Natural antioxidants in prevention of accelerated ageing: a departure from conventional paradigms required.

The modern lifestyle is characterised by various factors that cause accelerating ageing by the upregulation of oxidative stress and inflammation-two processes that are inextricably linked in an endless circle of self-propagation. Inflammation in particular is commonly accepted as aetiological factor in many chronic disease states, such as obesity, diabetes and depression. In terms of disease prevention or treatment, interventions aimed at changing dietary and/or exercise habits have had limited success in practise, mostly due to poor long-term compliance. Furthermore, other primary stimuli responsible for eliciting an oxidative stress or inflammatory response-e.g. psychological stress and anxiety-cannot always be easily addressed. Thus, preventive medicine aimed at countering the oxidative stress and/or inflammatory responses has become of interest. Especially in developing countries, such as South Africa, the option of development of effective strategies from plants warrants further investigation. A brief overview of the most relevant and promising South African plants which have been identified in the context of inflammation, oxidative stress and chronic disease is provided here. In addition, and more specifically, our group and others have shown considerable beneficial effects across many models, after treatment with products derived from grapes. Of particular interest, specific cellular mechanisms have been identified as therapeutic targets of grape-derived polyphenols in the context of inflammation and oxidative stress. The depth of these studies afforded some additional insights, related to methodological considerations pertaining to animal vs. human models in natural product research, which may address the current tendency for generally poor translation of positive animal model results into human in vivo models. The importance of considering individual data vs. group averages in this context is highlighted.

[Modern approaches to correction and prophylaxis of premature aging using adaptogenes of plant origin].

Last years, the big attention is given studying of the methods promoting increase of the immune status of an organism, got under influence of extreme factors, in particular, ionas radiations. In this connection perspectivity of application of laboratory diagnostics for testing a degree of defeat of immune system and application phytoadaptogenes is proved, namely: tinctures of a Panacis ginseng, Schizandrae chinensis, an extract Elaetherococcus for correction of such conditions.

Murine models of premature ageing for the study of diet-induced immune changes: improvement of leucocyte functions in two strains of old prematurely ageing mice by dietary supplementation with sulphur-containing antioxidants.

Several immune functions are markers of health, biological age and predictors of longevity. A chronic oxidative and inflammatory state is the main cause of ageing and the immune system is involved in the rate of ageing. Thus, several murine models of premature ageing have been proposed owing to their early immunosenescence and oxidative stress, such as ovariectomised rats and mice, obese rats and anxious mice. In the last model, the most extensively studied by us, mice showing anxiety have an aged immune function and redox status as well as a shorter longevity in comparison with animals without anxiety of the same chronological age, being denominated prematurely ageing mice. A confirmation of the above is that the administration of diets supplemented with antioxidants improves the redox status and immune functions and increases the longevity of prematurely ageing mice. Antioxidant precursors of glutathione such as thioproline or N-acetylcysteine, which have a relevant role in ageing, have been the most widely investigated in adult prematurely ageing mice in our laboratory. In the present work, we have studied the effects of the ingestion for 5 weeks of a diet supplemented with 0·1% (w/w) thioproline+N-acetylcysteine on several functions of leucocytes from chronological old (69-73 weeks of age) prematurely ageing mice of two strains (Swiss and BALB/c). The results show an improvement of the immune functions, with their values becoming closer to those in adult animals (24±2 weeks). Thus, an adequate nutrition with antioxidants, even in aged subjects, could be a good strategy to retard ageing.

Omega-3 polyunsaturated fatty acids ameliorate the severity of ileitis in the senescence accelerated mice (SAM)P1/Yit mice model.

Clinical studies using omega-3 polyunsaturated fatty acids (omega3-PUFA) to Crohn's disease (CD) are conflicting. Beneficial effects of dietary omega3-PUFA intake in various experimental inflammatory bowel disease (IBD) models have been reported. However, animal models of large intestinal inflammation have been used in all previous studies, and the effect of omega3 fat in an animal model of small intestinal inflammation has not been reported. We hypothesized that the effects of omega3 fat are different between large and small intestine. The aim of this study was to determine whether the direct effect of omega3 fat is beneficial for small intestinal inflammation. Senescence accelerated mice (SAM)P1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. The numbers of F4/80-positive monocyte-macrophage cells as well as beta7-integrin-positive lymphocytes in the intestinal mucosa were increased significantly compared with those in the control mice (AKR-J mice). The area of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-positive vessels was also increased. The degree of expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and interferon (IFN)-gamma mRNA were increased significantly compared with those in the control mice. The feeding of two different kinds of omega3 fat (fish-oil-rich and perilla-oil-rich diets) for 16 weeks to SAMP1/Yit mice ameliorated inflammation of the terminal ileum significantly. In both the omega3-fat-rich diet groups, enhanced infiltration of F4/80-positive monocytes/macrophages in intestinal mucosa of SAMP1/Yit mice cells and the increased levels of MCP-1, IL-6 and IFN-gamma mRNA expression were ameliorated significantly compared with those in the control diet group. The results suggest that omega3 fat is beneficial for small intestinal inflammation by inhibition of monocyte recruitment to inflamed intestinal mucosa.

A diet supplemented with thiolic anti-oxidants improves leucocyte function in two strains of prematurely ageing mice.

1. According to previous studies, Swiss mice of the same age showed striking interindividual differences in behaviour when exposed to a T-maze test, with a slow performance being linked to an impaired immune function, hyperemotional response to stress and a shorter life span compared with mice that quickly explore the maze. These facts led us to propose the slow mice as a model of prematurely ageing mice (PAM). 2. In the present study, we investigated whether this prematurely ageing model could be found in other strains of mice, such as BALB/c mice, by analysing several lymphocytes functions, such as adherence, chemotaxis, proliferative response to the mitogen concanavalin A (Con A), interleukin (IL)-2 release and natural killer (NK) activity. In addition, we tested the probable beneficial effects on these functions of dietary supplementation with thioproline (TP) plus N-acetylcysteine (NAC; 0.1% w/w of each anti-oxidant) in female Swiss and BALB/c mice. 3. Our model of premature ageing, previously reported in Swiss mice, has also been reproduced in the inbred BALB/c mouse strain, in which PAM showing an immunosenescence in several lymphocyte functions, such as lower chemotaxis, proliferative response to Con A, IL-2 release and NK activity, as well as higher adherence, were observed. A short-term (5 week) ingestion of TP + NAC by female Swiss and BALB/c mice improved leucocyte function, increasing chemotaxis, the proliferative response to Con A, IL-2 release and NK activity and decreasing the adherence of lymphocytes. These effects are greatest in cells from PAM of both strains. 4. In conclusion, our model of premature ageing has been reproduced in an inbred strain. In addition, the ingestion of a diet supplemented with two thiolic anti-oxidants, such as NAC and TP, has been shown to be beneficial to the immune response in PAM.