Keynotes
Genistein consumption does not increase lifespan, but it improves healthspan under stress conditions
by Consuelo Borras
Abstract
Genistein is a phytoestrogen which is extensively used in clinical practice, for instance to prevent menopause-associated hot flushes, as it can mimics some of the beneficial effects of estrogens and is devoid of significant side effects. It is present in soya in significant amounts and previous results of our group and others have shown that soya consumption can decrease oxidative stress and improve cardiovascular function in rats. In this study, we performed a controlled lifelong study with male OF1 mice consuming either a soya-free diet or a soya-rich diet. We found that, despite we found an increase in the expression and activity of antioxidant enzymes in soya consuming mice, it didn’t increase lifespan. We reasoned that soya diet was not able to increase lifespan in a very healthy population, but perhaps it could extend lifespan in stressed animals such as type 2 diabetic Goto Kakazaki rats. Indeed, this was the case, we found that rats consuming a soy rich diet developed the disease at a lower rate, showed lower oxidative stress and better metabolic profile, and therefore lived longer than soy-free diet consuming rats.
Keynotes
Modelling Polyphenol-Protein Interactions
by Stephen R. Euston
Abstract
The interaction between proteins and polyphenols is known to modify both the bioavailability and bioactivity of dietary polyphenols. Understanding these interactions can facilitate the design of delivery systems for polyphenols in the digestive tract. Molecular modelling of protein-polyphenol and protein-ligand interactions in general has long been used as a way to identify mall mole ule biding sites on proteins. However, these are often used without a careful consideration of the assumptions used and limitations of these methods, and how this affects the accuracy of the predictions. In this talk, two common methods for predicting binding site location and binding energy, molecular dynamics simulation and molecular docking, will be discussed. The simplifications and assumptions implicit in these approaches, as well as ways to improve their predictions will be covered.
Keynotes
Abstract
The concept that flavonoids, possessing well-known and characterized antioxidant capacity, can fight cancer is deeply rooted in the general population. On the opposite, a current of thought, argued by eminent scientists, attributes to free radical-destroying antioxidants the responsibility to negatively affect cancer incidence and therapy. The field is even more challenging considering that flavonoids possess both antioxidants and pro-oxidant activities and recent publications suggest that their beneficial anticancer effects can be easier explaining evoking the pro-oxidant capacity than the antioxidant one. In the present communication, we will analyze clinical and pre-clinical studies facing these sometimes paradoxical and contradictory concepts proposing that a clear distinction must be done between the use of flavonoids in cancer treatment versus cancer prevention, starting from adequate and specifically selected cellular and animal models. Among the multiple examples, the case of quercetin in chronic lymphocytic leukemia (CLL) will be considered. Quercetin, the most abundant flavonoid present in the diet, is able to modulate several hallmarks of cancer, including resistance to apoptosis. Our studies on this compound allowed us to decipher the biochemical pathway triggered by quercetin leading to demonstrate its capacity to synergistically sensitize several leukemia cell lines and B-cells isolated from CLL patients when associated with different classes of anticancer drugs. We also identified in the protein kinase CK2 the direct and primary target of quercetin, whose inhibition is correlated with the down-regulation of the PI3K/Akt signaling pathway and the massive apoptosis observed in CLL-derived cells. These data will be commented at the light of the very rapidly cellular uptake of quercetin and its capacity to lower intracellular concentrations of free radical species. Finally, considering the low toxicity of quercetin in normal peripheral blood cells, we will propose the design of clinical trials aimed to demonstrate its efficacy as a potential chemopreventive agent in the early phase of CLL.
Keynotes
The effects of strawberry bioactive compounds on lipid metabolism and adipogenesis
Abstract
Obesity is one of the major problems of the 21st century worldwide. It is characterized by an expansion of white adipose tissue (WAT) mass resulting from increased adipocytes number and/or size. Excessive accumulation of mature adipocytes is associated with high lipid levels and with a general impairment of catabolic pathways. In this work, we evaluated the effect of a strawberry extract on lipid metabolism and adipogenesis on HepG2 cells and 3T3-L1 adipocytes. The results demonstrated that in HepG2 strawberry extract stimulated the LKB1/AMPK pathway leading to the inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively; it also stimulated LDL receptor, sirtuin 1 (Sirt1) and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α). In addition, strawberry extract reduced 3T3-L1 pre-adipocytes differentiation, lipid accumulation and down-regulated the mRNA expression of the adipogenic transcription factors CCAAT/enhancer-binding protein (C/REB-α) and peroxisome proliferation-activated receptor (PPAR-γ). Consistently, it inhibited the expression of fatty acid binding protein (FABP4), ACC and sterol regulatory element-binding protein (SREBP1), by activating AMPK pathway. Strawberry extract also inhibited oxidative stress and inflammation biomarkers, increased antioxidant enzymes activities and mitochondrial functionality. Our results suggest the potential anti-obesity effect of the bioactive components of strawberry.
Keynotes
The role of antioxidants supplementation in clinical practice: focus on cardiovascular risk factors
Keynotes
Personalized Nutrition Plans based on Measurement of Specific Redox Biomarkers in Human Blood
by Dimitrios Koureta
Abstract
One of the most studied question in modern history is the particular way of bridging the gap between lifespan and healthspan? Even as average life expectancy has increased, there remains a sizeable gap between life span and health span — the years an individual lives without disease. The second question we must answer is the possibility that our lifespan and/or healthspan is “Programmed” in our genes? Or maybe there are other parameters that contribute to this model? Genome Analysis with “single nucleotide polymorphisms” (SNPs) of exceptionally long-lived people reveal 10-15% complex genetic signatures and very few genes consistently involved. The rest refers to the 3 pillars of metabolic health, the diet, the exercise, and the use of fasting in our everyday plan. Nutrient influence on healthy aging is being extensively studied in humans and in many animal models of aging. Moreover, the latest evidence is showing that regular physical activity can actually slow the aging process on a cellular level and potentially add years to your life. Additionally, intermittent fasting elicits evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation. All these measurements proposed by our research team provides a holistic approach for the evaluation of redox status parameters for several conditions. Therefore, the effect of personalized nutrition on human redox status is evaluated and human health is improved.
Keynotes
by Mihalis I. Panagiotidis
Abstract
Among the various types of dietary agents, isothiocyanates (ITCs) have raised the scientific interest with their unique properties, against disease development, including modulation of the epigenetic machinery. In the context of malignant melanoma, our research efforts have aimed to understand how ITCs induce cell death by interacting with the epigenetic machinery and thus leading to inhibition of tumor growth. For this purpose, we have utilized an experimental in vitro model of human malignant melanoma consisting of normal keratinocytes, primary and metastatic melanoma as well as non-melanoma epidermoid carcinoma cell lines. In this model, specific ITCs [e.g. sulforaphane (SFN), iberin (IBN) and allyl isothiocyanate (AITC)] were examined for their ability to influence histone acetylation and methylation marks, as a potential epigenetic therapeutic strategy against melanoma. Overall, we report that all ITCs inhibited melanoma cell proliferation and influenced acetylation and methylation status of specific lysine residues on H3 and H4 by modulating the expression of various histone acetyl transferases (HATs), histone deacetylases (HDACs) and histone methyl transferases (HMTs), in malignant melanoma cells. Our data highlight novel insights on SFN, IBN and AITC interaction with components of the histone regulatory machinery, to exert their anticancer action in malignant melanoma.