Chronic kidney disease: a clinical model of premature aging.
Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population.
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. peter.stenvinkel@ki.se
Peter
P
Stenvinkel
Tobias E
TE
Larsson
D000375:Aging / Q000502:physiology; D019588:Aging, Premature / Q000209:etiology* / Q000517:prevention & control; D016922:Cellular Senescence; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology; D058685:Genetic Pleiotropy; D005966:Glucuronidase / Q000502:physiology; D006801:Humans; D007249:Inflammation; D000090265:Klotho Proteins; D008954:Models, Biological; D051436:Renal Insufficiency, Chronic / Q000150:complications*
D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
Chronic kidney disease; aging; cardiovascular disease; inflammation; klotho; mammalian target of rapamycin (mTOR); oxidative stress; phosphate