Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation
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Summary: Although chronological donor age is the most potent predictor of long‐term outcome after renal transplantation, it does not incorporate individual differences of the aging‐process itself. We therefore hypothesized that an estimate of biological organ age as derived from markers of cellular senescence in zero hour biopsies would be of higher predictive value. Telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) were assessed in pre‐implantation biopsies of 54 patients and the association of these and various other clinical parameters with serum creatinine after 1 year was determined. In a linear regression analysis, CDKN2A turned out to be the best single predictor followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values for serum creatinine 1 year after transplantation. We conclude that the molecular aging marker CDKN2A in combination with chronological donor age predict renal allograft function after 1 year significantly better than chronological donor age alone.
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Senescent cells accumulate exponentially with ageing in different organs and tissues in model organisms and humans.
“Studies have shown that senescent cells accumulate exponentially with ageing in different organs and tissues, both in model organisms and in humans97–100.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [100]
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Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
Wolfe, R. A., Ashby, V. B., Milford, E. L., OJO, A. O., Ettenger, R. E., Agodoa, L. Y. C., Held, P. J., & Port, F. K. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912023412303 · Cited by 5,370 · see citing works
Telomere measurement by quantitative PCR
Cawthon, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e47 · Cited by 3,492 · see citing works
The Banff 97 working classification of renal allograft pathology
Racusen, L. C., Solez, K., Colvin, R. B., Bonsib, S. M., de Castro, M. C. R., Cavallo, T., Croker, B. P., Demetris, A. J., Drachenberg, C. B., Fogo, A. B., et al. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00299.x · Cited by 3,026 · see citing works
Accelerated telomere shortening in response to life stress
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407162101 · Cited by 3,002 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457 · see citing works
Herbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344 · see citing works
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106 · see citing works
Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
Molofsky, A. V., Slutsky, S. G., Joseph, N. M., He, S., Pardal, R., Krishnamurthy, J., Sharpless, N. E., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature05091 · Cited by 972 · cited 2× · see citing works
“Also in the neuronal and hematopoetic systems, similar findings suggest a major role of p16INK4a in the lowering of renewal capacity and, furthermore, a decrease in function (Janzen et al ., 2006; Molofsky et al., 2006).”
BackgroundHayflick, his limit, and cellular ageing
Shay, J. W., & Wright, W. E. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036093 · Cited by 764 · see citing works
Zindy, F., Quelle, D. E., Roussel, M. F., & Sherr, C. J. (1997) · Oncogene · doi:10.1038/sj.onc.1201178 · Cited by 574 · see citing works
Telomere Length in the Newborn
Okuda, K., Bardeguez, A., Gardner, J. P., Rodriguez, P., Ganesh, V., Kimura, M., Skurnick, J., Awad, G., & Aviv, A. (2002) · Pediatric Research · doi:10.1203/00006450-200209000-00012 · Cited by 507 · see citing works
Replicative Senescence: An Old Lives' Tale?
Campisi, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81023-5 · Cited by 434 · see citing works
When cells get stressed: an integrative view of cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420663 · Cited by 404 · see citing works
Melk, A., Schmidt, B. M. W., Takeuchi, O., Sawitzki, B., Rayner, D. C., & Halloran, P. F. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00438.x · Cited by 362 · see citing works
Frei, U. A., Noeldeke, J., Machold-Fabrizii, V., Arbogast, H. P., Margreiter, R., Fricke, L., Voiculescu, A., Kliem, V., Ebel, H., Albert, U., et al. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.02014.x · Cited by 356 · see citing works
Stengel, B. (2003) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfg233 · Cited by 266 · see citing works
Analysis of factors that affect outcome of primary cadaveric renal transplantation in the UK
Morris, P. J., Johnson, R., Fuggle, S. V., et al. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01104-6 · Cited by 249 · see citing works
Telomere Shortening in Kidneys with Age
MELK, A., RAMASSAR, V., HELMS, L. M. H., MOORE, R., RAYNER, D., SOLEZ, K., & HALLORAN, P. F. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v113444 · Cited by 189 · see citing works
Time Dependency of Factors Affecting Renal Allograft Survival
Prommool, S., Jhangri, G. S., Cockfield, S. M., & Halloran, P. F. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v113565 · Cited by 180 · see citing works
Evaluation of the Eurotransplant Senior Program. The Results of the First Year
Smits, J. M., Persijn, G. G., van Houwelingen, H. C., et al. (2002) · American Journal of Transplantation · doi:10.1034/j.1600-6143.2002.20713.x · Cited by 176 · see citing works
Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program
Edwards, M. G., Anderson, R. M., Yuan, M., Kendziorski, C. M., Weindruch, R., & Prolla, T. A. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-80 · Cited by 174 · see citing works
Expanding the donor pool to increase renal transplantation
Cohen, B., Smits, J. M., Haase, B., et al. (2004) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh506 · Cited by 165 · see citing works
Sis, B., Tasanarong, A., Khoshjou, F., Dadras, F., Solez, K., & Halloran, P. F. (2007) · Kidney International · doi:10.1038/sj.ki.5002039 · Cited by 159 · see citing works
Cyclosporine A induces senescence in renal tubular epithelial cells
Jennings, P., Koppelstaetter, C., Aydin, S., Abberger, T., Wolf, A. M., Mayer, G. J., & Pfaller, W. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00005.2007 · Cited by 155 · see citing works
Self-citationMelk, A., Schmidt, B. M. W., Vongwiwatana, A., Rayner, D. C., & Halloran, P. F. (2005) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.00846.x · Cited by 154 · see citing works
The impact of donor age on the results of renal transplantation
Oppenheimer, F. (2004) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh1008 · Cited by 117 · see citing works
THE KIDNEYS THAT NOBODY WANTED
Lee, C. M., Scandling, J. D., Shen, G. K., et al. (1996) · Transplantation · doi:10.1097/00007890-199612270-00027 · Cited by 103 · see citing works
Telomere Shortening and Cellular Senescence in a Model of Chronic Renal Allograft Rejection
Joosten, S. A., van Ham, V., Nolan, C. E., Borrias, M. C., Jardine, A. G., Shiels, P. G., van Kooten, C., & Paul, L. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63926-0 · Cited by 102 · see citing works
Siddiqi, N., McBride, M., & Hariharan, S. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00589.x · Cited by 95 · see citing works
Eurotransplant kidney allocation system (ETKAS): rationale and implementation
Mayer, G. J., & Persijn, G. G. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfi269 · Cited by 75 · see citing works
Self-citationThe role of replicative senescence in chronic allograft nephropathy
Ferlicot, S., Dürrbach, A., Bâ, N., Desvaux, D., Bédossa, P., & Paradis, V. (2003) · Human Pathology · doi:10.1016/s0046-8177(03)00340-x · Cited by 65 · see citing works
Lloyd, A. C. (2002) · Nature Cell Biology · doi:10.1038/ncb0202-e25 · Cited by 62 · see citing works
Incidence and prevalence of ESRD
(1999) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(99)80014-6 · Cited by 33 · see citing works
Histologic Assessment of Donor Kidneys and Graft Outcome: Multivariate Analyses
Arias, L. F., Blanco, J., Sánchez-Fructuoso, A. I., et al. (2007) · Transplantation Proceedings · doi:10.1016/j.transproceed.2007.01.085 · Cited by 25 · see citing works
Gjertson, D. W. (2004) · PubMed · Cited by 21 · see citing works
Correlation between the Banff 97 classification of renal allograft biopsies and clinical outcome
Tanaka, T. T., Kyo, M., Kokado, Y., et al. (2004) · Transplant International · doi:10.1111/j.1432-2277.2004.tb00405.x · Cited by 18 · see citing works
Correlation between the Banff 97 classification of renal allograft biopsies and clinical outcome
Kokado, Y., Suzuki, K., Hasumi, M., et al. (2004) · Transplant International · doi:10.1007/s00147-003-0660-9 · Cited by 17 · see citing works
Domínguez, J. I. B., Kompatzki, Á., Velasco, A., et al. (2005) · Transplantation Proceedings · doi:10.1016/j.transproceed.2005.09.029 · Cited by 4 · see citing works
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363 · see citing works
Measuring biological aging in humans: a quest
Ferrucci, L., Gonzalez‐Freire, M., Fabbri, E., Simonsick, E., Tanaka, T., Moore, Z., Salimi, S., Sierra, F., & de Cabo, R. (2020) · Aging Cell · doi:10.1111/acel.13080 · Cited by 781 · see citing works
Liu, Y., Sanoff, H. K., Cho, H., Burd, C. E., Torrice, C., Ibrahim, J. G., Thomas, N. E., & Sharpless, N. E. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00489.x · Cited by 509 · see citing works
Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model
Burd, C. E., Sorrentino, J. A., Clark, K. S., Darr, D. B., Krishnamurthy, J., Deal, A. M., Bardeesy, N., Castrillon, D. H., Beach, D. H., & Sharpless, N. E. (2013) · Cell · doi:10.1016/j.cell.2012.12.010 · Cited by 419 · see citing works
Cellular senescence in renal ageing and disease
Sturmlechner, I., Durik, M., Sieben, C. J., Baker, D. J., & van Deursen, J. M. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.183 · Cited by 345 · see citing works
The number of p16INK4a positive cells in human skin reflects biological age
Waaijer, M. E. C., Parish, W. E., Strongitharm, B. H., van Heemst, D., Slagboom, P. E., de Craen, A. J. M., Sedivy, J. M., Westendorp, R. G. J., Gunn, D. A., & Maier, A. B. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00837.x · Cited by 264 · see citing works
Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., & Kirkland, J. L. (2020) · Cancers · doi:10.3390/cancers12082134 · Cited by 235 · see citing works
“Few studies have directly assessed the relationship with senescence and surgical outcomes; however, p16 expression is negatively correlated with liver regeneration after hepatectomy in older patients [83] and the molecular aging marker CDKN2A has been shown to predict renal allograft function after 1 year in renal tra…”
BackgroundMolecular mechanisms of renal aging
Schmitt, R., & Melk, A. (2017) · Kidney International · doi:10.1016/j.kint.2017.02.036 · Cited by 235 · see citing works
Diekman, B. O., Sessions, G. A., Collins, J. A., Knecht, A. K., Strum, S. L., Mitin, N. K., Carlson, C. S., Loeser, R. F., & Sharpless, N. E. (2018) · Aging Cell · doi:10.1111/acel.12771 · Cited by 158 · see citing works
Shiels, P. G., McGlynn, L. M., MacIntyre, A., Johnson, P. C. D., Batty, G. D., Burns, H., Cavanagh, J., Deans, K. A., Ford, I., McConnachie, A., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022521 · Cited by 143 · see citing works
Liu, J., Yang, J.-R., Chen, X.-M., Cai, G.-Y., Lin, L.-R., & He, Y.-N. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00096.2014 · Cited by 117 · see citing works
The role of epigenetics in renal ageing
Shiels, P. G., McGuinness, D., Eriksson, M., Kooman, J. P., & Stenvinkel, P. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.78 · Cited by 114 · see citing works
Gadalla, S. M., Wang, T., Haagenson, M., Spellman, S. R., Lee, S. J., Williams, K. M., Wong, J. Y., De Vivo, I., & Savage, S. A. (2015) · JAMA · doi:10.1001/jama.2015.7 · Cited by 95 · see citing works
Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage
Franzin, R., Stasi, A., Fiorentino, M., Stallone, G., Cantaluppi, V., Gesualdo, L., & Castellano, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00734 · Cited by 93 · see citing works
Cheng, H., Fan, X., Lawson, W. E., Paueksakon, P., & Harris, R. C. (2015) · Kidney International · doi:10.1038/ki.2015.69 · Cited by 89 · see citing works
Phillips, A. C., Robertson, T., Carroll, D., Der, G., Shiels, P. G., McGlynn, L., & Benzeval, M. (2013) · Psychosomatic Medicine · doi:10.1097/psy.0b013e318289e6b5 · Cited by 55 · see citing works
Pustavoitau, A., Barodka, V., Sharpless, N. E., Torrice, C., Nyhan, D., Berkowitz, D. E., Shah, A. S., Bandeen Roche, K. J., & Walston, J. D. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2015.12.003 · Cited by 36 · see citing works
Domański, L., Kłoda, K., Kwiatkowska, E., Borowiecka, E., Safranow, K., Drozd, A., Ciechanowicz, A., & Ciechanowski, K. (2015) · BMC Nephrology · doi:10.1186/s12882-015-0014-8 · Cited by 32 · see citing works
Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms: Table 1.
Burd, C. E., Gill, M. S., Niedernhofer, L. J., Robbins, P. D., Austad, S. N., Barzilai, N., & Kirkland, J. L. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw112 · Cited by 28 · see citing works
- Authors
- Koppelstaetter, C., Schratzberger, G., Perco, P., Hofer, J., Mark, W., Öllinger, R., Oberbauer, R., Schwarz, C., Mitterbauer, C., Kainz, A., Karkoszka, H., Wiecek, A., Mayer, B., & Mayer, G.
- Affiliations
- Innsbruck Medical University (AT)
- Krankenhaus der Elisabethinen (AT)
- Medical University of Vienna (AT)
- Medical University of Silesia (PL)
- EmergenTec (Austria) (AT)
- Corresponding author
- Mayer, Gert
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2008-07-10
- Volume
- 7
- Issue
- 4
- Pages
- 491-497
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2088934391
- Cited by
- 124
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 14 · 2016: 15 · 2015: 14 · 2014: 8 · 2013: 16 · 2012: 6
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- cellular senescence, kidney transplantation, biological age, telomere length, CDKN2A, p16INK4a, p21, donor age, serum creatinine, allograft function, cell cycle inhibitors
- MeSH terms
- Adult, Aging, Biopsy, Creatinine, Demography, Female, Humans, Kidney, Male, Middle Aged, Postoperative Period, Regression Analysis, Time Factors, Tissue Donors, Transplantation, Homologous, Biomarkers, Kidney Transplantation, Telomere, Treatment Outcome, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21
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