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Despite the great progress and advancements in scientific knowledge, technology, and medicine, viral infections continue to put human health in trouble. Both acquired immunodeficiency syndrome (AIDS) and coronavirus disease 2019 (COVID-19), caused by human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2, two RNA viruses responsible for global pandemics, respectively, have poor outcomes associated with increased oxidative stress, systemic inflammation, and immunopathology. Here, we have collected the current knowledge linking both viral infections, focusing on the role of oxidative stress and the redox balance. Furthermore, we provide information on some redox-active compounds, such as vitamins, thiol-based agents, and polyphenols, and their possible beneficial effects on both diseases. Thus, in this review, we aim to highlight the importance and impact of nutritional strategies to strengthen our immune system, especially to increase the effectiveness of pharmacological treatments, or when there are no effective treatments.

Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer’s disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer’s disease and in the neuronal migration process using the APP/PS1 Alzheimer’s mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer’s disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer’s based on senolytic compounds or pro-neurogenic factors.

Familial longevity confers advantages in terms of health, functionality, and longevity. We sought to assess potential differences in frailty and sarcopenia in older adults according to a parental history of extraordinary longevity. A total of 176 community-dwelling subjects aged 65–80 years were recruited in this observational case–control study, pair-matched 1:1 for gender, age, and place of birth and residence: 88 centenarians’ offspring (case group) and 88 non-centenarians’ offspring (control group). The main variables were frailty and sarcopenia based on Fried’s phenotype and the European Working Group on Sarcopenia in Older People (EWGSOP) definitions, respectively. Sociodemographics, comorbidities, clinical and functional variables, the presence of geriatric syndromes, and laboratory parameters were also collected. Related sample tests were applied, and conditional logistic regression was performed. Cases had a higher percentage of robust patients (31.8% vs. 15.9%), lower percentages of frailty (9.1% vs. 21.6%) and pre-frailty (59.1% vs. 62.5%) (p = 0.001), and lower levels of IL-6 (p = 0.044) than controls. The robust adjusted OR for cases was 3.00 (95% CI = 1.06–8.47, p = 0.038). No significant differences in muscle mass were found. Familial longevity was also associated with less obesity, insomnia, pain, and polypharmacy and a higher education level and total and low-density lipoprotein cholesterol. The results suggest an inherited genetic component in the frailty phenotype, while the sarcopenia association with familial longevity remains challenging.

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of “omic” techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30–100 years old; 2: n = 68, 70% females, 19–107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial β-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases. This research was funded by the Spanish Ministry of Science,Innovation, and Universities (grant RTI2018-099200-B- I00, and PID2022-143140OB-I00, co-funded by the European Regional Development Fund. “A way to build Europe”), and the Generalitat of Catalonia (Agency for Management of University and Research Grants [2021SGR00990] and Department of Health [SLT002/16/00250])to R.P. The work is also supported by “la Caixa” Foundation (Grant Agreement LCF/PR/HR21/52410002) to M.J. IRBLleida is a CERCAProgramme/Generalitat of Catalonia. This work was also partiallysupported by Instituto de Salud Carlos III (Madrid, Spain) through the research grants PI15/01934, PI18/01022, PI20/01090, and PI21/01361 (co-funded by the European Regional Development Fund. “A way to make Europe”), and the Catalan Government (AGAUR,#SGR2017-0734, ICREA Academia Award 2021) to J.M.F-R.

BackgroundDelaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics.Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model.MethodsIn this double-blind, placebo-controlled, bicentric clinical trial we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 early symptomatic Alzheimer’s patients. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T) Clock-drawing test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.ResultsWe report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p=0.031; dichotomized delayed centil REY copy p=0.002 and a tendency to improve in all the rest of them.The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake which showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878) while placebo-treated did increase it (p=0.036) We did not observe significant changes in other brain areas studiedConclusionsThis study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with mild cognitive impairment. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.Trial registrationNCT01982578

The increase of vascular arginase activity during aging causes endothelial dysfunction. This enzyme competes with the endothelial nitric oxide synthase (eNOS) for L-arginine substrate. Our hypothesis is that glucose 6-P dehydrogenase (G6PD) overexpression could improve the endothelial function modulating the arginase pathway in aorta from mice. For this study, three groups of male mice were used: young wild type (WT) (6–9 months), old WT (21–22 months) and old G6PD-Tg (21–22 months) mice. Vascular reactivity results showed a reduced acetylcholine-dependent relaxation in the old WT but not old G6PD-Tg group. Endothelial dysfunction was reverted by nor-NOHA, an arginase inhibitor. Mice overexpressing G6PD underexpressed arginase II and also displayed a lower activity of this enzyme. Moreover, histological analyses demonstrated that age causes a thickness of aortic walls, but this did not occur in G6PD-Tg mice. We conclude that the overexpressing G6PD mouse is a model to improve vascular health via the arginase pathway.

Frailty is prevalent in older adults and is related to a worsening functionality, quality of life, and health outcomes. Though there is an increasing interest in this field, the relationship between frailty and worsening COPD outcomes remains unknown. A narrative review of the literature with studies published between 2018 and 2022 was carried out to address three questions: the prevalence of frailty and other geriatric syndromes in COPD patients, the link between frailty and worsening health outcomes in COPD patients, and the non-pharmacological interventions performed in order to reverse frailty in these patients. A total of 25 articles were selected. Frailty prevalence ranged from 6% and 85.9%, depending on the COPD severity and the frailty measurement tool used. Frailty in COPD patients was related to a high prevalence of geriatric syndromes and to a high incidence of adverse events such as exacerbations, admissions, readmissions, and mortality. One study showed improvements in functionality after physical intervention. In conclusion, the prevalence of frailty is associated with a high incidence of geriatric syndromes and adverse events in COPD patients. The use of frailty screenings and a comprehensive geriatric assessment of COPD patients is advisable in order to detect associated problems and to establish individualized approaches for better outcomes.

In order to investigate the possible beneficial effects of GH administration on the aging process, 24-month-old rats of both sexes and 10-month-old SAMP8 mice were used. Male rats showed increased fat content and decreased lean body mass together with enhanced vasoconstriction and reduced vasodilation of their aortic rings compared to young adult animals. Chronic GH treatment for 10 weeks increased lean body mass and reduced fat weight together with inducing an enhancement of the vasodilatory response by increasing eNOS and a reduction of the constrictory responses. Old SAMP8 male mice also showed insulin resistance together with a decrease in insulin production by the endocrine pancreas and a reduced expression of differentiation parameters. GH treatment decreased plasma levels and increased pancreatic production of insulin and restored differentiation parameters in these animals. Ovariectomy plus low calcium diet in rabbits induced osteoporosis Titanium implants inserted into these rabbit tibiae showed after one month lesser bone to implant (BIC) surface and bone mineral density (BMD). Local application of GH in the surgical opening was able to increase BIC in the osteoporotic group. The hippocampus of old rats showed a reduction in the number of neurons and also in neurogenesis compared to young ones, together with an increase of caspases and a reduction of Bcl-2. GH treatment was able to enhance significantly only the total number of neurons. In conclusion, GH treatment was able to show beneficial effects in old animals on all the different organs and metabolic functions studied.

Brain ageing is produced by various morphological, biochemical, metabolic and circulatory changes, which are reflected in functional changes, whose impact depends on the presence or absence of cognitive impairment. Because of brain plasticity, together with redundancy of the distinct cerebral circuits, age- related deterioration of the brain at various levels does not always translate into loss of brain function. However, when the damage exceeds certain thresholds, there is age-related cognitive impairment, which increases the risk of developing various neurodegenerative diseases such as Alzheimer disease. Genetics, together with lifestyle, diet, and environmental factors, etc, can trigger the development of these diseases, which provoke cognitive impairment. This article discusses the most important age-related changes in the brain, as well as the pathophysiological foundations of cognitive impairment.

Resumen Introduccion La longevidad humana es un fenomeno complejo en el que influyen factores geneticos y ambientales. El estres oxidativo (EO) puede jugar un papel importante en este proceso. El envejecimiento exitoso podria relacionarse con la habilidad del organismo para hacer frente al EO. Nuestro objetivo es comparar los niveles en plasma de malondialdehido (MDA) y proteinas oxidadas (PO) entre sujetos mayores de 97 anos y con edad entre 70 y 80 anos, para comprender mejor los efectos del estres oxidativo en la longevidad humana. Material y metodos Estudio de casos y controles de base poblacional. Se consideraron casos todas aquellas personas nacidas y residentes en la comarca de la Ribera (Valencia), con edad superior a 97 anos y que aceptaron participar en el mismo. Los controles son sujetos de la misma base poblacional, elegidos al azar, y con edad entre 70 y 80 anos. Se realiza un analisis descriptivo de variables sociodemograficas, clinicas y funcionales; se calcula la razon de odds (OR) de ser centenario en funcion del cuartil de los niveles de PO y MDA; y la significacion estadistica de la tendencia mediante el test Mantel-Haenszel. Resultados Fueron incluidos 28 casos y 31 controles. La situacion funcional, asi como el porcentaje de individuos robustos, fue menor en el grupo de casos que en los controles. Los niveles de MDA fueron menores en los casos (1,44 ± 0,45 vs. 1,84 ± 0,59, p = 0,005), al igual que los niveles de PO (64,29 ± 15,73 vs. 76,52 ± 13,44, p = 0,002). Al comparar a los sujetos con niveles de MDA y PO en el cuartil inferior respecto al superior, la OR de ser centenario es de 3,8 para el MDA y de 5,7 para las PO, con una p = 0,029 y p = 0,044, respectivamente, en la significacion de la tendencia. Conclusiones En los sujetos de nuestro estudio los niveles plasmaticos de MDA y PO son menores en centenarios que en ancianos mas jovenes, y se observa que a menor grado de EO mayor es la probabilidad de ser centenario.

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.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 Fried's criteria. After blood collection, DNA was isolated and amplified for the analysis of SNPs using AxiomThe 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.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.

Brain ageing is produced by various morphological, biochemical, metabolic and circulatory changes, which are reflected in functional changes, whose impact depends on the presence or absence of cognitive impairment. Because of brain plasticity, together with redundancy of the distinct cerebral circuits, age- related deterioration of the brain at various levels does not always translate into loss of brain function. However, when the damage exceeds certain thresholds, there is age-related cognitive impairment, which increases the risk of developing various neurodegenerative diseases such as Alzheimer disease. Genetics, together with lifestyle, diet, and environmental factors, etc, can trigger the development of these diseases, which provoke cognitive impairment. This article discusses the most important age-related changes in the brain, as well as the pathophysiological foundations of cognitive impairment.

Resumen Fundamento y objetivo Nuestro objetivo fue caracterizar el perfil de factores de riesgo vascular que presentan diferentes enfermedades vasculares oclusivas de la retina, como son la trombosis venosa, la embolia arterial y la neuropatia optica isquemica anterior (NOIA). Para eso estudiamos a los pacientes que diagnostico el servicio de oftalmologia sobre la base de criterios clinicos, funduscopicos y angiograficos. Pacientes y metodo Estudio transversal de 284 sujetos con enfermedades vasculares de la retina entre 25–93 anos de edad a los que se selecciono consecutivamente en la consulta de oftalmologia y que se remitieron a la consulta de medicina interna. Resultados De 284 pacientes, el 52 % eran varones y el 48 % eran mujeres, con una edad media (DE) de 62 (12) anos (intervalo: 25–93 anos). La trombosis venosa retiniana era la enfermedad mas frecuente, con un 66 % (intervalo de confianza [IC] del 95%: 60,4–71,5), seguida de la NOIA, con un 21% (IC del 95%: 16,1–25,8) y la embolia arterial, con un 11% (IC del 95 %: 7,29–14,7). En conjunto, presentaban alta prevalencia de antecedentes de factores de riesgo vascular, sobre todo hipertension arterial, en un 50 % (IC del 95%: 44,0–55,9), y sindrome metabolico en un 39% (IC del 95%: 33,2–44,7). Individualmente, la trombosis venosa retiniana se asocio a hipertension arterial con hipertrofia ventricular izquierda en el 54% (p Conclusiones Las enfermedades vasculares oclusivas de la retina globalmente se asocian a factores de riesgo vascular pero con caracteristicas especificas en cada enfermedad.

Increased serum homocysteine levels are related to vascular disease and increased mortality. The decrease of homocysteine is also associated with a worse prognosis in patients on hemodialysis; however, this relationship has not been well studied in other patients. Our goal is to study the prognosis of increased and decreased serum homocysteine levels in elderly patients admitted to a general internal medicine unit.We included 239 patients (121 women and 118 men; mean age, 78 years) in which we determined serum homocysteine levels and study its relationship with vascular risk factors, vascular disease: ischemic heart disease, ischemic stroke and peripheral arterial disease, nutritional status, creatinine, albumin, folate and B12 vitamin.Mortality during hospitalization of patients with homocysteine levels below 9 μmol/l was 33%, 9% for those with levels between 9 and 20 μmol/l and 17% for those with levels above 20 μmol/l. Low homocysteine values were related to increased comorbidity, higher degree of weight loss and decreased serum albumin levels. In a survival analysis using Kaplan-Meier curves, increased homocysteine was associated with increased mortality especially in patients with vascular disease.In elderly patients with multiple comorbidities, both decreased and increased serum homocysteine levels are associated with increased mortality.Antecedentes y objetivos: el aumento de la homocisteína se relaciona con la enfermedad vascular y un incremento de la mortalidad. La disminución de la homocisteína se asocia también con un peor pronóstico en enfermos en hemodiálisis; sin embargo, esta relación no ha sido bien estudiada en otro tipo de pacientes. El objetivo del estudio fue analizar el valor pronóstico de los niveles de homocisteína en enfermos ancianos pluripatológicos ingresados en un servicio general de medicina interna Pacientes y métodos: estudiamos a 239 pacientes (121 mujeres y 118 varones; edad media: 78 años) en los que determinamos la homocisteína sérica y la relacionamos con los factores de riesgo vascular, enfermedad vascular: cardiopatía isquémica, ACV isquémico y arteriopatía periférica, estado de nutrición, creatinina, albúmina, ácido fólico y vitamina B12. Resultados: la mortalidad durante el ingreso de los enfermos con homocisteína menor de 9 mol/l fue del 33%, del 9% cuando estaba entre 9 y 20 mol/l y del 17% si era superior a 20 mol/l. La disminución de la homocisteína se relacionó con mayor comorbilidad, pérdida de peso y disminución de la albúmina. A largo plazo, el aumento de la homocisteína se relacionó con mayor mortalidad, especialmente en los pacientes con enfermedad vascular. Conclusión: en los pacientes ancianos pluripatológicos tanto la disminución como el aumento de la homocisteína se asocian con una mayor mortalidad.

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.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.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.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.

Resumen Introduccion las hembras viven mas que los machos. Hemos demostrado que los estrogenos son capaces de aumentar la expresion de genes asociados a la longevidad. Sin embargo, nos hemos centrado en el estudio de genes cuya relacion con la longevidad esta muy bien establecida. Por esto, nos planteamos el estudio de 9.000 genes mediante el metodo del Genechip. Estudiamos la expresion de estos genes en machos y los comparamos con la expresion en las hembras. Material y metodo la expresion de los genes se estudio mediante la tecnologia Affymetrix. En esencia, aislamos ARN total y lo pasamos a ADNc de doble cadena por retrotranscripcion. Obtenemos ARN marcado con biotina a partir del ADNc y lo purificamos. La muestra se introduce en un bioarray U34A y se procesa en la estacion de fluidos Affymetrix. Los resultados se escanean y analizan con el programa Microarray Suite 3.0. Resultados encontramos 33 genes cuya expresion es significativamente mayor en el macho que en la hembra y 53 genes que se sobrexpresan en la hembra comparada con el macho. Estudiamos en particular los genes cuya expresion cambiaba mas de 2 veces, y vemos que todos estos genes estan relacionados con el envejecimiento. Por tanto, encontramos genes que se sobrexpresan en la hembra respecto del macho y previamente no habian sido identificados como relacionados con el sexo. Conclusiones el analisis multigenico es una herramienta util para identificar genes sobrexpresados en las hembras en relacion con los machos y que sean relevantes en el proceso de envejecimiento.

Resumen Introduccion la enfermedad de Alzheimer (EA) es uno de los problemas sociosanitarios mas importantes actualmente. Se considera la toxicidad del peptido beta-amiloide la clave de su patogenia. Cada vez es mas importante conseguir marcadores perifericos de la enfermedad para avanzar en su conocimiento y de sus posibles dianas terapeuticas. Con este estudio pretendemos valorar la idoneidad de los linfocitos como modelo en el que estudiar la toxicidad del beta-amiloide. Material y metodos se recluto a 6 voluntarios sanos, 3 varones y 3 mujeres, con edades comprendidas entre los 25 y 35 anos, sin antecedentes familiares de EA. Se les realizo una extraccion sanguinea de donde se aislaron los linfocitos que posteriormente se incubaron con beta-amiloide 1-42 durante 6 h. Se utilizo la microscopia confocal y la citometria de flujo para estudiar, como marcadores de toxicidad celular, la apoptosis, el potencial de membrana mitocondrial y el numero de mitocondrias. Resultados encontramos un aumento de muerte celular en sus distintos estadios (apoptosis temprana y tardia) asi como una disminucion de mitocondrias en los linfocitos incubados con el peptido beta-amiloide. Observamos un mayor dano celular en los linfocitos de los varones que en las mujeres, probablemente por el efecto protector de los estrogenos. Conclusiones los linfocitos son un buen modelo para estudiar la toxicidad celular del peptido beta-amiloide.

Redox-sensitive cell signalling Thiol groups and the regulation of gene expression Redox-sensitive signal transduction pathways Protein kinases Protein phosphatases Lipids and phospholipases Antioxidant (electrophile) response element Intracellular calcium signalling Transcription factors NF-?B AP-1 p53 Cellular responses to oxidative stress Cellular responses to change in redox state Proliferation Cell death Immune cell function Reactive oxygen and nitrogen species – good or bad? Reactive oxygen species and cell death Reactive oxygen species and inflammation Are specific reactive oxygen species and antioxidants involved in modulating cellular responses? Specific effects of dietary antioxidants in cell regulation Carotenoids Vitamin E Flavonoids Inducers of phase II enzymes Disease states affected Oxidants, antioxidants and mitochondria Introduction Mitochondrial generation of reactive oxygen and nitrogen species Mitochondria and apoptosis Mitochondria and antioxidant defences Key role of mitochondrial GSH in the defence against oxidative damage Mitochondrial oxidative damage Direct oxidative damage to the mitochondrial electron transport chain Nitric oxide and damage to mitochondria Effects of nutrients on mitochondria Caloric restriction and antioxidants Lipids Antioxidants Techniques and approaches Mitochondrial techniques cDNA microarray approaches Proteomics approaches Transgenic mice as tools in antioxidant research Gene knockout and over expression Transgenic reporter mice Conclusions Future research needs

This paper assesses critically the science base that underpins the argument that oxidative damage is a significant causative factor in the development of human diseases and that antioxidants are capable of preventing or ameliorating these disease processes. The assessment has been carried out under a number of headings, and some recommendations for future research are made based on the present day knowledge base. The knowledge database (1) Consideration of the basic science that underlies understanding of the role of free radicals in causing cellular pathologies, and the role of antioxidants in preventing this, shows that an imbalance of reactive oxygen species and antioxidant defence systems may lead to chemical modifications of biologically relevant macromolecules. This imbalance provides a logical pathobiochemical mechanism for the initiation and development of several disease states. Experimental data obtained in vivo provide evidence that antioxidants function in systems that scavenge reactive oxygen species and that these are relevant to what occurs in vivo. The relevance in vivo of these observations depends inter alia on knowledge of the uptake and distribution of the antioxidant within the human body, and on what tissue levels of the antioxidant may be expected in relation to dietary levels. (2) There is some way to go until validated precise methods are available for measuring biomarkers of oxidative damage in human subjects in vivo under minimally invasive conditions. With respect to oxidative damage in DNa, HPLC and GC-mass spectrophotometry methods have both merits and limitations. Lipid oxidation products in plasma are best measured as isoprostanes or as lipid hydroperoxides using specific HPLC techniques. Development of isoprostane measurement will advance specificity and precision. The measurement of oxidative damage to proteins has some potential but such methods have not been effectively exploited. (3) Epidemiological studies support the hypothesis that the major antioxidant nutrients vitamin E and vitamin C, and beta-carotene (which may or may not be acting as an antioxidant in vivo), may play a beneficial role in prevention of several chronic disorders. More research is needed on the impact of other non-nutrient compounds, such as other carotenoids and flavonoids, on human health. In general, human intervention studies using hard end-points are the gold standard. Trials are restricted mainly to the major antioxidants and do not allow firm conclusions because of inconsistent findings, an insufficient number of studies and the use of varying doses. There is evidence that large doses of beta-carotene may be deleterious to the health of certain subgroups of the population such as heavy habitual smokers. (4) With respect to the safety of administration of supplementary vitamins, vitamin C is safe at levels of supplementation up to 600 mg/d, and higher levels, up to 2000 mg/d, are without risk. Vitamin E has a very low human toxicity and an intake of 1000 mg/d is without risk; 3200 mg/d has been shown to be without any consistent risk. Large intakes of beta-carotene must be viewed with caution because they have been shown to confer detriment to a population at high risk of lung cancer when administered after many years of high risk (smoking) behaviour. Until further work clarifies the situation in heavy smokers with respect to taking supplements, larger doses should be avoided by such individuals. There is little reliable information about the human toxicology of flavonoids and related non-nutrient antioxidant constituents of the diet. (5) The food industry has long experience in the control of oxidative damage in foods and this experience can be used to advantage for the protection of food antioxidants which are beneficial. Some of these, such as vitamins C and E and beta-carotene, are well known, and strategies for their protection in foods are already exploited by food technologies. (ABSTRACT TRUNCATED)

Human longevity is a complex issue influenced by genetic and environmental factors. Oxidative stress (OE) could play an important role in this process. Succesful aging could be related with the organism ability facing OE. In the present study we compared malondialdehyde (MDA) and oxidized proteins (OP) plasma levels, in elderly people older than 97 years and 70-80 years old, to better understand the effects of OE on human longevity.Population-based case control study. We considered as cases patients who were born and live on la Ribera county in Valencia (Spain) older than 97 years old and who accepted to participate in the study. Controls were from the same poblational base, chosen randomly, and 70-80 years old. We made a descriptive analysis of sociodemographic, clinic and functional variables; an odds ratio (OR) estimation of being centenarian by OP and MDA quartiles; and a tendency analysis by Mantel-Haenszel test.Twenty eight cases and 31 controls were included. Functional state and robust percentage were worse in cases. MDA (1,44±0,45 vs 1,84±0,59, p=0,005), and OP (64,29±15,73 vs. 76,52±13,44, p=0,002) levels, were significantly lower in cases. The OR of being centenarian in lower/higher quartile were 3,8 for MDA and 5,7 for OP, with a Mantel-Haenszel signification of 0,029 and 0,044 respectively.In our study OE level were lower in centenarians than in younger elderly, and the lower the OE grade, the higher were the likelihood of being centenarian.

There are few systematic studies on the prevalence of sarcopenia using the new diagnostic criteria in different geriatric care settings.To estimate the prevalence of sarcopenia, using the European Working Group on Sarcopenia in Older People (EWGSOP) criteria in older subjects living in nursing homes and in those who attend geriatric outpatient clinics.A single country multicentre study in two samples of older subjects: patients cared for in outpatient geriatric clinics, and individuals living in nursing homes. Data collected will include demographic variables, medical history, medication, geriatric syndromes, functional status (assessment of basic and instrumental activities of daily living), mobility, cognitive status, comorbidity, quality of life, nutritional status, and laboratory parameters. For the diagnosis of sarcopenia, 4m walking speed, handgrip strength, and body composition measured by bioelectrical impedance analysis will be assessed.Using the EWGSOP algorithm, the prevalence of sarcopenia in an elderly Spanish population will be estimated. In addition, concordance and correlation between the three parameters included in the definition (muscle mass, muscle strength, and physical performance) will be analysed, using the different existing cut-off points, and examining the diagnostic accuracy of each. Finally, demographic, anthropometric and functional data that define subjects with sarcopenia will be investigated.The ELLI study should improve knowledge on the prevalence and characteristics of sarcopenia in older people in our population.

The beneficial effects of physical exercise, in both the treatment and the prevention of several diseases, have been extensively demonstrated. The most common dementia, Alzheimer's disease (AD), is a disorder in which exercise induces significant improvement at pathophysiopathological and cognitive levels. In the present work, we studied the relationship between physical exercise, oxidative stress, and cognition in the double transgenic mice model (2×Tg) for AD, APP/PSN1. This model is mainly based on the cerebral deposition of amyloid β plaques.Eighteen ten-month-old mice were divided into four experimental groups: exercised 2×Tg (2×Tg-E) (n=5), rested 2×Tg (2×Tg-R) (n=5), exercised controls (control-E) (n=4) and rested controls (control-R) (n=4). We trained the animals for twelve weeks with a combination of forced exercise (treadmill running three days/week) and spontaneous wheel running. The animals were evaluated with physical and cognitive tests before and after the training period. We analyzed systemic and cortical oxidative damage and the induction of antioxidant enzymes.The 2×Tg-R mice showed a decrease in their grip strength and VO(2max) as they grew older which was prevented by training. The 2×Tg-E group showed better memory than the 2×Tg-R animals. All the trained groups demonstrated greater exploratory capacity and less anxiety than the sedentary animals. Systemic oxidative damage was slightly decreased in the 2×Tg, although we found no difference in the lipoperoxidation and in the induction of the antioxidant defense in cortex between groups.Physical exercise leads to improvements in the grip strength, VO(2max), cognition, and memory in 2×Tg mice. These improvements are not significantly related to changes in the antioxidant defenses or a reduction in the oxidative damage brought about by exercise.

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.