RESUMO
The kidney is a metabolically active organ that requires energy to drive processes such as tubular reabsorption and secretion, and shows a decline in function with advancing age. Various molecular mechanisms, including genomic instability, telomere attrition, inflammation, autophagy, mitochondrial function, and changes to the sirtuin and Klotho signalling pathways, are recognized regulators of individual lifespan and pivotal factors that govern kidney ageing. Thus, mechanisms that contribute to ageing not only dictate renal outcomes but also exert a substantial influence over life expectancy. Conversely, kidney dysfunction, in the context of chronic kidney disease (CKD), precipitates an expedited ageing trajectory in individuals, leading to premature ageing and a disconnect between biological and chronological age. As CKD advances, age-related manifestations such as frailty become increasingly conspicuous. Hence, the pursuit of healthy ageing necessitates not only the management of age-related complications but also a comprehensive understanding of the processes and markers that underlie systemic ageing. Here, we examine the hallmarks of ageing, focusing on the mechanisms by which they affect kidney health and contribute to premature organ ageing. We also review diagnostic methodologies and interventions for premature ageing, with special consideration given to the potential of emerging therapeutic avenues to target age-related kidney diseases.
Assuntos
Envelhecimento , Insuficiência Renal Crônica , Humanos , Envelhecimento/fisiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/patologia , Proteínas Klotho , Autofagia/fisiologia , Sirtuínas/metabolismo , Sirtuínas/fisiologia , Glucuronidase/metabolismo , Glucuronidase/genética , Glucuronidase/fisiologia , Rim/patologia , Rim/fisiopatologia , Rim/metabolismo , Instabilidade Genômica , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Nefropatias/patologia , Mitocôndrias/metabolismoRESUMO
La glucuronoconjugación es un proceso de gran importancia en el metabolismo de xenobióticos y sustancias endógenas, facilitando su excreción por parte del organismo. Durante mucho tiempo ha sido aceptado que los metabolitos derivados de esta vía no poseían carácter activo o reactivo. Sin embargo, en los últimos años han surgido evidencias que ponen en duda aquella creencia, con especial referencia a los acilglucurónidos de los ácidos aril 2-propiónicos, cuya inestabilidad in vivo bajo condiciones fisiológicas ha demostrado tener implicancias inmunotoxicológicas potenciales a través de su unión irreversible a las proteínas (aductos). Esta revisión considera los aspectos que han modificado la percepción de la glucuronoconjugación como una vía sin importancia toxicológica y clínica para el organismo. Por lo tanto, la pregunta que debería ser contestada podría ser: es la glucuronoconjugación una vía de producción de sustancias tóxicas tanto como un mecanismo de detoxificación?