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Cellular Senescence in Chronic Kidney Disease


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Posted 11 October 2017 - 10:46 AM


There is good evidence for the growing number of senescent cells present in old tissues to be an important root cause of fibrosis, the breakdown of normal regenerative processes that results in scar-like structures in place of functional tissue. Chronic kidney disease is one of a number of age-related condition driven by fibrosis, all of which presently lack effective forms of treatment, capable of significantly turning back the progression of fibrosis. Fortunately, change is coming: researchers are exploring the link between fibrotic diseases and cellular senescence with an eye to producing new classes of treatment. Numerous approaches to the targeted removal of senescent cells are presently under development. The first and simplest of them are already entering human trials. I expect to see considerable progress in the treatment of fibrosis in the years ahead.

The continuous accumulation of senescent cells leads to the age-related deterioration of vital organs and thus constitutes an organism's ageing process. Correspondingly the therapeutic removal of senescent cells can improve health and prolong lifespan. Compared with young people, the elderly population not only is more susceptible to kidney damage but also shows more severe clinical manifestations and a lower likelihood of recovery of renal function. Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. Along with the process of ageing, the kidney shows certain types of changes for which specific findings are lacking. The ageing kidney and CKD share a great number of similarities in both structural and functional changes.

CKD is a frequent independent risk factor for renal failure and other age-related diseases. CKD is a complex pathological process mainly involving oxidative stress, inflammation, autophagy, apoptosis, and epigenetics. Recently, cellular senescence has become an increasingly popular and extensively studied topic because of its role in the occurrence and development of CKD. In CKD, the expression levels of senescence-associated β-galactosidase (SA-β-gal) and cell cycle inhibitor p16 protein were significantly increased in the glomeruli, tubules and interstitium, suggesting that the process of cellular senescence occurs in CKD. Many factors involved in the progress of CKD, such as urinary toxins, infections, dialysis treatment, and excessive activation of the renin-angiotensin system, can cause diverse types of DNA damage response (DDR) and accelerate the ageing process. The role of cellular senescence in CKD cannot be ignored.

When cells become senescent, they remain metabolically active and undergo widespread gene expression changes, secreting certain factors and changing the surrounding environment. This is the senescence-associated secretory phenotype (SASP), consisting of all types of cytokines, chemokines, growth factors, and proteases. In the course of kidney diseases, several cell types in the kidney experience cellular senescence and secrete a large number of factors that are collectively defined as the CKD-associated secretory phenotype (CASP). It has been demonstrated that CASP and SASP have prominent similarities, which may act as an essential medium mediating the interaction between CKD and cellular senescence.

Although there is a striking resemblance between SASP and CASP in terms of their features of up-regulation and the species involved, there remain many gaps in the understanding of the complex role of cellular senescence and SASP in CKD and other age-related diseases. It is beneficial to establish their mechanisms in the pathogenesis and progression of CKD. Therefore, the common process of cellular senescence and SASP is considered a treatment target for CKD and other age-related diseases.

Link: https://doi.org/10.1...ncotarget.17327


View the full article at FightAging




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