RESUMEN
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by nuclear envelope alterations that lead to accelerated aging and premature death. Several studies have linked health and longevity to cell-extrinsic mechanisms, highlighting the relevance of circulating factors in the aging process as well as in age-related diseases. We performed a global plasma proteomic analysis in two preclinical progeroid models (LmnaG609G/G609G and Zmpste24-/- mice) using aptamer-based proteomic technology. Pathways related to the extracellular matrix, growth factor response and calcium ion binding were among the most enriched in the proteomic signature of progeroid samples compared to controls. Despite the global downregulation trend found in the plasma proteome of progeroid mice, several proteins associated with cardiovascular disease, the main cause of death in HGPS, were upregulated. We also developed a chronological age predictor using plasma proteome data from a cohort of healthy mice (aged 1-30 months), that reported an age acceleration when applied to progeroid mice, indicating that these mice exhibit an "old" plasma proteomic signature. Furthermore, when compared to naturally-aged mice, a great proportion of differentially expressed circulating proteins in progeroid mice were specific to premature aging, highlighting secretome-associated differences between physiological and accelerated aging. This is the first large-scale profiling of the plasma proteome in progeroid mice, which provides an extensive list of candidate circulating plasma proteins as potential biomarkers and/or therapeutic targets for further exploration and hypothesis generation in the context of both physiological and premature aging.
Asunto(s)
Envejecimiento Prematuro , Progeria , Humanos , Ratones , Animales , Progeria/metabolismo , Envejecimiento Prematuro/genética , Proteómica , Proteoma/metabolismo , Secretoma , Lamina Tipo A/genética , Lamina Tipo A/metabolismoRESUMEN
La Biblioteca Dr. Laureano Rivas Miguez desde sus inicios en 1.902 ha acompañado a los profesionales de la salud del Hospital de Niños en la tarea de un constante perfeccionamiento. Cabe destacar la colaboración con la Revista del Hospital a través de su historia. En la búsqueda de esta historia hemos recopilado los nombres de aquellos que se han ocupado de mantener viva la obra de Laureano.
The MD. Laureano Rivas Miguez Library since its inception in 1902 has accompanied the health professionals of the Children's Hospital in the task of constant improvement. Noteworthy is the collaboration with the hospital magazine through its history. In the search of our history we have compiled the names of those who have been busy keeping Laureano's work alive.