Marta Inglés

Oxidative Stress Is Related to Frailty, Not to Age or Sex, in a Geriatric Population: Lipid and Protein Oxidation as Biomarkers of Frailty

To ascertain whether indicators of oxidative damage to lipids (malondialdehyde (MDA)) and proteins (protein carbonylation) are biomarkers of frailty, after adjusting for age, sex, and other possible confounders.

Elevated protein carbonyl and HIF-1α levels in eyes with proliferative diabetic retinopathy.

Purpose:  To evaluate the role of protein carbonyls and hypoxia inducible factor‐1α (HIF‐1α) in diabetic eyes with proliferative diabetic retinopathy (PDR).

Pharmacological properties of physical exercise in the elderly.

Scientific evidence links physical activity to several benefits. Recently, we proposed the idea that exercise can be regarded as a drug. As with many drugs, dosage is of great importance. However, to issue a public recommendation of physical activity in aging is not an easy task. Exercise in the elderly needs to be carefully tailored and individualized with the specific objectives of the person or group in mind. The beneficial effects of exercise in two of the main age-related diseases, sarcopenia and Alzheimers Disease, are dealt with at the beginning of this report. Subsequently, dosage of exercise and the molecular signaling pathways involved in its adaptations are discussed. Exercise and aging are associated with oxidative stress so the paradox arises, and is discussed, as to whether exercise would be advisable for the aged population from an oxidative stress point of view. Two of the main redox-sensitive signaling pathways altered in old skeletal muscle during exercise, NF-κB and PGC-1α, are also reviewed. The last section of the manuscript is devoted to the age-associated diseases in which exercise is contraindicated. Finally, we address the option of applying exercise mimetics as an alternative for disabled old people. The overall denouement is that exercise is so beneficial that it should be deemed a drug both for young and old populations. If old adults adopted a more active lifestyle, there would be a significant delay in frailty and dependency with clear benefits to individual well-being and to the publics health.

Resveratrol: distribución, propiedades y perspectivas

Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts, mulberries, blueberries and, above all, in grapes and red wine. Its synthesis is regulated by the presence of stressful factors, such as fungal contamination and ultra-violet radiation. In plants, it plays a role as a phytoalexin, showing a capacity to inhibit the development of certain infections. Plant extracts which contain resveratrol have been employed by traditional medicine for more than 2000 years. Resveratrol was first isolated, and its properties were initially studied with scientific methods, thirty years ago. Its in vitro properties have been extensively studied and demonstrated. It is worth highlighting its activity as an anti-cancer agent, platelet anti-aggregation agent, anti-inflammatory, antiallergenic, etc. The activity of its in vivo properties are not so clear. There are many studies that report benefits on the cardiovascular system, illnesses such as diabetes, and in longevity. However, other authors did not find any agreement between in vitro and in vivo studies. This discrepancy is due to the bioavailability of resveratrol. After an oral dose, it has been demonstrated that the absorption is very high, but the metabolic pathways leave just a little free resveratrol in blood, therefore the bioavailability in the target tissues is very low and the concentrations used in in vitro studies are not found in these tissues. Thus, resveratrol is a very active molecule for maintaining health, but due to the low bioavailability not all the in vitro effects can be translated to in vivo. This opens a new potential approach, seeking derivatives of resveratrol that can be measured in the desired tissues.

PTEN Mediates the Antioxidant Effect of Resveratrol at Nutritionally Relevant Concentrations

Introduction. Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant. Aims. In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect. Methods. We used mammary gland tumor cells (MCF-7), which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy). Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results. Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM). This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels. Conclusion. Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway.

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl - xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl- xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl-xL display a reduction in senescent-related markers. Finally, to demonstrate the role of BcL-xL in longevity at the organism level, C. elegans bearing a gain of function mutation in the BcL-xL ortholog ced-9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that BcL- xL plays an important role in exceptional aging.

Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review

Objectives: The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Methods: Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004–2014). The following terms were used: “patellofemoral pain syndrome,” “physical therapy,” “manual therapy,” and “manipulation.” RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Results: Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. Conclusions: The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

Potential role of physiotherapists in polymedication of the elderly.

magnetic resonance imaging, dual energy X-ray absorptiometry (DXA) and BIA are available for the measurement of skeletal muscle mass. To date, especially for research purposes, DXA has been the most widely preferred technique in SMM measurement in the elderly. The formula produced by Janssen et al., which relies on non-segmental BIA-derived resistance (muscle mass = 0.401 ¥ [height / BIA resistance] + (3.82 ¥ sex [0.071 ¥ age] + 5.102) is another compelling tool to measure SMM. However, there is limited data on the validity of direct measurement of skeletal muscle mass by segmental BIA among the elderly. In an early study by Mally et al., muscle mass was underestimated in men’s limbs and overestimated in women’s left arm by segmental BIA measurement. Furthermore, a study in a Japanese sample concluded that segmental BIA underpredicted right arm and right leg muscle mass as compared with DXA as the reference. Accurate measurement of SMM is of particular importance when defining sarcopenia in the elderly. Collectively, because the results of direct SMM measurement by segmental BIA were used in the main analyses in the present study by Tanimoto et al., some of their participants might have been misclassified because of the risk of estimation errors regarding the methodological approach. Therefore, before reaching definite conclusions, the influences of such a potential misclassification on the results and what data would be obtained when validated methods were used in such a population should be reassured. This would also help improve the methodological design of future population studies on sarcopenia.

Identificación de polimorfismos de un solo nucleótido relacionados con la fragilidad

INTRODUCTION The search for biomarkers that can lead to the early diagnosis and thus, early treatment of frailty, has become one of the main challenges facing the geriatric scientific community. The aim of the present study was to identify single nucleotide polymorphisms (SNPs) related to frailty. MATERIAL AND METHODS The study was conducted on 152 subjects from the Toledo Study for Healthy Aging (65 to 95 years of age), and classified as frail (n=78), and non-frail (n=74), according to Frieds criteria. After blood collection, DNA was isolated and amplified for the analysis of SNPs using AxiomTM Genotyping technology (Affymetrix). Statistical analyses were performed using the Plink program and library SNPassoc. RESULTS The results of the study showed 15 SNPs with a P<.001. Those SNPs involved in processes related to frailty, such as energy metabolism, regulation of biological processes, cell motility and integrity, and cognition are highlighted. CONCLUSIONS These results suggest that the genetic variations identified in frail individuals that are involved in biological processes related to frailty may be considered as biomarkers for the early detection of frailty.

Identificación de polimorfismos de nucleótido simple en centenarios

INTRODUCTION Longevity is determined by genetic and external factors, such as nutritional, environmental, social, etc. Nevertheless, when living conditions are optimal, longevity is determined by genetic variations between individuals. In a same population, with relative genotypic homogeneity, subtle changes in the DNA sequence affecting a single nucleotide can be observed. These changes, called single nucleotide polymorphisms (SNP) are present in 1-5% of the population. MATERIAL AND METHODS A total of 92 subjects were recruited, including 28 centenarians and 64 controls, in order to find SNP that maybe implicated in the extreme longevity, as in the centenarians. Blood samples were collected to isolate and amplify the DNA in order to perform the analysis of SPN by Axiom™ Genotyping of Affymetrix technology. Statistical analyses were performed using the Plink program and libraries SNPassoc and skatMeta. RESULTS Our results show 12 mutations with a p<.001, where 5 of these (DACH1, LOC91948, BTB16, NFIL3 y HDAC4) have regulatory functions of the expressions of others genes. CONCLUSIONS Therefore, these results suggest that the genetic variation between centenarians and controls occurs in five genes that are involved in the regulation of gene expression to adapt to environmental changes better than controls.