Muscle Hypertrophy Is Linked to Changes in the Oxidative and Proteolytic Systems during Early Tenderization of the Spanish Breed "Asturiana de los Valles".

For fresh meat consumers, eating satisfaction is of utmost importance and tenderness is one of the most important characteristics in this regard. Our study examined beef of different animal biotypes of the autochthonous breed "Asturiana de los Valles" (AV) to determine if early postmortem oxidative and proteolytic processes may influence the final tenderness of the product. This meat-specialized breed shows different biotypes depending on the frequency of a myostatin mutation "mh" that induces double-muscling or muscular hypertrophy (mh/mh, mh/+, +/+). Samples from the longissimus dorsi muscles of yearling bulls were analyzed during the first 24 h postmortem. Changes in the redox balance of muscle cells were significant in the first hours after slaughter; total antioxidant activity was higher in the mh/mh biotype and it followed the shortening of the sarcomeres, a key parameter in understanding meat tenderness. The two proteolytic systems studied (proteasome and lysosome) followed distinct patterns. Proteasome activity was higher in the (mh/+) biotype, which correlated with higher protein damage. Lysosome proteolysis was increased in the more tender biotypes (mh genotypes). Autophagic activation showed significant differences between the biotypes, with (mh/mh) showing more intense basal autophagy at the beginning of the postmortem period that decreased gradually (p < 0.001), while in the normal biotype (+/+), it was slightly delayed and then increased progressively (p < 0.001). These results suggest that this type of catalytic process and antioxidant activity could contribute to the earlier disintegration of the myofibers, particularly in the mh/mh biotypes, and influence the conversion of muscle into meat.

Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model.

Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.

Selective autophagy, lipophagy and mitophagy, in the Harderian gland along the oestrous cycle: a potential retrieval effect of melatonin.

Sexual dimorphism has been reported in many processes. However, sexual bias in favour of the use of males is very present in science. One of the main reasons is that the impact of hormones in diverse pathways and processes such as autophagy have not been properly addressed in vivo. The Harderian gland is a perfect model to study autophagic modulation as it exhibits important changes during the oestrous cycle. The aim of this study is to identify the main processes behind Harderian gland differences under oestrous cycle and their modulator. In the present study we show that redox-sensitive transcription factors have an essential role: NF-κB may activate SQSTM1/p62 in oestrus, promoting selective types of autophagy: mitophagy and lipophagy. Nrf2 activation in dioestrus, leads the retrieval phase and restoration of mitochondrial homeostasis. Melatonin's receptors show higher expression in dioestrus, leading to decreases in pro-inflammatory mediators and enhanced Nrf2 expression. Consequently, autophagy is blocked, and porphyrin release is reduced. All these results point to melatonin as one of the main modulators of the changes in autophagy during the oestrous cycle.

Increased serum strontium levels and altered oxidative stress status in early-onset preeclampsia.

BACKGROUND: Correctly distinguishing preeclampsia (PE), gestational hypertension (GH), and intrauterine growth retardation (IUGR) is a challenge for clinicians due to existing similarities. In our previous study, we showed that serum strontium (Sr) levels were elevated in preeclamptic women compared to healthy and GH pregnant women at the end of pregnancy. The main aim of this study was to evaluate Sr and oxidative stress in PE at the time of symptoms onset and before and compare it with IUGR/GH. METHODS: Samples collected at symptoms onset included 77 preeclamptic women and 72 women diagnosed with IUGR/GH divided into two groups according to the gestational extraction week (<34 and ≥ 34). Fifteen patients were also serialized until delivery. Samples collected before symptoms onset included 140 women who developed early-onset PE (E-PE, n = 9), late-onset PE (L-PE, n = 13), IUGR (n = 9), GH (n = 32) and no pathologies (n = 77). Strontium, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), uric acid (UA), creatinine, lipid peroxidation, and total antioxidant activity (TAA) were measured. RESULTS: Mean Sr, sFlt-1/PIGF ratio, UA, and lipid peroxidation/TAA ratio levels were significantly higher (p = 0.002, <0.0001, <0.0001 and = 0.03, respectively) and estimated glomerular filtration rate (eGFR) and TAA significantly lower (p = 0.0008 and < 0.0001, respectively) in E-PE vs other pathologies when gestational extraction week was <34. There was a significant correlation between Sr and eGFR (r = 0.43, p = 0.02), sFlt-1/PIGF ratio (r = 0.56, p = 0.002), TAA and gestational week of sampling (r = -0.45, p = 0.02) and UA (r = -0.82, p < 0.0001) in the E-PE serial samples. No differences were found in Sr levels before symptoms onset. CONCLUSION: Serum Sr concentration and oxidative status are increased in E-PE when compared to other pathologies at the time of symptoms onset. More studies are needed to elucidate the causes of Sr levels elevation and its role in the pathophysiology of PE.

¿Pueden ser la interleucina-2 y la interleucina-1ß biomarcadores específicos de la sintomatología negativa en la esquizofrenia? / Can interleukin-2 and interleukin-1ß be specific biomarkers of negative symptoms in schizophrenia?

Introducción: Hay evidencias que sugieren la existencia de alteraciones de algunas citocinas en pacientes con esquizofrenia, pero su asociación con la psicopatología aún no está clara. El objetivo de este estudio es determinar si los niveles de citocinas proinflamatorias (factor de necrosis tumoral-alfa, interleucina [IL]-6, IL-2, IL-1ß, IL-1RA) están aumentados en pacientes ambulatorios clínicamente estables en comparación con individuos sanos, y analizar si podrían ser biomarcadores específicos de las diferentes dimensiones clínicas de la esquizofrenia. Métodos: Se evaluaron 73 pacientes con esquizofrenia en sus primeros 10 años de evolución de la enfermedad y 73 controles sanos pareados por edad y sexo. Se realizó una evaluación precisa de las dimensiones clínicas (positiva, negativa, depresiva y cognitiva) en estos pacientes. Resultados: Solo los niveles de IL-6 están significativamente elevados en los pacientes tras controlar por índice de masa corporal, perímetro abdominal, tabaquismo y tratamiento psicofarmacológico en comparación con sus controles sanos. Tras ajustar por varios factores de confusión, los modelos de regresión lineal múltiple identificaron cómo las concentraciones de IL-1ß predicen los síntomas negativos, psicopatología general y gravedad global de la Escala del Síndrome Positivo y Negativo, mientras los niveles de IL-2 predicen el dominio motivación y placer de la Entrevista de Evaluación Clínica para Síntomas Negativos y la puntuación global en la Escala de Funcionamiento Personal y Social. Sin embargo, el rendimiento cognitivo, la gravedad de los síntomas depresivos y positivos no correlacionaron con ninguna de las citocinas. Conclusiones: Nuestros hallazgos sugieren que las concentraciones de IL-6 permanecen elevadas en pacientes estables con esquizofrenia. Mientras que la IL-2 marca específicamente la gravedad en el dominio motivación y placer de la sintomatología negativa, la IL-1ß no es específica para esta dimensión, ya que también predice la gravedad de la sintomatología general y global

Introduction: Evidence suggests the existence of cytokine disturbances in patients with schizophrenia but their association with psychopathology is still unclear. The aim of the current study was to determine if pro-inflammatory cytokine levels (tumor necrosis factor-alfa, interleukin (IL)-6, IL-2, IL-1ß, IL-1RA) are increased in stable outpatients compared with healthy subjects, and to analyze if they could be specific biomarkers of clinical dimensions in schizophrenia. Methods: We studied 73 stable outpatients with schizophrenia in their first 10 years of illness and 73 age- and sex-matched healthy controls. An accurate assessment of clinical dimensions (positive, negative, depressive, cognitive) was performed in patients. Results: Only IL-6 levels were significantly increased in patients after controlling for body mass index, waist circumference, smoking, and psychopharmacological treatment, compared with healthy subjects. After adjusting for several confounders, multiple linear regression models identified that Positive and Negative Syndrome Scale negative symptoms, general psychopathology, and global severity are predicted by IL-1ß concentrations, while motivation and pleasure domain of Clinical Assessment Interview for Negative Symptoms and Personal and Social Performance global functioning scores are predicted by IL-2 levels. Cognitive performance, positive, and depressive symptom severity did not correlate with any cytokine. Conclusions: Our findings suggested that IL-6 concentrations are elevated in stable patients with schizophrenia. Whereas IL-2 specifically marks severity of the motivation and pleasure domain of negative symptoms, IL-1ß is not specific to this dimension as it also predicts severity of general and global symptomatology

Can interleukin-2 and interleukin-1ß be specific biomarkers of negative symptoms in schizophrenia? / ¿Pueden ser la interleucina-2 y la interleucina-1ß biomarcadores específicos de la sintomatología negativa en la esquizofrenia?

INTRODUCTION: Evidence suggests the existence of cytokine disturbances in patients with schizophrenia but their association with psychopathology is still unclear. The aim of the current study was to determine if pro-inflammatory cytokine levels (tumor necrosis factor-α, interleukin (IL)-6, IL-2, IL-1ß, IL-1RA) are increased in stable outpatients compared with healthy subjects, and to analyze if they could be specific biomarkers of clinical dimensions in schizophrenia. METHODS: We studied 73 stable outpatients with schizophrenia in their first 10 years of illness and 73 age- and sex-matched healthy controls. An accurate assessment of clinical dimensions (positive, negative, depressive, cognitive) was performed in patients. RESULTS: Only IL-6 levels were significantly increased in patients after controlling for body mass index, waist circumference, smoking, and psychopharmacological treatment, compared with healthy subjects. After adjusting for several confounders, multiple linear regression models identified that Positive and Negative Syndrome Scale negative symptoms, general psychopathology, and global severity are predicted by IL-1ß concentrations, while motivation and pleasure domain of Clinical Assessment Interview for Negative Symptoms and Personal and Social Performance global functioning scores are predicted by IL-2 levels. Cognitive performance, positive, and depressive symptom severity did not correlate with any cytokine. CONCLUSIONS: Our findings suggested that IL-6 concentrations are elevated in stable patients with schizophrenia. Whereas IL-2 specifically marks severity of the motivation and pleasure domain of negative symptoms, IL-1ß is not specific to this dimension as it also predicts severity of general and global symptomatology.

Biomarcadores de estrés oxidativo y dimensiones clínicas en los 10 primeros años de esquizofrenia / Oxidative stress biomarkers and clinical dimensions in first 10 years of schizophrenia

Introducción: Diversos estudios han encontrado un aumento de los parámetros de estrés oxidativo en pacientes con esquizofrenia. Los objetivos de este estudio han sido identificar potenciales biomarcadores de estrés oxidativo en pacientes con esquizofrenia estables, durante los primeros 10 años de enfermedad, y determinar si se asocian con dimensiones clínicas específicas. Material y métodos: Se evaluaron 73 pacientes clínicamente estables y 73 controles sanos pareados por edad y sexo. Se recogieron datos sociodemográficos, clínicos y parámetros biológicos. Los biomarcadores sanguíneos incluyeron homocisteína, porcentaje de hemólisis, subproductos de peroxidación lipídica y, como biomarcador antioxidante, actividad de la catalasa en eritrocitos. Resultados: Los análisis comparativos tras controlar por tabaquismo y síndrome metabólico evidenciaron un aumento significativo en la actividad de la catalasa en pacientes. Asimismo, niveles inferiores de peroxidación lipídica se asociaron de manera significativa con la sintomatología negativa. Conclusiones: Como conclusión, los mecanismos compensatorios antioxidantes podrían estar aumentados en pacientes con esquizofrenia estables durante las fases iniciales. Además, podría existir una relación inversa entre el estrés oxidativo y la dimensión negativa

Introduction: Several studies have described increased oxidative stress parameters in patients with schizophrenia. The objectives of the current study were to identify potential oxidative stress biomarkers in stable patients during first 10 years of schizophrenia and determine if they are associated with specific clinical dimensions. Material and methods: Seventy-three clinically stable outpatients with schizophrenia and 73 sex and age-matched healthy controls were recruited. Sociodemographic, clinical and biological data were collected at enrollment. Blood biomarkers included homocysteine, the percentage of hemolysis, lipid peroxidation subproducts, and as an antioxidant biomarker, catalase activity in erythrocytes. Results: Comparative analyses after controlling for smoking and metabolic syndrome evidenced a significant increase in catalase activity in patients. Also, lower lipid peroxidation levels showed an association with negative symptoms. Conclusions: In conclusion, compensatory antioxidant mechanisms might be increased in stable patients with schizophrenia at early stages. Furthermore, there may be an inverse relationship between oxidative stress and negative dimension

Oxidative stress biomarkers and clinical dimensions in first 10 years of schizophrenia. / Biomarcadores de estrés oxidativo y dimensiones clínicas en los 10 primeros años de esquizofrenia.

INTRODUCTION: Several studies have described increased oxidative stress parameters in patients with schizophrenia. The objectives of the current study were to identify potential oxidative stress biomarkers in stable patients during first 10 years of schizophrenia and determine if they are associated with specific clinical dimensions. MATERIAL AND METHODS: Seventy-three clinically stable outpatients with schizophrenia and 73 sex and age-matched healthy controls were recruited. Sociodemographic, clinical and biological data were collected at enrollment. Blood biomarkers included homocysteine, the percentage of hemolysis, lipid peroxidation subproducts, and as an antioxidant biomarker, catalase activity in erythrocytes. RESULTS: Comparative analyses after controlling for smoking and metabolic syndrome evidenced a significant increase in catalase activity in patients. Also, lower lipid peroxidation levels showed an association with negative symptoms. CONCLUSIONS: In conclusion, compensatory antioxidant mechanisms might be increased in stable patients with schizophrenia at early stages. Furthermore, there may be an inverse relationship between oxidative stress and negative dimension.

Strontium and its role in preeclampsia.

BACKGROUND: Preeclampsia (PE) is considered a specific vascular disease in which endothelial dysfunction may be the crucial factor of its pathogenesis. It has been suggested that strontium (Sr) may play a role in the pathophysiology of PE. Our group established in a previous study the serum levels of Sr in healthy pregnancies, and the main aim of the present study was to evaluate Sr concentrations and oxidative status in preeclamptic women. METHODS: The study population included women with early-onset PE (E-PE, n = 39), late-onset PE (L-PE, n = 67) and serial samples from a subset of preeclamptic women (PE-ss, n = 20). The control group included women with gestational hypertension (GH, n = 56) and healthy pregnancies (samples collected in the 1st (n = 50), 2nd (n = 51) and 3rd trimesters (n = 53)). Strontium, calcium (Ca), uric acid (UA), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), lipid peroxidation and total antioxidant activity (TAA) were measured in these samples. RESULTS: Mean Sr levels were significantly higher in PE than in control groups (p ≤ 0.0001). Calcium values were found to be significantly lower in E-PE compared to control groups (p = 0.03). Higher levels of NT-proBNP were found in PE vs. control groups (p < 0.001). sFlt-1/PlGF ratio was higher in E-PE compared to L-PE and GH (p < 0.001). Uric acid levels in PE were significantly higher than in control groups (p < 0.0001). There was a strong positive correlation between UA and Sr in the E-PE serial samples (r = 0.80, p < 0.0001). Lipid peroxidation and lipid peroxidation/TAA ratios were found to be higher in PE, with lower values of TAA. CONCLUSION: The higher levels of Sr and the alterations of redox status found in preeclamptic women, along with the strong correlation between UA and Sr suggest that this element may be involved in the pathogenesis of PE.

Strontium and oxidative stress in normal pregnancy.

BACKGROUND: Pregnancy brings about metabolic and oxidative changes that involve various trace elements and oxidative stress. Strontium (Sr) is a trace element scarcely studied in this context, although it has been suggested that it may play a role in the pathophysiology of preeclampsia. The main aim of this study was to evaluate Sr concentrations and oxidative status in normal pregnancy. METHODS: The study population included non-pregnant women (n=31), healthy pregnant women in the first (n=50), second (n=51) and third (n=53) trimesters of gestation, and women in postpartum period (n=31). Additionally, samples from another twenty pregnant women were obtained in the three trimesters. Strontium, copper, selenium and zinc were measured by inductively coupled plasma-mass spectrometry. Calcium (Ca), uric acid (UA), lipid peroxidation and total antioxidant activity (TAA) were measured by spectrophotometric assays. RESULTS: Strontium remained unchanged until the third trimester of pregnancy, in which significantly higher levels were found (p=0.001). The other elements showed diverse trends during pregnancy. Uric acid levels were significantly different in all groups (p<0.001), increasing gradually as the pregnancy progresses. In serial samples, there was a statistically significant positive correlation between Sr and gestational week of sampling (r=0.31, p=0.01), UA (r=0.40, p=0.001) and lipid peroxidation/TAA ratio (r=0.38, p=0.0002). Additionally, Sr correlated negatively with TAA (r=-0.40, p=0.0001). CONCLUSION: Strontium seems to play a physiological role in the oxidative status of the human organism. Further studies involving Sr and pathologies of pregnancy are warranted.

Overweight in elderly people induces impaired autophagy in skeletal muscle.

Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases.

Autophagy during beef aging.

The conversion of muscle into meat is a complex process of major concern for meat scientists due to its influence on the final meat quality. The aim of this study was to investigate the occurrence of autophagic processes in the conversion of muscle into meat. Our findings demonstrated, for the first time, the occurrence of autophagic processes in the muscle tissue at early postmortem period (2 h to 24 h) in both beef breeds studied (Asturiana de los Valles and Asturiana de la Montaña) showing significant time-scale differences between breeds, which could indicate a role of this process in meat maturation. These breeds have different physiological features: while Asturiana de los Valles is a meat-specialized breed showing high growth rate, an elevated proportion of white fibers in the muscle and low intramuscular fat level, Asturiana de la Montaña is a small- to medium-sized rustic breed adapted to less-favored areas, showing more red fibers in the muscle and a high intramuscular fat content.

Chronic training increases blood oxidative damage but promotes health in elderly men.

The objective of the present study was to investigate a large panel of oxidative stress biomarkers in long-term trained elderly men to analyse the effects of chronic training on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during middle age (mean training time=49 ± 8 years). We studied morbidity and polypharmacy, as well as haematological parameters including red cell count, haemoglobin concentration, haematocrit, mean corpuscular volume, red cell distribution width and several oxidative biomarkers including protein carbonyl content and lipid peroxidation in plasma and erythrocytes, red blood cell H2O2-induced haemolysis test, plasma total antioxidant activity and the main antioxidant enzymes of erythrocytes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. After adjusting for confounding factors, we observed an increase in all oxidative damage biomarkers in the plasma and erythrocytes of the long-term exercise group. However, we reported a decrease in the number of diseases per subject with statistical differences nearly significant (p=0.061), reduced intake of medications per subject and lower levels of red cell distribution width in the chronic exercise group. These results indicate that chronic exercise from middle age to old age increases oxidative damage; however, chronic exercise appears to be an effective strategy to attenuate the age-related decline in the elderly.

Inicios de la enfermería militar en la aviación militar española / Início do enfemería militar na aviação militar espanhola / Beginning of military nursing in the Spanish military aviation

Se ha recordado en 2011 el centenario de la aviación militar española, al considerarse 1911 como el año que marca su inicio. El objetivo de este trabajo ha sido presentar a los primeros profesionales de enfermería militares que desempeñaron su cometido en la atención al personal de la aviación militar española. En el desarrollo del trabajo se ha tratado de conformar un relato historiográfico básico que entrelazara la evolución de la enfermería y la aviación militar en España, documentando los primeros profesionales de enfermería militares en unidades de aviación en 1928 (AU)

2011 marks the first century of the Spanish military aviation, since 1911 is considered its initial year. The objective of this study is to present the first military nursing professionals that carried out their jobs in the health care of the early Spanish Air Force. The development of this study presents a basic historiographic story, linking the evolutions of health care and the Spanish military aviation, and covering the early professionals of nursing in aviation units back in 1928 (AU)

O ano 2011marca o centenário da aviação militar espanhola, sendo considerado1911 como o ano que marcao seu início. O objetivo deste trabalho foia presentara os primeiros profissionais da enfermagem militar que fizeram da sua profissão a atenção continuada da saude do pessoal da aviação militar espanhola. O desenvolvimento do trabalho tenta fazer uma narraçao historiográfica que entrelaça a evolução da enfermageme da aviação militar em Espanha, e que documenta os primeiros profissionais da enfermagem militar nas unidades da aviação em 1928 (AU)

Chronic inflammation as predictor of 1-year hospitalization and mortality in elderly population.

BACKGROUND: Systemic low-grade inflammation is thought to be associated with an increased risk of adverse clinical outcomes in elderly population. We tested this notion with the goal of identifying useful potential biomarkers of 1-year hospitalization and mortality in the elderly population. DESIGN: A total of 120 institutionalized older subjects were enrolled as participants in this study, including 90 women and 30 men (ranging in age from 68 to 105 years), selected from Santa Teresa nursing home (Oviedo, Spain). We studied functional status, morbidity, socio-demographic characteristics and several inflammation and inflammation-related markers. RESULTS: The study included 95 non-hospitalized participants and 23 participants with at least one hospitalization during 1 year (19% of subjects). The study also included 100 survivors and 19 participants who died during the 1-year study (16% of subjects). In logistic regression models adjusted by age, sex, anti-inflammatory drug use and morbid conditions, high levels of interleukin 1 receptor antagonist (IL-1ra) and red blood cell distribution width (RDW) were associated with hospitalization and death at 1 year. Elevated levels of tumour necrosis factor α (TNF-α) were also associated with an increased risk of death at 1 year after adjusting for the same potential confounders. Multivariate logistic regression models showed that elevated serum levels of IL-1ra were intimately associated with 1-year subsequent hospitalization and mortality in aged subjects after adjusting for age, sex, anti-inflammatory drug use and morbid conditions. CONCLUSIONS: Current data suggest that IL-1ra is a predictor of 1-year hospitalization and mortality in the elderly population.

Interleukin 6, soluble tumor necrosis factor receptor I and red blood cell distribution width as biological markers of functional dependence in an elderly population: a translational approach.

In the present investigation we have analyzed the association between functional dependence and inflammatory biomarkers using the Barthel Index (BI) and the Katz Index (KI). This analysis may contribute to translational medicine by incorporating the clinical and laboratory data to better understand the relationship between chronic inflammation and functional dependence in the elderly population. The ultimate goal of this study was to identify possible useful biomarkers of functional dependence in the elderly. Participants in this study consisted of 120 older subjects (90 women and 30 men; range 68-105 years) who were selected from the Santa Teresa nursing home (Oviedo, Spain). We studied functional status using the following tools to diagnose the functional dependence by clinicians: BI and KI for activities of daily living. We analyzed morbidity, sociodemographic characteristics and a panel of inflammatory and inflammatory-related markers. In linear regression models adjusted by age, sex, anti-inflammatory drug use and morbid conditions high levels of interleukin 6 (IL-6) and soluble TNF receptor-I (sTNF-RI) were associated with functional dependence as measured using BI and KI. Elevated levels of red blood cell distribution width (RDW) were also associated with functional dependence measured using the KI after adjusting for the same potential confounders. The current results suggest that high IL-6, sTNF-RI and RDW levels are associated with the functional dependence in the elderly population. The results are consistent with the presumed underlying biological mechanism, in which the up-regulation of inflammatory mediators is associated with functional dependence in elderly subjects.

Oxidative protein damage is associated with severe functional dependence among the elderly population: a principal component analysis approach.

BACKGROUND: Studies of the role of oxidative stress in functional dependence among the aging population are limited. In this report, we address this situation through an analysis of a large panel of blood oxidative biomarkers in elderly population. Because the analysis of multiple biomarkers increases the complexity of data interpretation, this investigation has utilized both an analysis of single biomarkers in addition to employment of the statistical data reduction tool principal component analysis that might allow for a clearer description of redox status as compared with a single measure alone. METHODS: We studied three groups of participants older than 65 years based on their Barthel Index: an independent group (100-95), a moderately dependent group (94-60), and a severely dependent group (59-0). RESULTS: We observed a significant increase in circulating protein carbonyl levels in the severely dependent group as compared with the independent and moderately dependent groups. Using principal component analysis, we found at least three factors (an erythrocyte-related component, a protein damage-related component, and a plasma-related component) that could be used to assess the different oxidative parameters in our population. We discovered a significant association of higher levels of the protein damage-related component with the severely dependent group. CONCLUSIONS: Protein damage levels could be assessed in clinical use as a biomarker of severe dependence. Furthermore, our results support the hypothesis that functional decline could be associated in part due to oxidative stress. Finally, we show that principal component analysis could be a useful statistical tool in the analysis of age-related decline.

Long-term training induces a healthy inflammatory and endocrine emergent biomarker profile in elderly men.

The objective of the present study was to investigate the changes in a large panel of emergent geriatric biomarkers in long-term trained elderly men to analyze the effects of long-term exercise on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during adulthood (mean training time = 49 ± 8 years). We studied morbidity, polypharmacy, cellular and serological inflammatory parameters, and endocrine mediators. After adjusting for confounding factors, we observed reduced medication intake per subject and lower number of diseases per subject with statistical differences nearly significant in the long-term exercise group. We showed that long-term training was associated with lower levels of white blood cell counts, neutrophil counts, interleukin-6, interleukin-10, interleukin-1 receptor antagonist, and soluble TNF receptor-I. Furthermore, we noted an increase in the concentrations of insulin-like growth factor-1 and dehydroepiandrosterone in the long-term training group. We concluded that long-term exercise training from adulthood to old age is clearly associated with a healthy profile of emergent geriatric biomarkers. Long-term training could improve the inflammatory-endocrine imbalance associated with disease, frailty, functional decline, and mortality in elderly men. Our results point to the benefits of prolonged exercise from adulthood to old age.

Melatonin induces neural SOD2 expression independent of the NF-kappaB pathway and improves the mitochondrial population and function in old mice.

Aging is commonly defined as a physiological phenomenon associated with morphological and functional deleterious changes in which oxidative stress has a fundamental impact; therefore, readjusting the oxidative balance should have beneficial effects. In our study, we tested the antioxidant melatonin in old mouse brains and showed positive effects at the cellular and mitochondrial levels. Melatonin attenuated ß-amyloid protein expression and α-synuclein deposits in the brain compared to aged group. Furthermore, oxidative stress was increased by aging and induced the nuclear translocation of nuclear factor-kappa B (NF-κB), which was suppressed by melatonin treatment. The antioxidant mitochondrial expression, superoxide dismutase 2 (SOD2), was increased in both control and melatonin-treated old mice, despite the different activation states of the NF-κB pathway. The NF-κB pathway was activated in the old mice, which may be explained by this group's response to the increased oxidative insult; this insult was inhibited in melatonin-treated animals, showing this group an increase in active mitochondria population that was not observed in old group. We also report that melatonin is capable of restoring the mitochondrial potential of age-damaged neurons. In conclusion, melatonin's beneficial effects on brain aging are linked to the increase in mitochondrial membrane potential and SOD2 expression, which probably reduces the mitochondrial contribution to the oxidative stress imbalance.