Academic literature on the topic 'Grado de senescencia'

Low-grade chronic inflammation is a common denominator in atherogenesis and related diseases. Solid evidence supports the occurrence of an impairment in the innate and adaptive immune system with senescence, favoring the development of acute and chronic age-related diseases. Cardiovascular (CV) diseases (CVD), in particular, are a leading cause of death even at older ages. Inflammation-associated mechanisms that contribute to CVD development include dysregulated redox and metabolic pathways, genetic modifications, and infections/dysbiosis. In this review, we will recapitulate the determinants and consequences of the immune system dysfunction at older age, with particular focus on the CV system. We will examine the currently available and potential future strategies to counteract accelerated CV aging, i.e., nutraceuticals, probiotics, caloric restriction, physical activity, smoking and alcohol cessation, control of low-grade inflammation sources, senolytic and senescence-modulating drugs, and DNA-targeting drugs.

Aging and age-related diseases (ARDs) share basic mechanisms largely involving inflammation. A chronic, low-grade, subclinical inflammation called inflammaging occurs during aging. Autophagy defects, oxidative stresses, senescence-associated secretory phenotypes (SASPs), and DNA damage generally contribute to inflammaging and are largely regulated by numerous lncRNA through two-level vicious cycles disrupting cellular homeostasis: (1) inflammaging and the cellular senescence cascade and (2) autophagy defects, oxidative stress, and the SASP cascade. SASPs and inflammasomes simultaneously cause inflammaging. This review discusses the involvement of macrophage inflammaging in various ARDs and its regulation via lncRNA. Among macrophages, this phenomenon potentially impairs its immunosurveillance and phagocytosis mechanisms, leading to decreased recognition and clearance of malignant and senescent cells. Moreover, SASPs extracellularly manifest to induce paracrine senescence. Macrophage senescence escalates to organ level malfunction, and the organism is more prone to ARDs. By targeting genes and proteins or functioning as competing endogenous RNA (ceRNA), lncRNA regulates different phenomena including inflammaging and ARDs. The detailed mechanism warrants further elucidation to obtain pathological evidence of ARDs and potential treatment approaches.

77 Background: Prostate cancer is a leading cause of cancer related death in men worldwide, with recurrence being a major clinical problem after radiotherapy. There is an unmet need to better characterize radioresistant tumors and identify biomarkers to improve patient outcomes. Methods: We identified that miR-106a was overexpressed in radiation resistant cell lines compared to parental cells. We analyzed The Cancer Genome Atlas dataset to assess miR-106a expression in normal prostate, and low- to high-grade prostate tumors. To assess the functional role of miR-106a, we performed in vitro and in vivo assays for radiation response, including clonogenic survival, proliferation, senescence, and tumor xenograft growth after radiation. We performed gene array and pathway analyses to identify downstream effectors of miR-106a. Results: MiR-106a expression was significantly higher in prostate tumors with Gleason score > 7 compared to Gleason ≤ 7, suggesting miR-106a is involved in high grade disease. MiR-106a overexpression confers radioresistance in vitro and in vivo, by targeting LITAF. We now extend miR-106a’s effects to upregulation of ATM at the promoter level, thereby increasing ATM transcript and protein in the cell. Unexpectedly, we found that miR-106a’s mechanism of radioresistance through ATM upregulation does not alter DNA damage repair. ATM upregulation affects clonogenic survival through reduced senescence. KU-55933, a specific ATM kinase inhibitor, resensitizes miR-106a overexpressing cells to radiation by inducing senescence, a predominant mode of cell death in prostate cancer. Conclusions: Our research challenges the current paradigm of ATM and DNA damage repair by outlining another mechanism of radioresistance through alteration of senescence. Our findings suggest that miR-106a may be a promising biomarker for high-grade disease and radioresistant prostate cancer. In addition, we have identified a therapeutic intervention for miR-106a induced radioresistance. Improvements in bioavailability of KU-55933 may lead to its clinical use in combination with radiation therapy to radiosensitize miR-106a induced radioresistant prostate cancer.

Many features of aging result from the incapacity of cells to adapt to stress conditions. When cells are overwhelmed by stress, they can undergo senescence to avoid unrestricted growth of damaged cells. Recent findings have proven that cellular senescence is more than that. A specific grade of senescence promotes embryo development, tissue remodeling and wound healing. However, constant stresses and a weakening immune system can lead to senescence chronicity with aging. The accumulation of senescent cells is directly related to tissue dysfunction and age-related pathologies. Centenarians, the most aged individuals, should accumulate senescent cells and suffer from their deleterious effects, however, they enjoy a compression of morbidity. We have shown that they overexpress B-cell lymphoma-extra large (Bcl-xL). Bcl-xL could avoid an excessive burden of senescent cells through the regulation of intrinsic apoptosis, mitochondrial bioenergetics and oxidative stress. On the other hand, Bcl-xL maintains a fully functional immune system that ensures an efficient clearance of senescent cells. Moreover, there is a paradox, as inhibitors of Bcl-xL have been employed as senolytic agents, which have been shown to protect from aging in animal models. In this review, we aim to discuss how Bcl-xL could modulate senescence-associated harmful effects in centenarians, protecting them from the burden of accumulation of senescent cells.

Aging is a major risk factor in the development of chronic diseases affecting various tissues including the cardiovascular system, muscle and bones. Age-related diseases are a consequence of the accumulation of cellular damage and reduced activity of protective stress response pathways leading to low-grade systemic inflammation and oxidative stress. Both inflammation and oxidative stress are major contributors to cellular senescence, a process in which cells stop proliferating and become dysfunctional by secreting inflammatory molecules, reactive oxygen species (ROS) and extracellular matrix components that cause inflammation and senescence in the surrounding tissue. This process is known as the senescence associated secretory phenotype (SASP). Thus, accumulation of senescent cells over time promotes the development of age-related diseases, in part through the SASP. Polyphenols, rich in fruits and vegetables, possess antioxidant and anti-inflammatory activities associated with protective effects against major chronic diseases, such as cardiovascular disease (CVD). In this review, we discuss molecular mechanisms by which polyphenols improve anti-oxidant capacity, mitochondrial function and autophagy, while reducing oxidative stress, inflammation and cellular senescence in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). We also discuss the therapeutic potential of polyphenols in reducing the effects of the SASP and the incidence of CVD.

412 Background: Immune cell infiltrates play a key role in determining colorectal cancer outcome. It is unclear whether they are tumour or host specific. Increased immunogenicity may relate to senescence or proliferation. Senescence, a state of cell-cycle arrest, slows tumour progression. In animal models, senescence associated regression is mediated by upregulated antitumour immune responses. High proliferation may provoke immune responses. Relationships between senescence, proliferation and immune cell infiltrates have not previously been studied. We explore whether p16ink4a associated senescence relates to T cell infiltrates in colorectal tumours and whether p16ink4a expression, proliferation and T cell infiltrates confer similar survival relationships. Methods: Immunostaining of nuclear p16inka and Ki67 was performed using a tissue microarray. Nuclear p16inkaand Ki67 were scored as high or low expression. (T cell markers CD3/CD45RO/CD8/FOXP3) were scored high/low grade on corresponding full sections (margin/stroma/ cancer cell nest). Results: 230 Stage I-III cancers were studied. High nuclear p16ink4a was expressed in 63% and high proliferation (Ki67 >15% ) in 61%. P16ink4a expression related to reduced margin, stroma and cancer cell nest (CCN) CD45RO cells (P=0.054, P=0.062, P=0.025) and reduced margin CD8 cells (P=0.016). High Ki67 labeling related to increased margin, and CCN CD3 cells (P=0.017, P<0.001), increased margin and CCN CD45RO cells (P=0.023, P<0.001), increased margin, stroma and CCN FOXP3 cells (P<0.001, P=0.001, P<0.001) and increased margin and CCN CD8 cells (P=0.026, P=0.001). On multivariate analysis, TNM stage (P<0.001), low margin CD3 (P=0.014), low margin CD8 (P=0.037), low proliferation (Ki67) (P=0.013) and low senescence (P16ink4a) (P=0.002) conferred poorer cancer survival. Conclusions: p16ink4a expression, proliferation and immune cell infiltrates are independent prognostic factors in colorectal cancer. Proliferation relates to increasing T cell infiltrates but independently influences survival. P16ink4a associated senescence does not appear to mediate improved outcome by upregulating T cell responses. Relationships observed here suggest the opposite.

Abstract Senescence and abscission of mature peanut pods is controlled by the ethylene cascade. Reducing senescence and abscission could involve inhibiting the ethylene cascade and allow greater harvest flexibility in peanut. Application of 1-methylcyclopropene (1-MCP), the ethylene binding inhibitor, may reduce senescence and abscission of mature peanut pods. Research was conducted from 2005 through 2008 in North Carolina to determine the effects of 1-MCP on pod yield and percentages of sound mature kernels (%SMK), sound splits (%SS), total sound mature kernels (%TSMK), other kernels (%OK), extra large kernels (%ELK), fancy pods (%FP), and pod retention. Treatments of 1-MCP were applied at 26 g ai/ha plus a crop oil concentrate at 7, 10, or 14 d prior to digging peanut at the projected optimum digging date. Peanut was dug at the projected optimum digging date or at 7 or 20 d after projected optimum digging date. The cultivars NC-V 11 (2005 and 2007), Phillips (2006 and 2007), and Perry (2008) were evaluated in separate experiments. Pod yield, %SMK, %TSMK, %SS, %OK, %ELK, and %FP were not affected by 1-MCP regardless of application timing when NC-V 11 and Phillips were evaluated. Only %SMK and %TSMK were affected by 1-MCP when applied to the cultivar Perry. Digging date affected pod yield and market grade characteristics. When digging of Phillips and Perry was delayed by 7 or 20 d past the optimum digging date, %SMK and %TSMK increased. Pod retention, determined by comparing the number and mass of pods/plant following digging, was affected by digging date and location but not 1-MCP treatment. These data suggest that 1-MCP will have little activity on peanut pod yield, market grade characteristics, or pod retention.

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La creciente expansión de la población urbana ha implicado en una fuerte presión de esta sobre los distintos componentes del medioambiente, especialmente del medio biótico, restringiendo y desplazando a las formas de vida que lo componen. La vegetación presente dentro de las zonas urbanas es uno de los elementos biofísicos más importantes presentes en ellas, aportando no solo con detalles estéticos, sino que también con un sinnúmero de funciones y servicios ambientales que benefician tanto al medioambiente como a la población. El presente estudio tiene como objetivo evaluar el efecto del grado de senescencia de la vegetación urbana en la presencia de la especie Veniliornis lignarius (carpinterito), especie de pájaro carpintero catalogada como la más pequeña del país. En enero del presente año (2017), se realizó un muestreo de 203 puntos aleatorios en polígonos que contenían por lo menos un 25% de cobertura vegetal en comunas urbanas y adyacentes a la Cordillera de los Andes en la Región Metropolitana, aplicando el método de los cuartos y la técnica del Playback para una caracterización de la vegetación urbana y el registro de presencias o ausencias de carpinteritos respectivamente. Con los datos se creó un índice de senescencia para cada punto de muestreo, variable que fue sometida a un proceso de regresión logística binaria junto con las generadas por el método de los cuartos (densidad, volumen, área basal y altura), evaluando cual o cuales de estas fueron significativas en la predicción de la presencia de carpinteritos dentro del área de estudio. La única variable con un efecto significativo en la presencia de carpinteritos es el grado de senescencia de la vegetación urbana, en donde a mayor senescencia mayor es la probabilidad de presencia de la especie. La muestra representada por las ausencias de carpinteritos se concentra principalmente en arboles clasificados como “maduros”, mientras que la muestra de las presencias tiende a distribuir a los individuos en las clasificaciones “maduros”, “Senescente 1” y “Senescente 2”.
The increasing expansion of the urban population has implied a strong pressure of this on the different components of the environment, especially of the biotic resource, restricting and displacing the forms of life that take part of this. The vegetation present in urban areas is one of the most important biophysical elements present in them, contributing not only with aesthetic details, but also with a number of environmental functions and services that benefit, the environment and the population equally. The objective of this research is evaluate the effect of the different senescence levels of the urban vegetation, in the presence of the species Veniliornis lignarius (carpinterito), that is the smallest woodpecker species in the country. In January of 2017, was sampled 203 random points in polygons that contain at least 25% of vegetation cover in urban areas, nearby to the Andes Mountains in the Region Metropolitana, applying the quarter method and the Playback technique, for a characterization of the urban vegetation and the record of presences or absences of carpinteritos. With the data, a senescence index was created for each sampling point, this index was subjected to a binary logistic regression process, together with those generated by the quarter method (density, volume, basal area and height), to evaluate which of these were significant in the prediction of the presence of carpinteritos. The only variable with a significant effect on the presence of carpinteritos is the senescence levels of the urban vegetation, where the greater senescence is the probability of presence of the species. The sample represented by the absence of carpinteritos is mainly concentrated in trees classified as "Mature", while the presence sample tends to distribute to individuals in the "mature", "Senescent 1" and "Senescent 2" classifications.

El objetivo general de esta tesis fue estudiar si la demora en la senescencia foliar (carácter stay-green, SG) en híbridos de maíz confiere tolerancia del rendimiento al estrés abiótico. Se realizaron ensayos a campo utilizando híbridos contrastantes en la senescencia foliar. Se registró la evolución de la senescencia, la producción neta de fotoasimilados, el rendimiento y sus componentes. Bajo sequía en post-floración, los genotipos SG presentaron mayor producción de fotoasimilados y esto se relacionó con mayor conductancia estomática y con la retención de área foliar verde (AFV). Esta ventaja se tradujo en mayor rendimiento (a través de un mayor peso de grano, PG) en dos ensayos; en el tercer ensayo los genotipos SG presentaron menor partición a espiga por lo que el rendimiento no se diferenció del grupo de híbridos no stay-green (NSG). En condiciones de deficiencias de N, los genotipos SG presentaron mayor producción de fotoasimilados en post-floración mientras las temperaturas mínimas se mantuvieron por encima de 10°C, pero pérdidas netas de materia seca por debajo de este umbral que no se observaron en los genotipos NSG o con mayor nivel de fertilización. El carácter SG no se relacionó con el rendimiento o con el PG a bajo nivel de N (18 kg de N ha-1) pero sí al aumentar la dosis de fertilización (100 y 200 kg de N ha-1). En condiciones de estrés por alta densidad poblacional, se compararon dos genotipos. El genotipo SG presentó menor producción de asimilados, y menor inducción de la senescencia de las hojas basales por sombreo. El genotipo SG demoró la senescencia aún cuando la absorción de N en post-floración fue menor que en el genotipo NSG. El PG se relacionó con la concentración de N en granos, y ambos fueron menores en el genotipo SG, resultando en menor rendimiento. En un tercer ensayo, se incorporaron dos genotipos adicionales. En uno de ellos, el carácter SG se mantuvo sólo en las hojas superiores; éste genotipo SG presentó mayor PG y rendimiento en comparación con los otros tres. Finalmente, se analizó la degradación de proteínas foliares durante el llenado. La degradación de proteínas se relacionó positivamente con el PG en condiciones de deficiencias de N pero inversamente cuando las plantas se fertilizaron con 200 kg N ha-1. Uno de los genotipos SG mostró muy escasa degradación de proteínas mientras que en otro SG la degradación aumentó en respuesta a las deficiencias de N. En conclusión, la contribución del carácter SG a la estabilidad del rendimiento depende de la capacidad que presenten los genotipos SG para ajustar la expresión del carácter en función del ambiente (por ejemplo, induciendo la senescencia en respuesta al sombreo, o por deficiencias de N edáfico).

Le cancer de l’ovaire (COv) est le cancer gynécologique le plus létal chez la femme et les traitements existants, chirurgie et chimiothérapie, ont peu évolué au cours des dernières décennies. Nous proposons que la compréhension des différents destins cellulaires tels que la sénescence que peuvent choisir les cellules du cancer de l’ovaire en réponse à la chimiothérapie pourrait conduire à de nouvelles opportunités thérapeutiques. La sénescence cellulaire a été largement associée à l’activité de la protéine TP53, qui est mutée dans plus de 90% des cas de cancer de l’ovaire séreux de haut grade (COv-SHG), la forme la plus commune de la maladie. Dans nos travaux, à partir d’échantillons dérivés de patientes, nous montrons que les cultures primaires du cancer de l’ovaire séreux de haut grade exposées au stress ou à des drogues utilisées en chimiothérapie entrent en senescence grâce à l’activité d’un isoforme du gène CDKN2A (p16INK4A). Dans ces cellules, nous avons évalué les caractéristiques fondamentales de la sénescence cellulaire tels que les altérations morphologiques, l’activité béta galactosidase associée à la sénescence, les dommages à l’ADN, l’arrêt du cycle cellulaire et le phénotype sécrétoire associé à la sénescence. En utilisant des micromatrices tissulaires construites à partir d’échantillons humains de COv-SHG pré- et post-chimiothérapie, accompagnées de leurs données cliniques, nous avons quantifié des marqueurs de sénescence incluant une diminution de la prolifération cellulaire quelques semaines après chimiothérapie. De façon intéressante, l’expression de p16INK4A dans les échantillons de COv-SHG prétraitement corrèle avec une survie prolongée des patientes suite au traitement. Ceci suggère ainsi pour la première fois un impact biologique bénéfique pour la présence de cellules cancéreuses qui sont capable d’activer la sénescence, particulièrement pour le traitement du cancer de l’ovaire. Dans le but de complémenter les thérapies actuelles avec des approches de manipulation pharmacologique de la sénescence, nos résultats suggèrent qu’il serait important de déterminer l’impact positif ou négatif de la sénescence induite par la thérapie sur la progression de la maladie et la survie, pour chaque type de cancer de façon indépendante.
Human ovarian cancer (OvCa) is the deadliest gynecologic malignancy and existing surgical/chemotherapeutic treatment options have been relatively static for decades. We propose that understanding OvCa cell fate decisions taken in response to chemotherapy could guide new therapeutic opportunities. Damage-induced cellular senescence is often associated with TP53 activity, which is heavily mutated in high grade serous (HGS) OvCa (>90%), the most common form of this disease. Here, using patient derived tissues, we show that primary HGS-OvCa cultures predominantly trigger CDKN2A- associated (p16INK4A isoform) senescence following exposure to stress or chemotherapy. Key senescence hallmarks including altered morphology, senescence-associated-Betagalactosidase, DNA damage, cell cycle arrest and the senescence-associated secretory phenotype were evaluated and detected in damaged cells. Using tissue microarrays built from pre- and post-treatment human HGS-OvC tissue samples with accompanying clinical data, we quantified post-treatment hallmarks of senescence including reduced cell proliferation weeks after chemotherapy. Importantly, p16INK4A expression in pretreatment HGS-OvC samples correlated with increased patients survival, suggesting for the first time that senescence-competence in human cancer cells may have a beneficial impact on treatment outcomes for patients. In order to guide the potential improvement of existing human therapies via pharmacological senescence manipulation, our results suggests that it is important to determine for many types of human cancer whether treatment-induced senescence positively or negatively impacts disease progression and patient survival.