Susana Rodríguez-González

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.

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

Abstract:  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 β‐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.

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.

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

Eur J Clin Invest 2012; 42 (10): 1037–1046

Overweight in elderly people induces impaired autophagy in skeletal muscle

Abstract 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. Graphical abstract Figure. No caption available. HighlightsOverweight induces oxidative and endoplasmic reticulum stress in the elderly.Aging aggravates overweight effect on human skeletal muscle.Overweight forces the aged muscle to increase requirements from autophagy mechanisms.Impaired autophagy could be the main reason of myogenesis dysfunction during aging.Overweight seems to promote pro‐inflammatory instead of anti‐inflammatory response.

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.

Autophagic and proteolytic processes in the Harderian gland are modulated during the estrous cycle

The Syrian hamster Harderian gland (HG) is an organ that undergoes physiological autophagy in response to oxidative stress induced by porphyrin production. Porphyrin production in the HG has marked sex differences and is closely linked to reproductive function. In the present study, we observed that the estrous cycle and associated estrogen variations may affect oxidative-stress-induced proteolytic processes. In particular, significant changes in autophagic activity were detected during the estrous cycle. Notably, increased activation of macroautophagy as well as chaperone-mediated autophagy in the estrus phase coincided with a minimal antioxidant capability and the highest protein damage levels. By contrast, autophagic machinery was found to be blocked in the diestrus phase, likely due to mammalian target of rapamycin activation, which could be corroborated by the subsequent pS6K activation. Analogous results were observed regarding proteasome activity, which also showed maximal activity in the estrus phase. Interestingly, all these mechanisms were associated with important morphological changes in the HG during the estrous cycle. We observed statistically significant increases in Type II cells, which may be related to extensive autophagy in the estrus phase. Physiologically, this would result in a significant release of porphyrins specifically when females are more receptive. These data support the role of porphyrins as pheromones, as other authors have previously suggested, thus making the HG a scent organ. In addition, these results suggest a porphyrin-based approach to the treatment of porphyria during pregnancy, a condition for which no treatment is currently known.

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.

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.

¿Pueden ser la interleucina-2 y la interleucina-1β biomarcadores específicos

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-1β, 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-1β 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-1β is not specific to this dimension as it also predicts severity of general and global symptomatology.