Publications by authors named "Carmen Vida"

31 Publications

The Immunity Clock.

J Gerontol A Biol Sci Med Sci 2021 May 12. Epub 2021 May 12.

Department of Genetics, Physiology and Microbiology (Unity of Animal Physiology), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain.

The immune system has been for long considered a marker of health. The age-related decline in its function results in a greater incidence of infections, autoimmune diseases and cancer. Nevertheless, it is still not known if immune function can be used to accurately estimate the rate of aging of an individual. A set of 14 immune function variables were measured in 214 healthy individuals ranging from 19 to 88 years old. All immune variables were selected as independent variables for the prediction of age by multiple linear regression (MLR). The Immunity Clock was constructed including the following 5 immune variables: natural killer activity, phagocytosis and chemotaxis of neutrophils and chemotaxis and proliferative capacity of lymphocytes reaching an adjusted R 2 of 80.3% and a standard error of the estimate of 4.74 years. The Immunity Clock was validated in a different group of healthy individuals (N=106) obtaining a Pearson´s correlation coefficient of 0.898 (p < 0.001) between chronological age and the age estimated by the Immunity Clock, the ImmunolAge. Moreover, we demonstrate that women with anxiety (N=10) show a higher ImmunolAge than their chronological age whereas healthy centenarians (N=8) show a lower one. In addition, the Immunity Clock provided here proves to be useful for monitoring the effectiveness of a nutritional intervention lasting one month, by detecting a diminished ImmunolAge in the same individuals. Further research will be needed to ascertain if the Immunity Clock is a passive marker of the aging process or it plays an active role in it.
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http://dx.doi.org/10.1093/gerona/glab136DOI Listing
May 2021

A high magnesium concentration in citrate dialysate prevents oxidative stress and damage in human monocytes .

Clin Kidney J 2021 May 30;14(5):1403-1411. Epub 2020 Aug 30.

Dpto de Biología de Sistemas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.

Background: The use of dialysis fluids (DFs) during haemodialysis has been associated with increased oxidative stress and reduced serum magnesium (Mg) levels, contributing to chronic inflammation. Since the role of Mg in modulating immune function and reducing oxidative stress has been demonstrated, the aim of this study was to characterize whether increasing the Mg concentration in DFs could protect immune cells from oxidative stress and damage.

Methods: The effect of citrate [citrate dialysis fluid (CDF), 1 mM] or acetate [acetate dialysis fluid (ADF), 3 mM] dialysates with low (0.5 mM; routinely used) or high (1 mM, 1.25 mM and 2 mM) Mg concentrations was assessed in THP-1 human monocytes. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized/reduced (GSSG/GSH) glutathione were quantified under basal and inflammatory conditions (stimulation with lipopolysaccharide, LPS).

Results: The increase of Mg in CDF resulted in a significant reduction of ROS production under basal and inflammatory conditions (extremely marked in 2 mM Mg; P 0.001). These effects were not observed in ADF. Interestingly, in a dose-dependent manner, high Mg doses in CDF reduced oxidative stress in monocytes under both basal and inflammatory conditions. In fact, 2 mM Mg significantly decreased the levels of GSH, GSSG and MDA and the GSSG/GSH ratio in relation to 0.5 mM Mg.

Conclusions: CDF produces lower oxidative stress than ADF. The increase of Mg content in DFs, especially in CDF, could have a positive and protective effect in reducing oxidative stress and damage in immune cells, especially under inflammatory conditions.
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http://dx.doi.org/10.1093/ckj/sfaa131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087128PMC
May 2021

Ontogeny of leukocyte profiles in a wild altricial passerine.

J Comp Physiol B 2021 Jan 16;191(1):195-206. Epub 2020 Nov 16.

Instituto de Investigación en Recursos Cinegéticos, IREC (CSIC, UCLM, JCCM), Ronda de Toledo 12, 13005, Ciudad Real, Spain.

Ecophysiological studies have highlighted the relevance of the avian immune system in individual fitness prospects in the wild. However, studies on the ontogeny of avian immunity are scarce. We analyse age-related changes in the cellular constitutive immunity throughout nestling development, as well as its relationship with sex and brood size. We found that cellular constitutive immunity could be affected by age, sex, brood size, or daily rhythm. Early-stage nestlings relied more on cells of the innate immunity rather than on cells linked to the adaptive immune system. Cellular immunity may not be fully mature in fledglings, as reflected by differences in phagocytic cell counts with regard to adults. Beyond the age-dependent effects, agranulocyte cell counts were affected by sibling competition while granulocyte cell counts showed a daily rhythm. We also show that the heterophil to lymphocyte ratio was negatively related to body weight when nestlings become more independent. Our study contributes knowledge to the fields of developmental immunology and ecological immunology based on essential components of the cellular immune system.
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http://dx.doi.org/10.1007/s00360-020-01323-zDOI Listing
January 2021

Soil Application of a Formulated Biocontrol Rhizobacterium, PCL1606, Induces Soil Suppressiveness by Impacting Specific Microbial Communities.

Front Microbiol 2020 7;11:1874. Epub 2020 Aug 7.

Departamento de Microbiología, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain.

Biocontrol bacteria can be used for plant protection against some plant diseases. PCL1606 (PcPCL1606) is a model bacterium isolated from the avocado rhizosphere with strong antifungal antagonism mediated by the production of 2-hexyl, 5-propil resorcinol (HPR). Additionally, PcPCL1606 has biological control against different soil-borne fungal pathogens, including the causal agent of the white root rot of many woody crops and avocado in the Mediterranean area, . The objective of this study was to assess whether the semicommercial application of PcPCL1606 to soil can potentially affect avocado soil and rhizosphere microbial communities and their activities in natural conditions and under infection. To test the putative effects of PcPCL1606 on soil eukaryotic and prokaryotic communities, a formulated PcPCL1606 was prepared and applied to the soil of avocado plants growing in mesocosm experiments, and the communities were analyzed by using 16S/ITS metagenomics. PcPCL1606 survived until the end of the experiments. The effect of PcPCL1606 application on prokaryotic communities in soil and rhizosphere samples from natural soil was not detectable, and very minor changes were observed in eukaryotic communities. In the infested soils, the presence of strongly impacted the soil and rhizosphere microbial communities. However, after PcPCL1606 was applied to soil infested with , the prokaryotic community reacted by increasing the relative abundance of few families with protective features against fungal soilborne pathogens and organic matter decomposition (, ), but no new prokaryotic families were detected. The treatment of PcPCL1606 impacted the fungal profile, which strongly reduced the presence of in avocado soil and rhizosphere, minimizing its effect on the rest of the microbial communities. The bacterial treatment of formulated PcPCL1606 on avocado soils infested with resulted in biological control of the pathogen. This suppressiveness phenotype was analyzed, and PcPCL1606 has a key role in suppressiveness induction; in addition, this phenotype was strongly dependent on the production of HPR.
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http://dx.doi.org/10.3389/fmicb.2020.01874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426498PMC
August 2020

Increasing the Magnesium Concentration in Various Dialysate Solutions Differentially Modulates Oxidative Stress in a Human Monocyte Cell Line.

Antioxidants (Basel) 2020 Apr 15;9(4). Epub 2020 Apr 15.

Departamento de Biología de Sistemas, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Oxidative stress is exacerbated in hemodialysis patients by several factors, including the uremic environment and the use of dialysis fluids (DFs) Since magnesium (Mg) plays a key role in modulating immune function and in reducing oxidative stress, we aimed to evaluate whether increasing the Mg concentration in different DFs could protect against oxidative stress in immunocompetent cells in vitro. Effect of ADF (acetate 3 mM), CDF (citrate 1 mM), and ACDF (citrate 0.8 mM + acetate 0.3 mM) dialysates with Mg at standard (0.5 mM) or higher (1, 1.25, and 2 mM) concentrations were assessed in THP-1 monocyte cultures. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were quantified under basal and uremic conditions (indoxyl sulfate (IS) treatment). Under uremic conditions, the three DFs with 0.5 mM Mg promoted higher ROS production and lipid damage than the control solution. However, CDF and ACDF induced lower levels of ROS and MDA, compared to that induced by ADF. High Mg concentration (1.25 and/or 2 mM) in CDF and ACDF protected against oxidative stress, indicated by reduced ROS and MDA levels compared to respective DFs with standard concentration of Mg. Increasing Mg concentrations in ADF promoted high ROS production and MDA content. Thus, an increase in Mg content in DFs has differential effects on the oxidative stress in IS-treated THP-1 cells depending on the dialysate used.
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http://dx.doi.org/10.3390/antiox9040319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222382PMC
April 2020

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence.

Front Cell Dev Biol 2020 20;8:185. Epub 2020 Mar 20.

Departamento Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud (IRYCIS), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.

Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremia-associated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.
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http://dx.doi.org/10.3389/fcell.2020.00185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099607PMC
March 2020

Immune Function, Oxidative, and Inflammatory Markers in Centenarians as Potential Predictors of Survival and Indicators of Recovery After Hospital Admission.

J Gerontol A Biol Sci Med Sci 2020 09;75(10):1827-1833

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.

Several parameters of immune function, oxidative, and inflammatory stresses have been proposed as markers of health and predictors of longevity and mortality. However, it is unknown if any of these parameters can be used as predictors of survival in centenarians. Therefore, in a group of 27 centenarians, at the time of admission to the Clinical Hospital of Madrid, a series of immune function, antioxidant, oxidant, and inflammatory parameters were studied. Some centenarians survived and others did not, thus establishing two groups, "survivors" (n = 9) and "nonsurvivors" (n = 18). The results show that surviving centenarians display higher neutrophil chemotaxis and microbicidal capacity, natural killer activity, lymphoproliferation, glutathione reductase activity, and basal interleukin-10 release. Moreover, lower neutrophil and lymphocyte adherence, superoxide anion and malondialdehyde concentrations, and basal release of tumor necrosis factor α are also reported. The odds ratios for survival for these parameters were also calculated, with the highest odds ratios being the lymphoproliferative capacity and the ex vivo basal and stimulated release of interleukin-6 from mononuclear cells (odds ratio = 136.00). Therefore, these parameters have the potential to be used in the clinical setting as predictors of survival in centenarians. In the survivors group, the same parameters were also analyzed after 3 months. Because survivors showed an increase in neutrophil and lymphocyte chemotaxis capacity during the recovery period, reaching similar values to those observed in healthy centenarians, these parameters could be proposed as indicators of recovery.
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http://dx.doi.org/10.1093/gerona/glz250DOI Listing
September 2020

High perceived stress in women is linked to oxidation, inflammation and immunosenescence.

Biogerontology 2019 12 8;20(6):823-835. Epub 2019 Aug 8.

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, José Antonio Nováis 12, 28040, Madrid, Spain.

Chronic stress situations lead to an impairment of immune response and higher oxidative and inflammatory stress, which are important underlying mechanisms of the ageing process. However, given that the physiological stress response depends on the subjective appraisal of a given stressor, the aim of the study was to investigate the effect that different degrees of perceived stress have, regardless of their type, on immune functions, oxidative and inflammatory stress and ageing rate of women (30-50 years old). For that purpose, a group of 49 women was classified, according to their scores obtained in the perceived stress scale (PSS), into low (n = 23), moderate (n = 14) and high (n = 12) degree of perceived stress. The immune functions studied were: neutrophil and lymphocyte chemotaxis, neutrophil phagocytic capacity, natural killer activity, lymphoproliferation and LPS-stimulated cytokine release. Basal cytokine release was studied as an inflammatory stress marker. Antioxidant (superoxide dismutase, glutathione peroxidase and reductase activities, and reduced glutathione) and oxidant compounds (oxidized glutathione and malondialdehyde) were also investigated in whole blood as markers of oxidative stress. The results show that, in general, women with a moderate or high degree of perceived stress have a worse immune functionality and higher oxidative and inflammatory stress compared to women with low stress perception. In addition, a positive correlation was found between PSS scores and the biological age of each woman (P ≤ 0.001). In conclusion, high levels of perceived stress in women are associated with a higher oxidative and inflammatory stress and immunosenescence, which seem to accelerate their ageing rate.
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http://dx.doi.org/10.1007/s10522-019-09829-yDOI Listing
December 2019

When will my mouse die? Life span prediction based on immune function, redox and behavioural parameters in female mice at the adult age.

Mech Ageing Dev 2019 09 2;182:111125. Epub 2019 Aug 2.

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain; Institute of Investigation Hospital 12 Octubre, Madrid, Spain. Electronic address:

The identification of predictive markers of life span would help to unravel the underlying mechanisms influencing ageing and longevity. For this aim, 30 variables including immune functions, inflammatory-oxidative stress state and behavioural characteristics were investigated in ICR-CD1 female mice at the adult age (N = 38). Mice were monitored individually until they died and individual life spans were registered. Multiple linear regression was carried out to construct an Immunity model (adjusted R = 75.8%) comprising Macrophage chemotaxis and phagocytosis and Lymphoproliferation capacity, a Redox model (adjusted R = 84.4%) involving Reduced Glutathione and Malondialdehyde concentrations and Glutathione Peroxidase activity and a Behavioural model (adjusted R = 79.8%) comprising Internal Locomotion and Time spent in open arms indices. In addition, a Combined model (adjusted R = 92.4%) and an Immunity-Redox model (adjusted R = 88.7%) were also constructed by combining the above-mentioned selected variables. The models were also cross-validated using two different sets of female mice (N = 30; N = 40). Correlation between predicted and observed life span was 0.849 (P < 0.000) for the Immunity model, 0.691 (P < 0.000) for the Redox, 0.662 (P < 0.000) for the Behavioural and 0.840 (P < 0.000) for the Immunity-Redox model. Thus, these results provide a new perspective on the use of immune function, redox and behavioural markers as prognostic tools in ageing research.
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http://dx.doi.org/10.1016/j.mad.2019.111125DOI Listing
September 2019

Altered Redox State in Whole Blood Cells from Patients with Mild Cognitive Impairment and Alzheimer's Disease.

J Alzheimers Dis 2019 ;71(1):153-163

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.

Oxidative stress plays an essential and early role in the pathophysiology of Alzheimer's disease (AD). Alterations in the redox state in AD and in mild cognitive impairment (MCI) patients appear in the brain and at peripheral level. Given that it is easier to study the latter, most of the research has been focused on plasma. However, the analysis of redox parameters in whole blood cells (including erythrocytes and leukocytes) has not really been investigated. Moreover, the association of these parameters with Mini-Mental State Examination (MMSE) clinical scores, has scarcely been studied. Therefore, the aim of the present work was to analyze several redox markers in whole blood cells from male and female MCI and AD patients. Antioxidant (superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), and reductase (GR) activities, and reduced glutathione (GSH) concentration) together with oxidant parameters (oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS)) were investigated using MCI and AD (10 women and 10 men in each group) and their age-matched control groups (15 women and 15 men). The results show an altered redox state in whole blood cells from AD patients (higher CAT, GSSG/GSH, TBARS and lower GPx, GR, GSH). Some of these redox parameters are already affected in MCI patients (higher TBARS and lower GPx and GR activities) in both sexes and, consequently, they could be used as markers of prodromal AD. Since GR, GSH, GSSG, and GSSG/GSH were found to be associated with MMSE scores, they seem to be useful clinically to monitor cognitive decline in AD progression.
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http://dx.doi.org/10.3233/JAD-190198DOI Listing
October 2020

Function, Oxidative, and Inflammatory Stress Parameters in Immune Cells as Predictive Markers of Lifespan throughout Aging.

Oxid Med Cell Longev 2019 2;2019:4574276. Epub 2019 Jun 2.

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.

According to the oxidative-inflammatory theory of aging, there is a link between the function, the oxidative-inflammatory stress state of immune cells, and longevity. However, it is unknown which immune cell parameters can predict lifespan and if there would be any changes in this prediction, depending on the age of the subject. Therefore, a longitudinal study in mice was performed analysing immune function (chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer (NK) activity, and lymphoproliferation capacity), antioxidant (catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities as well as reduced glutathione (GSH) concentrations), oxidant (oxidized glutathione (GSSG), superoxide anion, and malondialdehyde (MDA) concentrations), and inflammation-related markers (basal release of IL-1, IL-6, TNF-, and IL-10) in peritoneal leukocytes from mice at the adult, mature, old, very old, and long-lived ages (40, 56, 72, 96, and 120 ± 4 weeks of age, respectively). The results reveal that some of the investigated parameters are determinants of longevity at the adult age (lymphoproliferative capacity, lymphocyte chemotaxis, macrophage chemotaxis and phagocytosis, GPx activity, and GSH, MDA, IL-6, TNF-, and IL-10 concentrations), and therefore, they could be proposed as markers of the rate of aging. However, other parameters are predictive of extreme longevity only at the very old age (NK activity, CAT and GR activities, and IL-6 and IL-1 concentrations), and as such, they could reflect some of the adaptive mechanisms underlying the achievement of high longevity. Nevertheless, although preliminary, the results of the present study provide a new perspective on the use of function, redox, and inflammatory parameters in immune cells as prognostic tools in aging research and represent a novel benchmark for future work aimed at prediction of lifespan.
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http://dx.doi.org/10.1155/2019/4574276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589234PMC
February 2020

Fitness Features Involved in the Biocontrol Interaction of With Host Plants: The Case Study of PcPCL1606.

Front Microbiol 2019 10;10:719. Epub 2019 Apr 10.

Departamento de Microbiología, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain.

The goal of this mini review is to summarize the relevant contribution of some beneficial traits to the behavior of the species , and using that information, to give a practical point of view using the model biocontrol strain PCL1606 (PcPCL1606). Among the group of plant-beneficial rhizobacteria, has emerged as a plant- and soil-related bacterium that is mainly known because of its biological control of phytopathogenic fungi. Many traits have been reported to be crucial during the multitrophic interaction involving the plant, the fungal pathogen and the soil environment. To explore the different biocontrol-related traits, the biocontrol rhizobacterium PcPCL1606 has been used as a model in recent studies. This bacterium is antagonistic to many phytopathogenic fungi and displays effective biocontrol against fungal phytopathogens. Antagonistic and biocontrol activities are directly related to the production of the compound 2-hexyl, 5-propyl resorcinol (HPR), despite the production of other antifungal compounds. Furthermore, PcPCL1606 has displayed additional traits regarding its fitness in soil and plant root environments such as soil survival, efficient plant root colonization, cell-to-cell interaction or promotion of plant growth.
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http://dx.doi.org/10.3389/fmicb.2019.00719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469467PMC
April 2019

Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson's Disease Patients.

Int J Mol Sci 2019 Feb 12;20(3). Epub 2019 Feb 12.

Department of Genetics, Physiology and Microbiology, Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain.

In Parkinson's Disease (PD), the peripheral changes in the functional capacity and redox state of immune cells has been scarcely investigated, especially in the early PD stages. Aging is a risk factor for PD, and the age-related impairment of the immune system, based on a chronic-oxidative stress situation, is involved in the rate of aging. We analyzed several functions in isolated peripheral blood neutrophils and mononuclear cells from PD stage 2 patients, and compared the results to those in healthy elderly and adult controls. Several oxidative stress and damage parameters were studied in whole blood cells. The results showed an impairment of the lymphoproliferative response in stimulated conditions in the PD patients compared with age-matched controls, who also showed typical immunosenescence in comparison with adult individuals. Higher oxidative stress and damage were observed in whole blood cells from PD patients (lower glutathione peroxidase activity, and higher oxidized glutathione and malondialdehyde contents). Our results suggest an accelerated immunosenescence in PD stage 2, and that several of the parameters studied could be appropriate peripheral biomarkers in the early stages of PD.
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http://dx.doi.org/10.3390/ijms20030771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386872PMC
February 2019

Redox Parameters as Markers of the Rate of Aging and Predictors of Life Span.

J Gerontol A Biol Sci Med Sci 2020 03;75(4):613-620

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.

Oxidative stress has been reported to increase with aging, and although several age-related changes in redox parameters have been described, none of them have been verified as markers of the rate of aging and life span. Therefore, antioxidant (catalase, glutathione peroxidase, reductase activities, and reduced glutathione) and oxidant (oxidized glutathione, basal superoxide anion, and malondialdehyde concentrations) parameters were studied in whole blood cells from humans divided into different age groups (adult, mature, older adult, nonagenarian, and centenarian) in a cross-sectional study. Moreover, the same parameters were investigated in peritoneal leukocytes of mice at the analogous human ages (adult, mature, old, very old, and long-lived) in a longitudinal study as well as in adult prematurely aging mice. The results reveal that the age-related alterations of these markers are similar in humans and mice, with decreased antioxidants and increased oxidants in old participants, whereas long-lived individuals show similar values to those in adults. In addition, adult prematurely aging mice showed similar values to those in chronologically old mice and had a shorter life span than nonprematurely aging mice. Thus, these parameters could be proposed as markers of the rate of aging and used to ascertain biological age in humans.
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http://dx.doi.org/10.1093/gerona/glz033DOI Listing
March 2020

Protein Carbamylation: A Marker Reflecting Increased Age-Related Cell Oxidation.

Int J Mol Sci 2018 May 17;19(5). Epub 2018 May 17.

Biology Systems Department, Physiology, Alcala University, Alcala de Henares, 28805 Madrid, Spain.

Carbamylation is a post-translational modification of proteins that may partake in the oxidative stress-associated cell damage, and its increment has been recently proposed as a "hallmark of aging". The molecular mechanisms associated with aging are related to an increased release of free radicals. We have studied whether carbamylated proteins from the peripheral blood of healthy subjects are related to oxidative damage and aging, taking into account the gender and the immune profile of the subjects. The study was performed in healthy human volunteers. The detection of protein carbamylation and malondialdehyde (MDA) levels was evaluated using commercial kits. The immune profile was calculated using parameters of immune cell function. The results show that the individuals from the elderly group (60⁻79 years old) have increased carbamylated protein and MDA levels. When considered by gender, only men between 60 and 79 years old showed significantly increased carbamylated proteins and MDA levels. When those subjects were classified by their immune profile, the carbamylated protein levels were higher in those with an older immune profile. In conclusion, the carbamylation of proteins in peripheral blood is related to age-associated oxidative damage and to an aging functional immunological signature. Our results suggest that carbamylated proteins may play an important role at the cellular level in the aging process.
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http://dx.doi.org/10.3390/ijms19051495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983744PMC
May 2018

Frailty Quantified by the "Valencia Score" as a Potential Predictor of Lifespan in Mice.

J Gerontol A Biol Sci Med Sci 2018 09;73(10):1323-1329

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.

The development of frailty scores suitable for mice and which resemble those used in the clinical scenario is of great importance to understand human frailty. The aim of the study was to determine an individual frailty score for each mouse at different ages and analyze the association between the frailty score and its lifespan. For this purpose, the "Valencia Score" for frailty was used. Thus, a longitudinal study in mice was performed analyzing weight loss, running time and speed, grip strength and motor coordination at the late-adult, mature and old ages (40, 56 and 80 weeks old, respectively). These parameters are equivalent to unintentional weight loss, poor endurance, slowness, weakness, and low activity level, respectively, in humans. A cut-off point was used to identify frail mice for each criterion. All the measurements were also performed on chronologically adult prematurely aging mice. The results show that by using the "Valencia Score" for frailty a prematurely aged phenotype can be identified even during the adulthood of animals. This opens up the possibility of carrying out preventive long-term interventions. Moreover, the individual frailty score of a given mouse at the late-adult, mature and old ages is shown to be a relevant predictor of its lifespan.
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http://dx.doi.org/10.1093/gerona/gly064DOI Listing
September 2018

Impairment of Several Immune Functions and Redox State in Blood Cells of Alzheimer's Disease Patients. Relevant Role of Neutrophils in Oxidative Stress.

Front Immunol 2017 11;8:1974. Epub 2018 Jan 11.

Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.

Since aging is considered the most risk factor for sporadic Alzheimer's Disease (AD), the age-related impairment of the immune system (immunosenescence), based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD) and severe AD, and of age-matched controls (elderly healthy subjects) as well as of adult controls. The cognitive decline of all subjects was determined by Mini-Mental State Examination (MMSE) test (mAD stage was established at 20 ≤ MMSE ≤ 23 score; AD stage at <18 MMSE; elderly subjects >27 MMSE). The results showed an impairment of the immune functions of human peripheral blood neutrophils and mononuclear cells of mAD and AD patients in relation to healthy elderly subjects, who showed the typical immunosenescence in comparison with the adult individuals. However, several alterations were only observed in severe AD patients (lower chemotaxis, lipopolysaccharide lymphoproliferation, and interleukin (IL)-10 release; higher basal proliferation, tumor necrosis factor (TNF)-α release, and IL-10/TNF-α ratio), others only in mAD subjects (higher adherence), meanwhile others appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation and higher IL-6 release). This impairment of immune functions could be mediated by: (1) the higher oxidative stress and damage also observed in blood cells from mAD and AD patients and in isolated neutrophils [lower glutathione (GSH) levels, high oxidized glutathione (GSSG)/GSH ratio, and GSSG and malondialdehyde contents], and (2) the higher release of basal pro-inflammatory cytokines (IL-6 and TNF-α) found in AD patients. Because the immune system parameters studied are markers of health and rate of aging, our results supported an accelerated immunosenescence in AD patients. We suggest the assessment of oxidative stress and function parameters in peripheral blood cells as well as in isolated neutrophils and mononuclear cells, respectively, as possible markers of AD progression.
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http://dx.doi.org/10.3389/fimmu.2017.01974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768621PMC
January 2018

An Appropriate Modulation of Lymphoproliferative Response and Cytokine Release as Possible Contributors to Longevity.

Int J Mol Sci 2017 Jul 24;18(7). Epub 2017 Jul 24.

Department of Animal Physiology II, Faculty of Biology, Complutense University, Madrid 28040, Spain.

The decrease in the proliferative response of lymphocytes is one of the most evident among the age-related changes of the immune system. This has been linked to a higher risk of mortality in both humans and experimental animals. However, long-lived individuals, in spite of optimally maintaining most of the functions of the immune system, also seem to show an impaired proliferative response. Thus, it was hypothesized that these individuals may have distinct evolution times in this proliferation and a different modulatory capacity through their cytokine release profiles. An individualized longitudinal study was performed on female ICR-CD1 mice, starting at the adult age (40 weeks old), analyzing the proliferation of peritoneal leukocytes at different ages in both basal conditions and in the presence of the mitogen Concanavalin A, for 4, 24 and 48 h of culture. The cytokine secretions (IL-2, IL-17, IL-1β, IL-6, TNF-α and IL-10) in the same cultures were also studied. Long-lived mice show a high proliferative capacity after short incubation times and, despite experiencing a functional decline when they are old, are able to compensate this decrease with an appropriate modulation of the lymphoproliferative response and cytokine release. This could explain their elevated resistance to infections and high longevity.
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http://dx.doi.org/10.3390/ijms18071598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536085PMC
July 2017

Impact of motility and chemotaxis features of the rhizobacterium Pseudomonas chlororaphis PCL1606 on its biocontrol of avocado white root rot.

Int Microbiol 2017 Jun;20(2):95-104

Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora", IHSM-UMA-CSIC. Departamento de Microbiología, Facultad de Ciencias, Campus de Teatinos, 29071 Málaga, Spain.

The biocontrol rhizobacterium Pseudomonas chlororaphis PCL1606 has the ability to protect avocado plants against white root rot produced by the phytopathogenic fungus Rosellinia necatrix. Moreover, PCL1606 displayed direct interactions with avocado roots and the pathogenic fungus. Thus, nonmotile (flgK mutant) and non-chemotactic (cheA mutant) derivatives of PCL1606 were constructed to emphasize the importance of motility and chemotaxis in the biological behaviour of PCL1606 during the biocontrol interaction. Plate chemotaxis assay showed that PCL1606 was attracted to the single compounds tested, such as glucose, glutamate, succinate, aspartate and malate, but no chemotaxis was observed to avocado or R. necatrix exudates. Using the more sensitive capillary assay, it was reported that smaller concentrations (1 mM) of single compounds elicited high chemotactic responses, and strong attraction was confirmed to avocado and R. necatrix exudates. Finally, biocontrol experiments revealed that the cheA and fglK derivative mutants reduced root protection against R. necatrix, suggesting an important role for these biological traits in biocontrol by P. chlororaphis PCL1606. [Int Microbiol 20(2):94-104 (2017)].
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http://dx.doi.org/10.2436/20.1501.01.289DOI Listing
June 2017

Draft Genome Sequence of the Rhizobacterium PCL1601, Displaying Biocontrol against Soilborne Phytopathogens.

Genome Announc 2017 Apr 6;5(14). Epub 2017 Apr 6.

Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora" Universidad de Málaga, Consejo Superior de Investigaciones Científicas (IHSM-UMA-CSIC), Departamento de Microbiología, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain

In this study, we present the draft genome sequence of the bacterial strain PCL1601. This bacterium was isolated from the rhizosphere of healthy avocado trees and displayed antagonistic and biological control activities against different soilborne phytopathogenic fungi and oomycetes.
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http://dx.doi.org/10.1128/genomeA.00130-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383896PMC
April 2017

Characterization of biocontrol bacterial strains isolated from a suppressiveness-induced soil after amendment with composted almond shells.

Res Microbiol 2017 Jul - Aug;168(6):583-593. Epub 2017 Apr 1.

Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora"-Universidad de Málaga-Consejo Superior de Investigaciones Científicas (IHSM-UMA-CSIC), 29071 Málaga, Spain; Departamento de Microbiología, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, 29071 Málaga, Spain. Electronic address:

The improvement in soil quality of avocado crops through organic amendments with composted almond shells has a positive effect on crop yield and plant health, and enhances soil suppressiveness against the phytopathogenic fungus Rosellinia necatrix. In previous studies, induced soil suppressiveness against this pathogen was related to stimulation of Gammaproteobacteria, especially some members of Pseudomonas spp. with biocontrol-related activities. In this work, we isolated bacteria from this suppressiveness-induced amended soil using a selective medium for Pseudomonas-like microorganisms. We characterized the obtained bacterial collection to aid in identification, including metabolic profiles, antagonistic responses, hybridization to biosynthetic genes of antifungal compounds, production of lytic exoenzymatic activities and plant growth-promotion-related traits, and sequenced and compared amplified 16S rDNA genes from representative bacteria. The final selection of representative strains mainly belonged to the genus Pseudomonas, but also included the genera Serratia and Stenotrophomonas. Their biocontrol-related activities were assayed using the experimental avocado model, and results showed that all selected strains protected the avocado roots against R. necatrix. This work confirmed the biocontrol activity of these Gammaproteobacteria-related members against R. necatrix following specific stimulation in a suppressiveness-induced soil after a composted almond shell application.
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http://dx.doi.org/10.1016/j.resmic.2017.03.007DOI Listing
January 2018

Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice.

Redox Biol 2017 08 9;12:423-437. Epub 2017 Mar 9.

Department of Animal Physiology II, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Institute of Investigation Hospital 12 Octubre (i+12), Madrid, Spain. Electronic address:

The age-related changes in the immune functions (immunosenescence) may be mediated by an increase of oxidative stress and damage affecting leukocytes. Although the "oxidation-inflammation" theory of aging proposes that phagocytes are the main immune cells contributing to "oxi-inflamm-aging", this idea has not been corroborated. The aim of this work was to characterize the age-related changes in several parameters of oxidative stress and immune function, as well as in lipofuscin accumulation ("a hallmark of aging"), in both total peritoneal leukocyte population and isolated peritoneal macrophages. Adult, mature, old and long-lived mice (7, 13, 18 and 30 months of age, respectively) were used. The xanthine oxidase (XO) activity-expression, basal levels of superoxide anion and ROS, catalase activity, oxidized (GSSG) and reduced (GSH) glutathione content and lipofuscin levels, as well as both phagocytosis and digestion capacity were evaluated. The results showed an age-related increase of oxidative stress and lipofuscin accumulation in murine peritoneal leukocytes, but especially in macrophages. Macrophages from old mice showed lower antioxidant defenses (catalase activity and GSH levels), higher oxidizing compounds (XO activity/expression and superoxide, ROS and GSSG levels) and lipofuscin levels, together with an impaired macrophage functions, in comparison to adults. In contrast, long-lived mice showed in their peritoneal leukocytes, and especially in macrophages, a well-preserved redox state and maintenance of their immune functions, all which could account for their high longevity. Interestingly, macrophages showed higher XO activity and lipofuscin accumulation than lymphocytes in all the ages analyzed. Our results support that macrophages play a central role in the chronic oxidative stress associated with aging, and the fact that phagocytes are key cells contributing to immunosenescence and "oxi-inflamm-aging". Moreover, the determination of oxidative stress and immune function parameters, together with the lipofuscin quantification, in macrophages, can be used as useful markers of the rate of aging and longevity.
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http://dx.doi.org/10.1016/j.redox.2017.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357673PMC
August 2017

Immune function parameters as markers of biological age and predictors of longevity.

Aging (Albany NY) 2016 11;8(11):3110-3119

Department of Animal Physiology II, Faculty of Biology, Complutense University, Madrid, Spain.

Chronological age is not a good indicator of how each individual ages and thus how to maintain good health. Due to the long lifespan in humans and the consequent difficulty of carrying out longitudinal studies, finding valid biomarkers of the biological age has been a challenge both for research and clinical studies. The aim was to identify and validate several immune cell function parameters as markers of biological age. Adult, mature, elderly and long-lived human volunteers were used. The chemotaxis, phagocytosis, natural killer activity and lymphoproliferation in neutrophils and lymphocytes of peripheral blood were analyzed. The same functions were measured in peritoneal immune cells from mice, at the corresponding ages (adult, mature, old and long lived) in a longitudinal study. The results showed that the evolution of these functions was similar in humans and mice, with a decrease in old subjects. However, the long-lived individuals maintained values similar to those in adults. In addition, the values of these functions in adult prematurely aging mice were similar to those in chronologically old animals, and they died before their non-prematurely aging mice counterparts. Thus, the parameters studied are good markers of the rate of aging, allowing the determination of biological age.
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http://dx.doi.org/10.18632/aging.101116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191888PMC
November 2016

Hsp70 basal levels, a tissue marker of the rate of aging and longevity in mice.

Exp Gerontol 2016 11 28;84:21-28. Epub 2016 Aug 28.

Department of Animal Physiology II, Faculty of Biology, Complutense University, Madrid, Spain; Institute of Investigation, Hospital 12 Octubre, Madrid. Electronic address:

Under stressful conditions, the expression of the chaperone Hsp70 is induced, which acts as a cellular defense mechanism. The impairment in this induction has been related to aging, whereas an increased expression has been related to longevity. Nevertheless, it is still not known if the basal levels of Hsp70 can be indicative of the aging rate of different tissues. The aim of this study was to quantify the basal levels of Hsp70 in tissues from female mice throughout their aging process including long-lived mice, as well as from prematurely aging mice (PAM). Adult, old and long-lived (6, 18 and 30months of age, respectively) female ICR-CD1 and Balb/C mice were used. Tissues with mainly mitotic (liver and renal medulla) or post-mitotic (heart, renal cortex, cerebral cortex, spleen) cells and peritoneal leukocytes from these animals as well as from adult PAM and non-prematurely aging mice (NPAM), were studied. Basal levels of Hsp70 were assessed using an ELISA method. The results showed that the aging-associated variation of the levels of Hsp70 followed a different pattern in post-mitotic and mitotic tissues, being lower or higher in old mice comparing to adults, respectively. In all the tissues analyzed the Hsp70 levels from long-lived mice were similar to those from adult animals. In addition, in adult PAM these Hsp70 levels were similar to those in chronologically old animals. In conclusion, Hsp70 basal levels show tissue-specific age-associated variations and are preserved in long-lived animals, demonstrating their role as markers of the rate of aging and longevity.
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http://dx.doi.org/10.1016/j.exger.2016.08.013DOI Listing
November 2016

Microbial Profiling of a Suppressiveness-Induced Agricultural Soil Amended with Composted Almond Shells.

Front Microbiol 2016 22;7. Epub 2016 Jan 22.

Departamento de Microbiología, Facultad de Ciencias, Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora", Universidad de Málaga, Consejo Superior de Investigaciones Científicas Málaga, Spain.

This study focused on the microbial profile present in an agricultural soil that becomes suppressive after the application of composted almond shells (AS) as organic amendments. For this purpose, we analyzed the functions and composition of the complex communities present in an experimental orchard of 40-year-old avocado trees, many of them historically amended with composted almond shells. The role of microbes in the suppression of Rosellinia necatrix, the causative agent of avocado white root rot, was determined after heat-treatment and complementation experiments with different types of soil. Bacterial and fungal profiles obtained from natural soil samples based on the 16S rRNA gene and ITS sequencing revealed slight differences among the amended (AS) and unamended (CT) soils. When the soil was under the influence of composted almond shells as organic amendments, an increase in Proteobacteria and Ascomycota groups was observed, as well as a reduction in Acidobacteria and Mortierellales. Complementary to these findings, functional analysis by GeoChip 4.6 confirmed these subtle differences, mainly present in the relative abundance of genes involved in the carbon cycle. Interestingly, a group of specific probes included in the "soil benefit" category was present only in AS-amended soils, corresponding to specific microorganisms previously described as potential biocontrol agents, such as Pseudomonas spp., Burkholderia spp., or Actinobacteria. Considering the results of both analyses, we determined that AS-amendments to the soil led to an increase in some orders of Gammaproteobacteria, Betaproteobacteria, and Dothideomycetes, as well as a reduction in the abundance of Xylariales fungi (where R. necatrix is allocated). The combination of microbial action and substrate properties of suppressiveness are discussed.
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http://dx.doi.org/10.3389/fmicb.2016.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722121PMC
February 2016

Organic amendments to avocado crops induce suppressiveness and influence the composition and activity of soil microbial communities.

Appl Environ Microbiol 2015 May 13;81(10):3405-18. Epub 2015 Mar 13.

Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora," Universidad de Málaga, Consejo Superior de Investigaciones Científicas, and Departamento de Microbiología, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain

One of the main avocado diseases in southern Spain is white root rot caused by the fungus Rosellinia necatrix Prill. The use of organic soil amendments to enhance the suppressiveness of natural soil is an inviting approach that has successfully controlled other soilborne pathogens. This study tested the suppressive capacity of different organic amendments against R. necatrix and analyzed their effects on soil microbial communities and enzymatic activities. Two-year-old avocado trees were grown in soil treated with composted organic amendments and then used for inoculation assays. All of the organic treatments reduced disease development in comparison to unamended control soil, especially yard waste (YW) and almond shells (AS). The YW had a strong effect on microbial communities in bulk soil and produced larger population levels and diversity, higher hydrolytic activity and strong changes in the bacterial community composition of bulk soil, suggesting a mechanism of general suppression. Amendment with AS induced more subtle changes in bacterial community composition and specific enzymatic activities, with the strongest effects observed in the rhizosphere. Even if the effect was not strong, the changes caused by AS in bulk soil microbiota were related to the direct inhibition of R. necatrix by this amendment, most likely being connected to specific populations able to recolonize conducive soil after pasteurization. All of the organic amendments assayed in this study were able to suppress white root rot, although their suppressiveness appears to be mediated differentially.
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http://dx.doi.org/10.1128/AEM.03787-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407234PMC
May 2015

Increase of oxidation and inflammation in nervous and immune systems with aging and anxiety.

Curr Pharm Des 2014 ;20(29):4656-78

Department of Physiology (Animal Physiology II), Faculty of Biological Sciences, Madrid Complutense University, José Antonio Novais, 2, 28040 Madrid, Spain.

According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the agerelated impairment of organism functions, including those of the nervous and immune systems, as well as of the neuroimmune communication, which explains the altered homeostasis and the resulting increase of morbidity and mortality. Overproduction of oxidant compounds can induce an inflammatory response, since oxidants are inflammation effectors. Thus, oxidation and inflammation are interlinked processes and have many feedback loops. However, the nature of their potential interactions, mainly in the brain and immune cells, and their key involvement in aging remain unclear. Moreover, in the context of the neuroimmune communication, it has been described that an oxidative-inflammatory situation occurs in subjects with anxiety, and this situation contributes to an immunosenescence, alteration of survival responses and shorter life span. As an example of this, a model of premature aging in mice, in which animals show a poor response to stress and high levels of anxiety, an oxidative stress in their immune cells and tissues, as well as a premature immunosenescence and a shorter life expectancy, will be commented in the present review. This model supports the hypothesis that anxiety can be a situation of chronic oxidative stress and inflammation, especially in brain and immune cells, and this accelerates the rate of aging.
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http://dx.doi.org/10.2174/1381612820666140130201734DOI Listing
April 2015

[Premature immunosenescence in triple-transgenic mice for Alzheimer's disease].

Rev Esp Geriatr Gerontol 2014 Jan-Feb;49(1):15-9. Epub 2013 Dec 7.

Departamento de Fisiología, Facultad de Biología, Universidad Complutense de Madrid, Madrid, España. Electronic address:

Introduction: A deterioration of the neuroimmunoendocrine network has been observed in Alzheimer's disease (AD). However, the peripheral immune response has hardly been investigated in this pathology. Since some immune function parameters have been established as good markers of the rate of ageing, and can predict longevity, the aim of the present work was to study some of these functions in splenic leucocytes in transgenic mice for AD of different ages.

Material And Methods: Young female (4 ± 1 months), adult (9 ± 1 months), and mature (12 ± 1 months) triple-transgenic mice for AD (3 xTgAD) and non-transgenic (NTg) control mice of the same ages were used. The chemotaxis, the anti-tumour activity of « natural killer » (NK) cells and the lymphoproliferative response in the presence of the mitogens concanavalin A and lipopolysaccharide, functions that decrease with age, were determined in splenic leucocytes. In addition, the differences in lifespan between 3 xTgAD and NTg were studied in parallel using other animals, until their death through natural causes.

Results: In 3 xTgAD, with respect to NTg, chemotaxis decreased at all ages studied, whereas in lymphoproliferative response this reduction was shown at 4 months and 9 months. NK activity was diminished only in young 3 xTgAD with respect to NTg. The 3 xTgAD showed a shorter lifespan than the NTg control group.

Conclusions: The 3 xTgAD mice show a premature immunosenescence, which could explain their early mortality. The determination of these immune functions at peripheral level could serve as a marker of the progression of the Alzheimer's disease.
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http://dx.doi.org/10.1016/j.regg.2013.04.003DOI Listing
April 2015

Peripheral immune system and neuroimmune communication impairment in a mouse model of Alzheimer's disease.

Ann N Y Acad Sci 2012 Jul;1262:74-84

Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.

Neurodegenerative diseases such as Alzheimer's disease (AD) can be understood in the context of the aging of neuroimmune communication. Although the contribution to AD of the immune cells present in the brain is accepted, the role of the peripheral immune system is less well known. The present review examines the behavior and the function and redox state of peripheral immune cells in a triple-transgenic mouse model (3×Tg-AD). These animals develop both beta-amyloid plaques and neurofibrillary tangles with a temporal- and regional-specific profile that closely mimics their development in the human AD brain. We have observed age and sex-related changes in several aspects of behavior and immune cell functions, which demonstrate premature aging. Lifestyle strategies such as physical exercise and environmental enrichment can improve these aspects. We propose that the analysis of the function and redox state of peripheral immune cells can be a useful tool for measuring the progression of AD.
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http://dx.doi.org/10.1111/j.1749-6632.2012.06639.xDOI Listing
July 2012

The aged-related increase in xanthine oxidase expression and activity in several tissues from mice is not shown in long-lived animals.

Biogerontology 2011 Dec 9;12(6):551-64. Epub 2011 Aug 9.

Department of Physiology (Animal Physiology II), Madrid Complutense University, José Antonio Novais, Spain.

Xanthine oxidase (XO) is an important source of oxidant production and plays an essential role in several oxidative stress-related diseases. Aging is associated with a progressive deregulation of homeostasis as a result of a chronic oxidative stress situation. In the present work the age-related changes in XO expression and activity, as well as the activities of superoxide dismutase and catalase have been investigated in liver, kidney and thymus from four different age groups of mice, including long-lived animals. Furthermore, we have evaluated the contribution of the XO to the oxidative stress-associated with aging, in comparison to another enzymatic key source of oxidant generation, the NADPH oxidase, in peritoneal leukocytes from old mice. In all the tissues analyzed, the old mice showed higher activity and expression of XO, and decreased or unchanged superoxide dismutase and catalase activities as compared with adult mice. Moreover, the inhibition of reactive oxygen species with allopurinol or apocynin in peritoneal leukocytes from old mice, suggest that both XO and NADPH oxidase contribute to the generation of superoxide anion, whereas the XO may have a special relevance in the production of hydrogen peroxyde. Finally, long-lived animals showed a well-preserved redox state, in terms of antioxidant defenses and oxidant compounds in tissues and immune cells, which may be related to the ability of these subjects to reach a very advanced age in healthy condition. These results confirm that XO plays an important role in the age-related oxidative stress in tissues and immune cells.
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http://dx.doi.org/10.1007/s10522-011-9351-6DOI Listing
December 2011