Development of liver fibrosis during aging: effects of caloric restriction.

Liver is the central metabolic organ of the body and diet is considered one of the main environmental factors that can impact on aging liver. In the elderly stage liver function is relatively well conserved although there are a variety of not well defined morphological changes related to liver fibrosis which is commonly associated with an inflammatory state. The aim of this paper is to study these alterations during the physiological process of aging in Wistar rats and also test if caloric restriction (CR) could ameliorate them. As fibrosis is associated to hepatic stellate cell (HSC) function we also analyzed these cells during aging. Livers from five groups of male Wistar rats (3-, 8-, 24-months old ad libitum and 8- and 24-months caloric restricted rats) were used in this study. Histological analysis, expression of genes implicated in liver fibrosis and the status of inflammatory step-pathways as p38 mitogen-activated protein kinase (p38-MAPK), c-Jun N-terminal kinase (JNK) and the nuclear factor kappa B (NFkB) isoforms, p50 and p65, in cytosolic and nuclear fractions were performed. During elderly, associated with morphological change of HSC, there is a progressive increase in collagen deposition due to an inhibition in collagen degradation. Higher expression of cytokines and the activation of inflammatory pathways are associated with aging. CR ameliorates these circumstances being more effective when it started in middle age. In conclusion elderly stage is associated to a mild fibrotic and inflammatory state in the liver which could be ameliorated after CR.

Analysis of the -1438 G/A polymorphism of the 5-HT2A serotonin receptor gene in bulimia nervosa patients with or without a history of anorexia nervosa.

A single nucleotide polymorphism (-1438 G/A) located 1438 base pairs upstream of the consensus start site of the 5-HT2A receptor gene has been reported. The hypothesis that this gene polymorphism may be a susceptibility factor in bulimia nervosa was explored in a female population of purgative bulimics. Bulimia nervosa patients who have suffered preceding anorexia nervosa episodes formed the so-called previous anorexia nervosa bulimic patient group. At variance with some previous reports, when the frequency distribution of genotypes and alleles was compared in patients and controls, no differences were detected regardless of whether the bulimia nervosa patients had suffered prior anorexia nervosa episodes.

Polymorphisms within the promoter and the intron 2 of the serotonin transporter gene in a population of bulimic patients.

The serotonin transporter (5-HTT) gene is a firm candidate to explain eating disorders. In this association study, two different polymorphisms were analysed: a variable number of tandem repeat (VNTR) polymorphism in intron 2 and a deletion/insertion polymorphism (5-HTTLPR) in the promoter region. The hypothesis that these gene polymorphisms may be a susceptibility factor in bulimia nervosa (BN) was explored in a female population of 102 purgative bulimics. BN patients who have suffered preceding anorexia nervosa (AN) episodes formed the so-called previous AN bulimic patient group. In our sample of normal-eater controls and purging type bulimics, regardless of whether or not the BN patients had suffered prior AN episodes, no differences were found considering the frequencies of genotypes, alleles or haplotypes of both polymorphic regions of the 5-HTT gene.