Cambios conductuales e inmunitarios en el envejecimiento cronológico, prematuro y acelerado. Estrategias para una longevidad saludable

El envejecimiento es un proceso universal, intrínseco, progresivo y deletéreo que podría definirse como el conjunto de cambios que afectan a todas nuestras células y tejidos al avanzar la edad, llevando a una pérdida progresiva de nuestras capacidades fisiológicas así como a una incapacidad para mantener la homeocinesis. Así mismo, el envejecimiento también se caracteriza por su heterogeneidad, de manera que no todos los cambios que suceden en los sistemas de un organismo se producen a la misma velocidad, así como tampoco lo hacen los individuos con una misma edad cronológica, lo que hace surgir el concepto de “edad biológica”, considerado un mejor indicador de la velocidad a la que envejece un individuo que la edad cronológica y siendo, por tanto, determinante de su esperanza de vida. Según la teoría de la oxidación-inflamación, este deterioro asociado con la edad sería consecuencia de un estrés oxidativo crónico asociado a un estrés inflamatorio, los cuales afectarían a todas las células, pero de manera más relevante a las de los sistemas reguladores, el nervioso, el endocrino y el inmunitario. La afectación de estos sistemas y, consecuentemente, de la comunicación entre ellos (comunicación psiconeuroinmunoendocrina) deteriora la homeocinesis y aumenta la morbilidad y mortalidad. Además, en esta teoría se propone que dadas las características del sistema inmunitario, el cual necesita producir oxidantes y compuestos inflamatorios en su función defensiva frente a patógenos y cánceres, si dicha producción no está bien regulada, puede entrar en un círculo vicioso que aumente el estrés oxidativo e inflamatorio del organismo. De esta forma, se sugiere que el sistema inmunitario no sólo puede modular la velocidad de envejecimiento de cada individuo sino que su capacidad funcional supone un excelente marcador del estado de salud. Los cambios que afectan al sistema inmunitario al envejecer se recogen bajo el término de inmunosenescencia y abarcan todos los niveles de organización de dicho sistema, desde genético hasta funcional..

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

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

Calidad de vida en pacientes con tuberculosis pulmonar del centro de salud Flor De Amancaes, Rimac 2022

Objetivo: Determinar calidad de vida relacionada a la salud en pacientes con tuberculosis del Centro de Salud Flor de Amancaes. Materiales y métodos: El enfoque fue cuantitativo, diseño no experimental, transversal y descriptivo. La población estuvo conformada por los 70 pacientes con tuberculosis pulmonar del C.S Flor de Amancaes ubicado en el distrito del Rímac. La muestra fue igual a la población. El cuestionario (CVRS) denominado SF-36, se encuentra estructurado por 36 preguntas y 9 dimensiones. Resultados: Respecto a la calidad de vida, 32 (45,7%) tuvieron una CV promedio. Respecto a la dimensión función física, 23 (32,9%) tuvieron una CV promedio. Respecto a la función rol físico, 22 (31,4%) tuvieron una CV baja. Respecto a la dimensión dolor corporal, 31 (44,3%) tuvieron una calidad de vida promedio. Respecto a la dimensión salud general, 22 (31,4%) tuvieron una calidad de vida promedio. Respecto a la dimensión vitalidad, 32 (45,7%) tuvieron una CV promedio. Respecto a la dimensión función social, 23 (32,9%) tuvieron una calidad de vida baja. Respecto a la dimensión rol emocional, 27 (38,6%) tuvieron una calidad de vida alta. Respecto a la salud mental, 36 (51,4%) tuvieron una CV promedio, 21 (30%) tuvieron una CV alta. Respecto a la transición de salud, 26 (37,1%) tuvieron una CV alta. Conclusiones: La calidad de vida relacionada a la salud en pacientes con tuberculosis del Centro de Salud Flor de Amancaes, tuvieron en su mayoría una calidad de vida promedio

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

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

Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behaviour, without changing mice longevity.

The membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the b1-blocker atenolol increased the amount of the extracellular-signal-regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer-lived mammals. This was mainly due to decreases in 22:6n-3 and increases in 18:1n-9 fatty acids. The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging-related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity. The controls reached 3.93 years of age, a substantially higher maximum longevity than the best previously described for this strain (3.0 years). Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. Weconclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug.This investigation was supported by I + D grants from the Spanish Ministry of Science and Innovation (BFU2011-23888 to G.Barja); UCMGroups of Research (910379ENEROINN), BFU2011-30336, and RETICEF (RD 12/0043/0018) from ISCIII-FEDER of the European Union to M. De la Fuente; Spanish Ministry of Health (PI11/01532) to M.Portero Otin; and Spanish Ministry of Science and Innovation (BFU2009-11879) and the Generalitat of Catalonia (2009SGR735) to R. Pamplona

Topographical and mechanical characterization of living eukaryotic cells on opaque substrates: development of a general procedure and its application to the study of non-adherent lymphocytes

The mechanical behavior of living murine T-lymphocytes was assessed by atomic force microscopy (AFM). A robust experimental procedure was developed to overcome some features of lymphocytes, in particular their spherical shape and non-adherent character. The procedure included the immobilization of the lymphocytes on amine-functionalized substrates, the use of hydrodynamic effects on the deflection of the AFM cantilever to monitor the approaching, and the use of the jumping mode for obtaining the images. Indentation curves were analyzed according to Hertz's model for contact mechanics. The calculated values of the elastic modulus are consistent both when considering the results obtained from a single lymphocyte and when comparing the curves recorded from cells of different specimen

Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines

Objective. The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. Methods. Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. Results. A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). Conclusion. In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.Fil: Isnardi, Carolina A.. No especifíca;Fil: Cerda, Osvaldo L.. No especifíca;Fil: Landi, Margarita. Austral University Hospital; LiberiaFil: Cruces, Leonel Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Schneeberger, Emilce E.. No especifíca;Fil: Montoro, Claudia Calle. Austral University Hospital; LiberiaFil: Alfaro, María Agustina. No especifíca;Fil: Roldán, Brian M.. No especifíca;Fil: Gómez Vara, Andrea B.. No especifíca;Fil: Giorgis, Pamela. No especifíca;Fil: Ezquer, Roberto Alejandro. No especifíca;Fil: Crespo Rocha, María G. No especifíca;Fil: Reyes Gómez, Camila R.. No especifíca;Fil: de Los Ángeles Correa, Mária. No especifíca;Fil: Rosemffet, Marcos G.. No especifíca;Fil: Abarza, Virginia Carrizo. No especifíca;Fil: Pellet, Santiago Catalan. Austral University Hospital; LiberiaFil: Perandones, Miguel. No especifíca;Fil: Reimundes, Cecilia. Austral University Hospital; LiberiaFil: Longueira, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Quintana, Rosana Maris. No especifíca;Fil: de la Vega, María Celina. No especifíca;Fil: Kreplak, Nicolás. No especifíca;Fil: Pifano, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maid, Pablo. Austral University Hospital; LiberiaFil: Pons Estel, Guillermo J.. No especifíca;Fil: Citera, Gustavo. No especifíca

Respuesta immune humoral asociada a las vacunas contra SARS-CoV-2 en pacientes con artritis reumatoidea: datos del registro SAR-CoVAC

Introducción: la artritis reumatoidea (AR) y los tratamientos indicados para su manejo pueden afectar la respuesta a la vacuna para SARS-CoV-2. Sin embargo, aún no se cuenta con datos locales. Objetivos: evaluar la respuesta humoral de la vacuna para SARS-CoV-2 y su seguridad en esta población. Materiales y métodos: estudio observacional. Se incluyeron pacientes ≥18 años, con AR ACR/EULAR 2010 que recibieron la vacunación para SARS-CoV-2

Improvement of Redox state and functions of immune cells as well as of behavioral response in aged mice after two‑week supplementation of fermented milk with Probiotics

The homeostatic systems, such as the nervous and immune systems, show deterioration in aging as a consequence of the agerelated oxidative-infammatory stress establishment. The supplementation with fermented milk containing probiotic bacteria could be a good nutritional strategy to improve homeostatic system functions in aged individuals through the modulation of their redox state. The aim of the present study was to evaluate the efect of 2-week supplementation with a commercial fermented milk containing yogurt species (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus), and the probiotic Lactobacillus casei DN-114001 on behavior, redox state, and immune cell functions of aged mice as well as on their life span. Aged female ICR-CD1 mice were supplemented with fermented milk containing these probiotics for 2 weeks. After this period, a variety of behavioral tests were performed and several parameters of redox state and function of peritoneal leukocytes were analyzed. The results showed that the 2-week supplementation of fermented milk containing probiotics improved behavior (such as muscular vigor, exploratory activity, and anxiety-like behavior) as well as the redox state and functions of peritoneal immune cells in aged mice. In conclusion, the present study shows that the supplementation with fermented milk containing probiotics for a short period of time could be a good nutritional strategy to promote healthy aging.Institute de Salud Carlos III – Fondo Europeo de Desarrollo Regional (ISCIII-FEDER)Universidad complutense de MadridDepto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu

Desgaste de dientes incisivos en caballos con aerofagia. Estudio preliminar

The objective of this study was to quantify the wear of the upper central incisors in stabled and crib-biting Thoroughbred race horses. The sixteen horses located at the Club Hípico Concepción were divided into 2 groups: control (non crib-biting) (n=7) and crib-biting affected (n=9) one. All horses had no access to pasture. A shallow horizontal incision of 5 mm long was made in the labial face of 101 and 201 dental pieces, using a triangular file, at 10 mm from the occlusal edge. The distance from the occlusal edge to the incision was measured again after six months, to determine wear. Results are expressed as the average and standard deviations from wearing measurements. To compare the wear between the two groups, the Student’s t-test was carried out with a pEl objetivo del estudio fue cuantificar el desgaste de los incisivos centrales superiores en caballos Fina Sangre de Carrera estabulados y con aerofagia. Se evaluaron 16 caballos fina sangre de carrera residentes en el Club Hípico Concepción, divididos en 2 grupos: control (sin aerofagia) (n=7) y con aerofagia (n=9). Todos estabulados y sin acceso a pastoreo. A cada caballo, en la cara labial de las piezas dentales 101 y 201 se midió 10 mm desde la superficie oclusal y con una lima triangular se realizó una marca superficial horizontal de 5 mm de largo. Para determinar el desgaste dental, a los 6 meses se midió la distancia desde la superficie oclusal a la marca horizontal. Los resultados se expresan como promedio y desviación estándar. Para comparar el desgaste dental entre ambos grupos se utilizó la prueba t de Student, con un nivel de significancia de