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{{DISPLAYTITLE:Targeting kidney cell senescence: a new paradigm for the treatment of chronic kidney disease?}}
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|title=Targeting kidney cell senescence: a new paradigm for the treatment of chronic kidney disease? - Top Italian Scientists Journal
|description=Cellular senescence is a condition where cells undergo a permanent cell cycle arrest, accompanied by a unique set of functional and morphological changes.
|keywords=chronic kidney disease, kidney cell senescence.
|citation_author=Garibotto, Giacomo; Esposito, Pasquale; Picciotto, Daniela; Verzola, Daniela; Costigliolo, Francesca; Zanetti, Valentina; Saio, Michela; Russo, Elisa; Viazzi, Francesca             
|citation_journal_title=Top Italian Scientists Journal 
|citation_publication_date=2024/06/06 
|citation_title=Targeting kidney cell senescence: a new paradigm for the treatment of chronic kidney disease?
|citation_keywords=chronic kidney disease; kidney cell senescence.
|citation_publisher=Top Italian Scientists
|citation_volume=1
|citation_issue=3
|citation_doi=10.62684/FJDT9733
|citation_issn=3033-5132
|}}
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| '''Published'''
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| June 6, 2024
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| '''Title''' 
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| style="width:200px;" | Targeting kidney cell senescence: a new paradigm for the treatment of chronic kidney disease?
|- 
| '''Authors'''
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|   Giacomo Garibotto, Pasquale Esposito, Daniela Picciotto, Daniela Verzola, Francesca Costigliolo, Valentina Zanetti, Michela Saio, Elisa Russo, Francesca Viazzi 
|-
| '''DOI'''
|-
| [https://doi.org/10.62684/FJDT9733 10.62684/FJDT9733]
|-
| '''Keywords'''
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| chronic kidney disease; kidney cell senescence.
|-
| '''Downloads'''
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|  style="text-align: center;" | [[File:PDF_file_icon.png|center|50px|'''Download PDF'''|link=****]]
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'''[https://topitalianscientists.org/tis/21921/Giacomo_Garibotto_-_Top_Italian_Scientist_in_Clinical_Sciences Giacomo Garibotto]'''<sup>(a)</sup>, '''Pasquale Esposito'''<sup>(a,b)</sup>, '''Daniela Picciotto'''<sup>(b)</sup>, '''Daniela Verzola'''<sup>(a)</sup>, '''Francesca Costigliolo'''<sup>(b)</sup>, '''Valentina Zanetti'''<sup>(a,b)</sup>, '''Michela Saio'''<sup>(b)</sup>, '''Elisa Russo'''<sup>(a,b)</sup>, '''Francesca Viazzi'''<sup>(a,b)</sup> 

Department of Internal Medicine, University of Genova <sup>(a)</sup>, Division of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genova <sup>(b)</sup>

''Correspondence to'': Giacomo Garibotto MD, Department of Internal Medicine, Università degli Studi di Genova, Viale Benedetto XV, 6, 16132 Genova, Italy. email:gari@unige.it

==Abstract==
Cellular senescence is a condition where cells undergo a permanent cell cycle arrest, accompanied by a unique set of functional and morphological changes. While initial studies of senescence have largely focused on its role as a barrier to extended cell division and tumorigenesis, in recent years cell senescence has emerged as an important driver of aging and age-related disease in different tissues, including the kidney. Accelerated cell senescence may decrease kidney repair capacity because of cell cycle arrest; in addition cell senescence promotes glomerulosclerosis and tubulointerstitial fibrosis via the production and release of proinflammatory and matrix-degrading molecules. Although almost all glomerular and tubular cells may undergo senescent changes, the glomerular podocytes and proximal tubule cells are the most commonly affected cells. In these days, treating cell senescence is moving his steps from the preclinical to the clinical stage. While cell senescence appears to be well accepted as a new mechanism for kidney damage and chronic kidney disease [CKD] progression, there still are many unanswered questions regarding how to dectect it in kidney biopsies, which is prognostic meaning of individual kidney senescnce markers, which the role of different cells involved, as well as the efficacy of the emerging senescence-targeted therapies on the progression and complications of CKD.

==Declarations==
=== Conflict of Interest ===
The Authors declare that there is no conflict of interest.

== References ==
<ol class="references">
<li>Hayflick, L.; Moorhead, P.S. The serial cultivation of human diploid cell strains.[1961] Exp. Cell. Res.  25:585-621</li>
<li>Melk, A.; Schmidt, B.M.; Takeuchi, O., et al. [2004] Expression of p16INKA and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int. 65: 510–520. </li>
<li>Hampel, B.; Wagner, M.; Teis, D.; et al. [2005]. Apoptosis resistance of senescent human fibroblasts is correlated with the absence of nuclear IGFBP-3. Aging Cell. 4(6):325-30. </li>
<li>Coppé, J.P.; Patil, C.K.; Rodier, F.; et al. [2010]. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS One  5(2):e9188.</li>
<li>Ben-Porath, I. & Weinberg R.A.[2004] When cells get stressed: an integrative view of cellular senescence. J Clin Invest 113: 8–13</li>
<li>Clemens, A.; Schmitt, C.A.;Wang,B.; Demaria, M.[2022]. Senescence and cancer - role and therapeutic opportunities Nat. Rev. Clin. Oncol.19:619-636.doi: 10.1038/s41571-022-00668-4.</li>
<li>Docherty, M.H.; O’ Sullivan, E. D.; Bonventre, J. V.; et al. [2019]. Cellular Senescence in the Kidney. J. Am. Soc. Nephrol. 30: 726–736. </li>
<li>Denic, A.; Rule, A.D.; Glassock, R.J. [2022]. Healthy and unhealthy aging on kidney structure and function: human studies.Curr. Opin. Nephrol. Hypertens. 31:228-234. </li>
<li>Childs, B.G.; Durik, M.; Baker, D.J.; et al. [2015]. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat. Med. 21:1424-35. </li>
<li>Safwan-Zaiter, H.; Wagner, N.; Michiels, J.F.; et al. [2022]. Dynamic Spatiotemporal Expression Pattern of the Senescence-Associated Factor p16INKA in Development and Aging. Cells 11:541. </li>
<li>Muñoz-Espín, D.; Serrano, M.; [2014]. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. 15, 482–496.</li>
<li>D'Adda di Fagagna, F.; Reaper, P.M.; Clay-Farrace, L.; et al. [2003]. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 426:194-198.</li>
<li>Yang, L.; Besschetnova, T.Y.; Brooks, C.R.; et al. [2010] Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 16:535–543.</li>
<li>Westhoff, J. H.; Hilgers, K.F.; Steinbach, M.P.; et al. [2008]. Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. Hypertension 52:123-9. </li>
<li>Manjeri, A.; Venkatachalam, K.A.; Griffin, R.; Lang, H. ; Geng, P. S.& Bidani, A.K. Acute kidney injury: a springboard for progression in chronic kidney disease [2010] Am. J. Physiol. Renal. Physiol. 298:F1078-94.</li>
<li>Liu, J.; Yang, J.R.; He, Y.N.; Cai, G.Y.; Zhang, J.G.; Lin, L.R.; Xiao, H.S.[2012] Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy. Transl. Res. 159, 454–463.</li>
<li>Verzola, D.; Saio, M.; Picciotto, D.; Viazzi, F.; Russo, E.; Cipriani, L.; [2021].Cellular Senescence Is Associated with Faster Progression of Focal Segmental Glomerulosclerosis. Am. J. Nephrol. 51, 950–958.</li>
<li>Verzola, D.; Gandolfo, M.T.; Gaetani, G.; et al. [2008]. Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. Am. J. Physiol. Renal Physiol. 295:F1563-73.</li>
<li>Sis, B.; Tasanarong, A.; Dadras, F.; Solez, K.; Halloran, P.F. [2007] Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease. Kidney Int.  71, 218–226.</li>
<li>Krishna, D.R.; Sperker, B.; Fritz, P.; Klotz, U. Does pH 6 β-galactosidase activity indicate cell senescence? Mech. Ageing Dev. [1999], 109, 113–123. https://doi.org/10.1016/S0047-6374(99)00031-7.</li>
<li>Debacq-Chainiaux, F.; Erusalimsky, J.,D.; Campisi, J.; Toussaint, O. [2009]  Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat. Protoc. 4, 1798–1806. https://doi.org/10.1038/nprot.2009.191</li>
<li>Jannone, G.; Rozzi, M.; Najimi, M.; Decottignies, A.; & Sokal, E.M.; [2020] An Optimized Protocol for Histochemical Detection of Senescence-associated Beta-galactosidase Activity in Cryopreserved Liver Tissue J. Histochem. Cytochem. 68:269-278. doi: 10.1369/0022155420913534</li>
<li>Esposito, P.; Picciotto, D.;Verzola, D.; Garibotto, G.; Parodi, E.L.; Sofia, A.; Costigliolo, F.; Gaggero, G.; Zanetti, V.; Saio, M.; Viazzi, F.; [2024] SA-β-Gal in Kidney Tubules as a Predictor of Renal Outcome in Patients with Chronic Kidney Disease. J. Clin. Med. 13:322. doi: 10.3390/jcm13020322.</li>
<li>Wiggins, J.E. Aging in the glomerulus. [2012] J. Gerontol. A. Biol. Sci. Med. Sci. 67:1358–1364. doi: 10.1093/gerona/gls157</li>
<li>Shankland, S.J.; Rule, A.D.; Kutz, J.N.; Pippin, J.W.; Wessely, O. [2023] Podocyte Senescence and Aging. Kidney360  4:1784-1793. doi: 10.34067/KID.0000000000000284. </li>
<li>Hurcombe, J.A.; Hartley, P.; Lay, A. C.; et al. [2019]. Podocite GSK3 is an evolutionarily conserved critical regulator of kidney function. Nat. Commun. 10:403.</li>
<li>Garibotto, G.; Carta, A.; Picciotto, D.; Viazzi, F.; Verzola, D.[2017] Toll-like receptor-4 signaling mediates inflammation and tissue injury in diabetic nephropathy. J. Nephrol. 30, 719–727. https://doi.org/10.1007/s40620-017-0432-8.</li>
<li>Verzola, D.; Cappuccino, L.; D'Amato, E.; Villaggio, B.; Gianiorio, F.; Mij, M.; Simonato, A.; Viazzi, F.; Salvidio, G.; Garibotto, G. [2014] Enhanced glomerular Toll-like receptor 4 expression and signaling in patients with type 2 diabetic nephropathy and microalbuminuria. Kidney Int. 86:1229-43. doi: 10.1038/ki.2014.116. </li>
<li>Stenvinkel, P.; Larsson, T.E. [2013] Chronic Kidney Disease: A Clinical Model of Premature Aging. Am. J. Kidney Dis. 62:339–51.</li>
<li>Cardozo, L.F.M.F; Borges, N.A.; Ribeiro, M.; Yee-Moon Wang, A.;  Mafra, D.  [2023] Protect the Kidneys and Save the Heart Using the Concept of Food as Medicine J. Ren, Nutr.  33, Supplement S110–S117.</li>
<li>Wiese, G.N.; Biruete, A.; Stremke, E.R; Lindemann, S.R., Jannasch, A.; Moorthi, R.N. et al.[2023] Gut Microbiota and Uremic Retention Solutes in Adults With Moderate CKD: A 6-Day Controlled Feeding Study  J. Ren, Nutr.  34: 26–34. DOI: 10.1053/j.jrn.2023.06.011ù</li>
<li>Mitrović, M.; Stanković-Popović, V.; Tolinački, M.; Golićm, N.; Soković Bajić, S.; Veljović, K. Et al. [2022] The Impact of Synbiotic Treatment on the Levels of Gut-Derived Uremic Toxins, Inflammation, and Gut Microbiome of Chronic Kidney Disease Patients—A Randomized Trial  J. Ren, Nutr.  33;278–288.   DOI: 10.1053/j.jrn.2022.07.008</li>
<li>Baker, D.J. ; Wijshake, T. ; Tchkonia, T. ; et al. [2011]. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 479:232–236.</li>
<li>Roos, C.M. ; Zhang, B. ; Palmer, A.K. ; et al. [2016]. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15:973-7. </li>
<li>Baar, M.P.; Brandt, R.M.C.; Putavet, D.A.; et al. [2017]. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169: 132–147.</li>
<li>Baker, D.J. ; Childs, B.G. ; Durik, M. ; et al. [2016]. Naturally occurring p16INKA(Ink4a)-positive cells shorten healthy lifespan. Nature 530:184–189.</li>
<li>Wiggins, J.E.; Goyal, M.; Sanden, S.K.; et al. [2005] Podocyte hypertrophy, “adaptation,” and “decompensation” associated with glomerular enlargement and glomerulosclerosis in the aging rat: prevention by calorie restriction. J. Am. Soc. Nephrol.16:2953–2966. doi: 10.1681/ASN.2005050488.</li>
<li>Bordone, L.; Guarente, L.[2005] Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat. Rev. Mol. Cell. Biol. 6:298–305. doi: 10.1038/nrm1616</li>
<li>Sweetwyne, M.T.; Pippin, J.W.; Eng, D.G.;et al. [2017] The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age. Kidney Int. 91:1126–1145. doi: 10.1016/j.kint.2016.10.036</li>
<li>Liao, C.M.; Wulfmeyer, V.C.; Chen, R.; et al. [2022] Induction of ferroptosis selectively eliminates senescent tubular cells. Am. J. Transplant. 22:2158–2168. doi: 10.1111/ajt.17102</li>
<li>Brendon, L.N.; Chadban, S.G.; Demaio, A.L.; Johnson, D.W.; Perkovic, V.[2017] Chronic kidney disease and the global NCDs agenda. BMC Glob. Health  2, e000380.</li>
<li>Wang, H.; Naghavi, M.; Allen, C.; Barber, R.M.; Bhutta, Z.A.; Carter, A.; Casey, D.C.; Charlson, F.J.; Chen, A.Z.; Coates, M.; et al. [2016] GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1459–1544</li>
</ol>

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