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Kidney Week

Abstract: PO2481

Does Senescence Induce Muscle Wasting in CKD?

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms


  • Wang, Bin, Southeast University, Nanjing, Jiangsu, China
  • Huang, Ying, Emory University School of Medicine, Atlanta, Georgia, United States
  • Klein, Janet D., Emory University School of Medicine, Atlanta, Georgia, United States
  • Cai, Hui, Emory University School of Medicine, Atlanta, Georgia, United States
  • Wang, Xiaonan H., Emory University School of Medicine, Atlanta, Georgia, United States

Muscle wasting is a common complication of CKD and associated with higher mortality and morbidity. The mechanism of muscle wasting in uremia has been widely studied; however, uremic stress-induced senescence might be a missing connection between chronic kidney disease and muscle wasting. Senescent cells are capable of producing and secreting various growth and proinflammatory factors, cytokines, and chemokines, which is known as the S-ASP. We hypothesized that senescence and senescence associated secretary phenotype (S-ASP) play important roles in the CKD-induced muscle loss.


CKD mice were induced by 5/6 nephrectomy. Senescence was confirmed by using senescence associated beta gal (SA-βgal). The levels of S-ASP (interleukin 6 (IL-6), TNFα, TGFβ and IL-8) were measured by immunohistochemistry and ELISA. Senescence pathway markers p16, p21 and p53 were measured by Western blots. To limit senescence, dasatinib (5 mg/kg BW) + quercetin (50 mg/kg BW) (D&Q) were given by oral gavage 2 days per week for 8 weeks. Muscle function was measured with a grip force detector.


CKD stress-induced premature senescence phenomena have been evidenced in the skeletal muscle of uremic mice by 1) the increases in senescence pathway indicators p21 and p16, but not p53 protein; 2) phosphorylated histone H2AX (γH2AX, DNA damage marker); 3) the level of the senescence biomarker SA-β gal; and 4) S-ASP components present in the uremic muscle, which include high levels of interleukin 6 (IL-6), TNFα, TGFβ and IL-8. The D&Q treatment eliminated CKD-induced elevation of p21, p16 and γH2AX, abolished positive SA-β gal, and depressed the high levels of S-ASP cytokines. The muscle cross-sectional area was increased by D&Q treatment compared with the vehicle treatment in 5/6 nephrectomy mice. Skeletal muscle function was also improved with D&Q treatment in uremic mice.


Senescence and S-ASP are important factors in development of muscle wasting during CKD progression. Limiting senescence with D&Q ameliorates muscle wasting and improves muscle function. These results provide new approaches for developing therapeutic strategies to improve muscle health in chronic kidney diseases.


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