Bioactive Nutrients and Nutrigenomics in Age-Related Diseases.

The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the "omics" technologies (transcriptomics, proteomics and metabolomics) are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

Cooperation of docosahexaenoic acid and vitamin E in the regulation of UDP-glucuronosyltransferase mRNA expression.

Docosahexaenoic acid (DHA) is a well known chemopreventive nutrient within diet formulations, but it may also exert toxic effects on cultured cells, while this is limited when also another relevant nutrient as vitamin E is present. This effect, beside the involvement of the two nutrients in oxidative processes, likely affects the expression of specific genes. To obtain information on combined activities of DHA and vitamin E on some gene products previously resulted to be in vivo regulated from dietary unsaturated fats, the effect of the two nutrients was evaluated in human cell line HepG2. Independently, DHA and vitamin E resulted to affect only slightly UDP-glucuronosyltransferase 1A1 (UGT1A1) mRNA expression. Nevertheless, their combination produced a considerable reduction of this mRNA. DHA also downregulated stearoyl-CoA desaturase (SCD) and sterol regulatory element binding protein (SREBP-1) expression, while vitamin E did not affect these products. However, their combination abolished the downregulation of SCD but did not affect that of SREBP-1. Therefore the effect of the two nutrients is related to specific gene regulation processes resulting in a cooperation which might be related to their physiological effects as dietary components.

Protective and Restorative Effects of Nutrients and Phytochemicals.

INTORODUCTION: Dietary intake fundamentally provides reintegration of energy and essential nutrients to human organisms. However, its qualitative and quantitative composition strongly affects individual's health, possibly being either a preventive or a risk factor. It was shown that nutritional status resulting from long-term exposition to specific diet formulations can outstandingly reduce incidences of most common and most important diseases of the developed world, such as cardiovascular and neoplastic diseases. Diet formulations result from different food combinations which bring specific nutrient molecules. Numerous molecules, mostly but not exclusively from vegetal foods, have been characterized among nutritional components as being particularly responsible for diet capabilities to exert risk reduction. These "bioactive nutrients" are able to produce effects which go beyond basic reintegration tasks, i.e. energetic and/or structural, but are specifically pharmacologically active within pathophysiological pathways related to many diseases, being able to selectively affect processes such as cell proliferation, apoptosis, inflammation, differentiation, angiogenesis, DNA repair and carcinogens activation. CONCLUSION: The present review was aimed to know the molecular mechanisms and pathways of activity of bioactive molecules; which will firstly allow search for optimal food composition and intake, and then use them as possible therapeutical targets and/or diagnostics. Also, the present review discussed the therapeutic effect of both nutrients and phytochemicals.

Effect of unsaturated fat intake from Mediterranean diet on rat liver mRNA expression profile: selective modulation of genes involved in lipid metabolism.

BACKGROUND AND AIM: The lipid content of Mediterranean diet is mostly accounted for its disease preventive action. We investigated whether the short term nutritional effect of a fat quota mainly derived from olive and fish oil affects liver mRNA expression profile in rats. METHODS AND RESULTS: The study was carried out using DNA microarray techniques. The effect was evaluated at liver mRNA expression level to identify genes whose expression was regulated by dietary modifications. Two groups of six rats were alternatively supplied for two weeks with either a control or with an experimental diet. Both diets were semisynthetic and isocaloric, with identical major nutrients composition (protein 20%, carbohydrates 56% and lipids 22% of total energy) being different only in the quality of fats. The lipid quota of the control diet contained exclusively saturated animal fats, derived from butter, while in the experimental diet some unsaturated fats were present, being derived also from olive and fish oil (10% and 6% of total energy, respectively). Out of 26,334 genes analyzed, 11,292 were found expressed in the liver, 72 were induced and 180 were inhibited from the experimental diet. Out of these, 33 of the induced and 59 of the inhibited species have a well known function. CONCLUSIONS: The diet with olive and fish oil modulates several genes related to lipolysis or lipogenesis and newly identified responders from other metabolisms. Some of these genes are also reported to be similarly modulated by the action of fibrates, but without the complete gene activation typical of these PPARalpha ligands.