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411.
Marisa Ferreira-Marques André Carvalho Ana Catarina Franco Ana Leal Mariana Botelho Sara Carmo-Silva Rodolfo Águas Luísa Cortes Vasco Lucas Ana Carolina Real Carlos López-Otín Xavier Nissan Luís Pereira de Almeida Cláudia Cavadas Célia A. Aveleira 《Aging cell》2023,22(12):e13983
Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition that arises from a single nucleotide alteration in the LMNA gene, leading to the production of a defective lamin A protein known as progerin. The accumulation of progerin accelerates the onset of a dramatic premature aging phenotype in children with HGPS, characterized by low body weight, lipodystrophy, metabolic dysfunction, skin, and musculoskeletal age-related dysfunctions. In most cases, these children die of age-related cardiovascular dysfunction by their early teenage years. The absence of effective treatments for HGPS underscores the critical need to explore novel safe therapeutic strategies. In this study, we show that treatment with the hormone ghrelin increases autophagy, decreases progerin levels, and alleviates other cellular hallmarks of premature aging in human HGPS fibroblasts. Additionally, using a HGPS mouse model (LmnaG609G/G609G mice), we demonstrate that ghrelin administration effectively rescues molecular and histopathological progeroid features, prevents progressive weight loss in later stages, reverses the lipodystrophic phenotype, and extends lifespan of these short-lived mice. Therefore, our findings uncover the potential of modulating ghrelin signaling offers new treatment targets and translational approaches that may improve outcomes and enhance the quality of life for patients with HGPS and other age-related pathologies. 相似文献
412.
Abstract. The aim of this quantitative biogeographical analysis is to identify the existence of specific groups of pteridophytes with significantly similar distribution patterns (chorotypes) in the Iberian Peninsula, as well as to infer the environmental factors that may explain such groupings. We have applied a classification method to the pteridophyte species and have then tested the significance of the resulting groups. This allows the distinction of groups of species that occur together more frequently than expected at random from those which are just a product of the cluster analysis. The majority of the 113 pteridophyte species in the Iberian Peninsula are not distributed independently from each other, but eighteen chorotypes exist that are common to various species and three chorotypes that consist of one species each. Five species are distributed independently of the other species, and so their distribution areas overlap and segregate from the others at random. With the aim of finding a relation between the chorotypes identified and the processes that determine them, we investigated the possible incidence of certain environmental factors on the chorotype distributions by means of logistic regression. Factors that appear most frequently as possible causes of the distribution of the chorotypes are the water availability, climatic stress, availability of environmental energy, and disturbances caused by floods. Resumen . El objetivo de este análisis biogeográfico cuantitativo es identificar la posible existencia de grupos de especies de pteridófitos con patrones de distribución significantivamente similares (corotipos) en la Peninsula Ibérica, así como analizar los factores ambientales que explican tales grupos. Hemos aplicado un método de clasificatión biogeográfica de especies y después hemos comprobado la significación de los grupos resultantes. Esto nos ha permitido distinguir los grupos de especies que se asocian con más frecuencia de lo esperado por azar de aquellos grupos que se deben únicamente al análisis de agrupación. La mayoría de las 113 especies de pteridófitos en la Península Ibérica no se distribuyen independientemente unas de otras, sino que existen 18 corotipos que son comunes a varias especies y tres que están formados por una sola especie. Cinco especies se distribuyen independientemente de las restantes, y por tanto, sus áreas de distribución se solapan y se segregan con las demás al azar. Con objeto de encontrar una relación entre los corotipos identificados en el presente trabajo y los procesos que los determinan, investigamos por medio de regresiones logísticas la posible incidencia de ciertos factores ambientales sobre las distribuciones de los corotipos. Los factores que han aparecido más frecuentemente como posibles causas de las distribuciones de los corotipos son la disponibilidad de agua, el estrés climático, la energía ambiental disponible y los disturbios causados por las inundaciones. 相似文献