[Precision dietary guidelines and ingredients for chronic diseases in pre-senior and senior populations]. / Estrategias de guía e ingredientes dietéticos de precisión para enfermedades crónicas en población pre-sénior y sénior.

The aging of the population underlines an important challenge for the health system not only from sanitary and economic reasons but also by quality perspectives concerning preventive care, where precision nutrition (PN) and the prescription or advice on healthy habits becomes relevant. PN focuses on provide nutrition adapted to each individual, understanding that the prevention or treatment of chronic disorders (obesity, diabetes, cardiovascular disease, etc.) must be addressed in a comprehensive way, considering not only relevant personal and clinical information, but also healthy aging and phenotypical and genotypical features. This guide was prepared due to the need to develop precision nutritional models that allow individualized nutritional treatment for each subject and physiopathological particularities with emphasis on the elderly. Therefore, the requirements of the Spanish pre-senior and senior populations, dietary recommendations and precision foods are reviewed in this document: have at least three daily meals, reduce total calories, choose a varied and balanced diet with fresh foods and high nutritional density, add vegetables, legumes and fish, consume dairy products and fiber, prefer white meat instead of red, avoid fried foods, sausages and processed foods, moderate the consumption of salt, coffee and alcohol, and get hydrated.

Estrategias de guía e ingredientes dietéticos de precisión para enfermedades crónicas en población pre-sénior y sénior / Precision dietary guidelines and ingredients for chronic diseases in pre-senior and senior populations

El envejecimiento de la población supone un importante reto, económico y cualitativo, para el sistema de salud orientándolo hacia una atención de tipo preventivo, en la que la nutrición de precisión (NP) y la prescripción de hábitos saludables adquieren relevancia capital. El fin de la NP es procurar una nutrición adaptada a cada individuo, entendiendo que la prevención o el tratamiento de trastornos crónicos (obesidad, diabetes, enfermedad cardiovascular, etc.) deben abordarse de un modo integral, considerando información personal y clínica relevante, edad y características feno- y genotípicas. La elaboración de la presente guía surge de la necesidad de desarrollar modelos nutricionales de precisión que permitan la individualización del tratamiento nutricional, con énfasis en el adulto mayor. Las necesidades nutricionales, las recomendaciones dietéticas y los ingredientes para una NP en las personas pre-sénior y sénior quedan resumidas en realizar al menos 3 comidas diarias, reducir las calorías totales, optar por una alimentación variada y equilibrada con alimentos frescos y de alta densidad nutricional, incorporar verduras, legumbres y pescado, consumir productos lácteos y fibra, preferir carnes blancas en lugar de rojas, evitar frituras, embutidos y alimentos procesados, moderar el consumo de sal, café y alcohol, e hidratarse adecuadamente

The aging of the population underlines an important challenge for the health system not only from sanitary and economic reasons but also by quality perspectives concerning preventive care, where precision nutrition (PN) and the prescription or advice on healthy habits becomes relevant. PN focuses on provide nutrition adapted to each individual, understanding that the prevention or treatment of chronic disorders (obesity, diabetes, cardiovascular disease, etc.) must be addressed in a comprehensive way, considering not only relevant personal and clinical information, but also healthy aging and phenotypical and genotypical features. This guide was prepared due to the need to develop precision nutritional models that allow individualized nutritional treatment for each subject and physiopathological particularities with emphasis on the elderly. Therefore, the requirements of the Spanish pre-senior and senior populations, dietary recommendations and precision foods are reviewed in this document: have at least three daily meals, reduce total calories, choose a varied and balanced diet with fresh foods and high nutritional density, add vegetables, legumes and fish, consume dairy products and fiber, prefer white meat instead of red, avoid fried foods, sausages and processed foods, moderate the consumption of salt, coffee and alcohol, and get hydrated

The gut microbiota urolithin metabotypes revisited: the human metabolism of ellagic acid is mainly determined by aging.

Understanding individuals' response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n = 839) that aging is the main factor that determines the gut microbiota involved in the ellagic acid-ellagitannin metabolism (urolithin metabotypes), with potential consequences for human health.

Antiproliferative effect of alkylglycerols as vehicles of butyric acid on colon cancer cells.

The anticarcinogenic activity of synthetic 1-O-octadecyl-2,3-dibutyroilglycerol (D-SCAKG) in tumor-cell line of colonocytes (SW620) was performed. The effect of the previously digested D-SCAKG under in vitro intestinal conditions was compared to the bioactivity of non-digested D-SCAKG. Antiproliferative activity of each individual product from digestion (1-O-octadecyl-2-butyroilglycerol; 1-O-octadecyl glycerol; butyric acid) was also performed. The impact of solubilization of lipid products within micellar structures was also tested. The 1-O-octadecyl glycerol was the most active compound, followed by 1-O-octadecyl-2-butyroilglycerol, D-SCAKG and butyric acid. The 1-O-octadecyl glycerol and butyric acid were the only molecules that showed antiproliferative effect in absence of micelles. Digested D-SCAKG was 4-fold more effective than non-digested D-SCAKG. A synergism between 1-O-octadecyl-2-butyroilglycerol and 1-O-octadecyl glycerol was evidenced. As summary, the synthetic D-SCAKG seems to be an interesting antitumoral lipid against colonocytes, especially after previous intestinal digestion, and mainly due to the synergism of the major products, namely 1-O-octadecyl-2-butyroilglycerol and 1-O-octadecyl glycerol. At the same time, 1-O-octadecyl-2-butyroilglycerol would constitute a stable esterified form of butyric acid for its vehiculization.

Acid ceramidase as a chemotherapeutic target to overcome resistance to the antitumoral effect of choline kinase α inhibition.

We have analyzed the response of primary cultures derived from tumor specimens of non small cell lung cancer (NSCLC) patients to choline kinase α (ChoKα) inhibitors. ChoKα inhibitors have been demonstrated to increase ceramides levels specifically in tumor cells, and this increase has been suggested as the mechanism that explain its proapoptotic effect in cancer cells. Here, we have investigated the molecular mechanism associated to the intrinsic resistance, and found that other enzyme involved in lipid metabolism, acid ceramidase (ASAH1), is specifically upregulated in resistant tumors. NSCLC cells with acquired resistance to ChoKα inhibitors also display increased levels of ASAH1. Accordingly, ASAH1 inhibition synergistically sensitizes lung cancer cells to the antiproliferative effect of ChoKα inhibitors. Thus, the determination of the levels of ASAH1 predicts sensitivity to targeted therapy based on ChoKα specific inhibition and represents a model for combinatorial treatments of ChoKα inhibitors and ASAH1 inhibitors. Considering that ChoKα inhibitors have been recently approved to enter Phase I clinical trials by the Food and Drug Administration (FDA), these findings are anticipating critical information to improve the clinical outcome of this family of novel anticancer drugs under development.

A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas.

Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKalpha show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoKalpha plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoKalpha is constitutively altered in human bladder tumor cells. Furthermore, in vivo murine models, including an orthotopic model to mimic as much as possible the physiological conditions, revealed that increased levels of ChoKalpha potentiate both tumor formation (P< or =0.0001) and aggressiveness of the disease on different end points (P=0.011). Accordingly, increased levels of ChoKalpha significantly reduce survival of mice with bladder cancer (P=0.05). Finally, treatment with a ChoKalpha-specific inhibitor resulted in a significant inhibition of tumor growth (P=0.02) and in a relevant increase in survival (P=0.03).

Inhibition of ChoK is an efficient antitumor strategy for Harvey-, Kirsten-, and N-ras-transformed cells.

An increasing amount of evidence suggests that elevated PCho levels are related to the transforming properties of the H-Ras oncoprotein. Based on these observations, we have designed an antitumor strategy using choline kinase, the enzyme responsible of PCho production, as a novel target for drug discovery. However, little relationship between this lipid-related pathway and the other two Ras members, N- and K-ras, has been established. Since N- and K-ras are the most frequently mutated ras genes in human tumors, we have analyzed the PC-PLD/ChoK pathway and the sensitivity to ChoK inhibition of all three ras-transformed cells. Here we demonstrate that transformation by the three Ras oncoproteins results in increased levels of PCho to a similar extent, resulting from a similar constitutive increase of ChoK activity. As well, sensitivity to choline kinase inhibitors as antiproliferative drugs is similar in cell lines transformed by each of the three ras oncogenes, being in all cases higher than parental, nontransformed cells. In addition, H, K and N-ras-induced alterations in PC metabolism is discussed. These results indicate that ChoK can be used as a general target for anticancer drug design against Ras-dependent tumorigenesis.

Targeting new anticancer drugs within signalling pathways regulated by the Ras GTPase superfamily (Review).

A dynamic equilibrium or is responsible for the proper function of a living organism. Physiological events regulating proliferation, apoptosis, differentiation, and cell arrest, modulates the correct homeostasis and functionality of all tissues. Cancer is a consequence of a disorder in these sequential events, which results in the alteration of the ratio between cell death, cell differentiation and cell proliferation that ultimately leads to an increase in the number of dysregulated cells. Most of the processes which control the are regulated by signalling pathways, whose components are currently being explored as potential targets for the design of antitumoral drugs. Many in vivo studies have shown that Ras and Rho proteins are key modulators of mitogenic signalling, and are involved in the carcinogenesis of several human tumors. The development of recent drugs that elicit antitumoral activity by blocking some of the Ras and/or Rho effects, is discussed in this review.