases from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Multivariate Cox regression was used to estimate relative risks of diabetes including product terms testing for the genotype-specific effect modification of dietary whole grain. Dietary intake of whole grains was assessed by a validated FFQ. The TCF7L2 rs7903146 T-allele was associated with type 2 diabetes (hazard ratio ¼ 1·51; 95 % CI 1·21, 1·87) and modified the inverse association between whole-grain intake and diabetes risk (P¼ 0·016 for interaction). While whole-grain intake was inversely associated with diabetes risk among rs7903146 CC homozygote carriers (hazard ratio for 50 g portion per d ¼ 0·86; 95 % CI 0·75, 0·99), the T-allele negated the protective effect of whole-grain intake (hazard ratio among T-allele carriers for 50 g portion per d ¼ 1·08; 95 % CI 0·96, 1·23). These data provide evidence that the beneficial effect of whole-grain intake on diabetes risk is modified by TCF7L2 rs7903146.

Lifespan in Caenorhabditis elegans, Drosophila, and mice is regulated by conserved signaling networks, including the insulin/insulinlike growth factor 1 (IGF-1) signaling cascade and pathways depending on sirtuins, a family of NAD + -dependent deacetylases. Small molecules such as resveratrol are of great interest because they increase lifespan in many species in a sirtuin-dependent manner. However, no endogenous small molecules that regulate lifespan via sirtuins have been identified, and the mechanisms underlying sirtuin-dependent longevity are not well understood. Here, we show that in C. elegans, two endogenously produced small molecules, the dauer-inducing ascarosides ascr#2 and ascr#3, regulate lifespan and stress resistance through chemosensory pathways and the sirtuin SIR-2.1. Ascarosides extend adult lifespan and stress resistance without reducing fecundity or feeding rate, and these effects are reduced or abolished when nutrients are restricted. We found that ascaroside-mediated longevity is fully abolished by loss of SIR-2.1 and that the effect of ascr#2 requires expression of the G protein-coupled receptor DAF-37 in specific chemosensory neurons. In contrast to many other lifespan-modulating factors, ascarosidemediated lifespan increases do not require insulin signaling via the FOXO homolog DAF-16 or the insulin/IGF-1-receptor homolog DAF-2. Our study demonstrates that C. elegans produces specific small molecules to control adult lifespan in a sirtuin-dependent manner, supporting the hypothesis that endogenous regulation of metazoan lifespan functions, in part, via sirtuins. These findings strengthen the link between chemosensory inputs and conserved mechanisms of lifespan regulation in metazoans and suggest a model for communal lifespan regulation in C. elegans.aging | chemosensation | β oxidation | ecology

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