Cellular senescence, senescence-associated secretory phenotype, and chronic kidney disease

Abstract

Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. The kidney undergoes age-related alterations in both structure and function. To date, a comprehensive analysis of cellular senescence and senescence-associated secretory phenotype (SASP) in CKD is lacking. Hence, this review mainly discusses the relationship between the two phenomena to show the striking similarities between SASP and CKD-associated secretory phenotype (CASP). It has been reported that replicative senescence, stress-induced premature ageing, and epigenetic abnormalities participate in the occurrence and development of CKD. Genomic damage and external environmental stimuli cause increased levels of oxidative stress and a chronic inflammatory state as a result of irreversible cell cycle arrest and low doses of SASP. Similar to SASP, CASP factors activate tissue repair by multiple mechanisms. Once tissue repair fails, the accumulated SASP or CASP species aggravate DNA damage response (DDR) and cause the senescent cells to secrete more SASP factors, accelerating the process of cellular ageing and eventually leading to various ageing-related changes. It is concluded that cellular senescence and SASP participate in the pathological process of CKD, and correspondingly CKD accelerated the progression of cell senescence and the secretion of SASP. These results will facilitate the integration of these mechanisms into the care and management of CKD and other age-related diseases.

Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages

“…2 C). Interestingly, even non-endothelial, non-macrophagic cells showed increased expression of p21 and TGFβ confirming that even kidney specific cell types can harbour a senescent and pro-inflammatory phenotype [39] , [40] , [41] . However, these data indicate that ECs and macrophages are SASP-carriers in vivo in HG-M kidneys.…”

“…Regarding the first result, renal senescence has recently been described as a complex phenomenon in both physiological and pathological conditions [39] , [40] . In a mouse model of automated clearance, the renin-angiotensin-aldosterone system (RAAS) was among those most strongly affected by SC removal, indicating that SC accumulation in this organ may involve systemic consequences that go beyond low-grade inflammation [10] , [39] .…”

Senescence of alveolar stem cells drives progressive pulmonary fibrosis

“…The senescence-associated secretory phenotype (SASP) has been shown to promote cell proliferation (85)(86)(87), stimulate cell motility (invasion, migration) (88-90), regulate cell differentiation (32,(88)(89)(90), and affect leukocyte infiltration (91)(92)(93), all of which serve important roles in repair following acute injury yet is a likely contributor to IPF pathogenesis. We show that a SASP gene expression signature is present within AT2 cells of the IPF lung and is induced following Sin3a loss in mouse AT2 cells.…”

Network analysis of membranous glomerulonephritis based on metabolomics data

“…It was demonstrated that the urinary excretion of nicotinamide and its metabolites was significantly lower in PAN-treated rats compared with control rats. It has been reported that a number of CKD-associated secretory phenotype proteins, including transforming growth factor-β (TGF-β), are involved in the early and late stages of renal wound healing in CKD ( 51 – 53 ). TGF-β1 appears to serve an important role in mediating the hypertrophic and fibrotic/sclerotic manifestations of DN ( 53 ).…”

“…It has been reported that a number of CKD-associated secretory phenotype proteins, including transforming growth factor-β (TGF-β), are involved in the early and late stages of renal wound healing in CKD ( 51 – 53 ). TGF-β1 appears to serve an important role in mediating the hypertrophic and fibrotic/sclerotic manifestations of DN ( 53 ). The protein sirtuin 1 (SIRT1; a class III histone deacetylase) is able to inhibit TGF-β1-induced apoptosis in glomerular mesangial cells through the deacetylation of mothers against decapentaplegic homolog 7 ( 54 ).…”