Age-related morphological, cellular and molecular changes in renal fibrosis

Abstract

During the last 50 years the average age of the Uruguayan population has increased, coinciding with higher numbers of the population over 65 years old with chronic kidney disease. The pathological changes during ageing that affect kidney function are not very well understood. During ageing the kidney suffers morphological and functional changes, like interstitial fibrosis and glomerular sclerosis. These changes are the result of alterations that take place at the cellular level. Here, the cellular mechanisms that trigger interstitial fibrosis and glomerulosclerosis, including sustained inflammation, transition from epithelial to myofibroblastic cellular phenotype, and the mechanism involved in extracellular matrix production and progression of kidney fibrosis, will be discussed. We also consider the molecular cascades involved in fibrosis, with an emphasis on the transforming growth factor-beta1 (TGF-β1) signalling pathway that modulates the production of pro- and anti-fibrotic factors. We will also explore how TGF-β1 modulates non-coding small RNA (micro-RNA) expression, which is a powerful mechanism for gene regulation, and how the anti-ageing gene Klotho inhibits kidney fibrosis progression. Finally, alternative therapies that target pathways modulated by TGF-β1, micro-RNAs and activation of Klotho will be considered as precautionary measures to help to prevent age-related kidney disease.