Skip to main content

Abstract

p53 is an extensively studied tumor suppressor that functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis, and other cellular responses in response to various forms of stress. Besides its major functions of cell-cycle arrest and apoptosis, p53 also plays an important role in regulating cellular senescence and organismal aging. Cellular senescence is a state of irreversible cell-cycle arrest, which has been associated both with aging and as a physiological antitumor response against oncogenic insults. Therefore, senescence is a potent mechanism through which p53 causes tumor growth suppression. However, the senescence response depends upon the level of p53 expression as well as the cellular context. In this chapter, we discuss the involvement of p53 in the process of aging and describe p53-mediated regulation of various cellular pathways that contribute to both senescence and aging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sherwood SW, Rush D, Ellsworth JL, Schimke RT. Proc Natl Acad Sci U S A. 1988;85:9086–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. Genes Dev. 2010;24:2463–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Romagosa C, Simonetti S, Lopez-Vicente L, Mazo A, Lleonart ME, Castellvi J, Ramon y Cajal S. Oncogene. 2011;30:2087–97.

    CAS  PubMed  Google Scholar 

  4. Alessio N, Squillaro T, Cipollaro M, Bagella L, Giordano A, Galderisi U. Oncogene. 2010;29:5452–63.

    CAS  PubMed  Google Scholar 

  5. Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, Benguria A, Zaballos A, Flores JM, Barbacid M, Beach D, Serrano M. Nature. 2005;436:642.

    CAS  PubMed  Google Scholar 

  6. Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE. J Clin Invest. 2004;114:1299–307.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Sharpless NE. Exp Gerontol. 2004;39:1751–9.

    CAS  PubMed  Google Scholar 

  8. Caldwell ME, DeNicola GM, Martins CP, Jacobetz MA, Maitra A, Hruban RH, Tuveson DA. Oncogene. 2012;31:1599–608.

    CAS  PubMed  Google Scholar 

  9. Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J. EMBO J. 2003;22:4212–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Hayflick L, Moorhead PS. Exp Cell Res. 1961;25:585–621.

    CAS  PubMed  Google Scholar 

  11. Kenyon C. Cell. 2005;120:449–60.

    CAS  PubMed  Google Scholar 

  12. Wang MC, O'Rourke EJ, Ruvkun G. Science. 2008;322:957–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kenyon CJ. Nature. 2010;464:504–12.

    CAS  PubMed  Google Scholar 

  14. Curran SP, Wu X, Riedel CG, Ruvkun G. Nature. 2009;459:1079–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C. Genetics. 2002;161:1101–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. Science. 2003;301:1387–91.

    CAS  PubMed  Google Scholar 

  17. Bartke A. Cell Cycle. 2008;7:3338–43.

    CAS  PubMed  Google Scholar 

  18. Yuan R, Tsaih SW, Petkova SB, Marin de Evsikova C, Xing S, Marion MA, Bogue MA, Mills KD, Peters LL, Bult CJ, Rosen CJ, Sundberg JP, Harrison DE, Churchill GA, Paigen B. Aging Cell. 2009;8:277–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kappeler L, De Magalhaes Filho C, Dupont J, Leneuve P, Cervera P, Perin L, Loudes C, Blaise A, Klein R, Epelbaum J, Le Bouc Y, Holzenberger M. PLoS Biol. 2008;6:e254.

    PubMed  PubMed Central  Google Scholar 

  20. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ. Science. 2009;326:140–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P. Proc Natl Acad Sci U S A. 2008;105:3438–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kojima T, Kamei H, Aizu T, Arai Y, Takayama M, Nakazawa S, Ebihara Y, Inagaki H, Masui Y, Gondo Y, Sakaki Y, Hirose N. Exp Gerontol. 2004;39:1595–8.

    CAS  PubMed  Google Scholar 

  23. Pawlikowska L, Hu D, Huntsman S, Sung A, Chu C, Chen J, Joyner AH, Schork NJ, Hsueh WC, Reiner AP, Psaty BM, Atzmon G, Barzilai N, Cummings SR, Browner WS, Kwok PY, Ziv E. Aging Cell. 2009;8:460–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD. Proc Natl Acad Sci U S A. 2008;105:13987–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA. Rejuvenation Res. 2009;12:95–104.

    CAS  PubMed  Google Scholar 

  26. Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A. Proc Natl Acad Sci U S A. 2009;106:2700–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Li Y, Wang WJ, Cao H, Lu J, Wu C, Hu FY, Guo J, Zhao L, Yang F, Zhang YX, Li W, Zheng GY, Cui H, Chen X, Zhu Z, He H, Dong B, Mo X, Zeng Y, Tian XL. Hum Mol Genet. 2009;18:4897–904.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lunetta KL, D'Agostino RB Sr, Karasik D, Benjamin EJ, Guo CY, Govindaraju R, Kiel DP, Kelly-Hayes M, Massaro JM, Pencina MJ, Seshadri S, Murabito JM. BMC Med Genet. 2007;8(Suppl 1):S13.

    PubMed  PubMed Central  Google Scholar 

  29. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. Nature. 1993;366:461–4.

    CAS  PubMed  Google Scholar 

  30. Honjoh S, Yamamoto T, Uno M, Nishida E. Nature. 2009;457:726–30.

    CAS  PubMed  Google Scholar 

  31. Clancy DJ, Gems D, Hafen E, Leevers SJ, Partridge L. Science. 2002;296:319.

    CAS  PubMed  Google Scholar 

  32. Grandison RC, Piper MD, Partridge L. Nature. 2009;462:1061–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Science. 2005;310:1193–6.

    CAS  PubMed  Google Scholar 

  34. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Curr Biol. 2004;14:885–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Nature. 2009;460:392–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Jia K, Chen D, Riddle DL. Development. 2004;131:3897–906.

    CAS  PubMed  Google Scholar 

  37. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F. Nature. 2003;426:620.

    CAS  PubMed  Google Scholar 

  38. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C. Aging Cell. 2007;6:95–110.

    CAS  PubMed  Google Scholar 

  39. Hamilton B, Dong Y, Shindo M, Liu W, Odell I, Ruvkun G, Lee SS. Genes Dev. 2005;19:1544–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Pan KZ, Palter JE, Rogers AN, Olsen A, Chen D, Lithgow GJ, Kapahi P. Aging Cell. 2007;6:111–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Syntichaki P, Troulinaki K, Tavernarakis N. Nature. 2007;445:922–6.

    CAS  PubMed  Google Scholar 

  42. Steffen KK, MacKay VL, Kerr EO, Tsuchiya M, Hu D, Fox LA, Dang N, Johnston ED, Oakes JA, Tchao BN, Pak DN, Fields S, Kennedy BK, Kaeberlein M. Cell. 2008;133:292–302.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C. PLoS Genet. 2008;4:e24.

    PubMed  PubMed Central  Google Scholar 

  44. Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. Cell Metab. 2010;11:35–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T. Autophagy. 2008;4:330–8.

    CAS  PubMed  Google Scholar 

  46. Apfeld J, O'Connor G, McDonagh T, DiStefano PS, Curtis R. Genes Dev. 2004;18:3004–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Yurova MV, Kovalenko IG, Poroshina TE, Semenchenko AV. Cell Cycle. 2008;7:2769–73.

    CAS  PubMed  Google Scholar 

  48. Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A. Curr Biol. 2007;17:1646–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Lakowski B, Hekimi S. Proc Natl Acad Sci U S A. 1998;95:13091–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Greer EL, Brunet A. Aging Cell. 2009;8:113–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Kaeberlein M, Powers RW 3rd. Ageing Res Rev. 2007;6:128–40.

    CAS  PubMed  Google Scholar 

  52. Dang W, Steffen KK, Perry R, Dorsey JA, Johnson FB, Shilatifard A, Kaeberlein M, Kennedy BK, Berger SL. Nature. 2009;459:802–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L. Cell. 2006;125:1165–77.

    CAS  PubMed  Google Scholar 

  54. Copeland JM, Cho J, Lo T Jr, Hur JH, Bahadorani S, Arabyan T, Rabie J, Soh J, Walker DW. Curr Biol. 2009;19:1591–8.

    CAS  PubMed  Google Scholar 

  55. Dell'agnello C, Leo S, Agostino A, Szabadkai G, Tiveron C, Zulian A, Prelle A, Roubertoux P, Rizzuto R, Zeviani M. Hum Mol Genet. 2007;16:431–44.

    CAS  PubMed  Google Scholar 

  56. Kayser EB, Sedensky MM, Morgan PG, Hoppel CL. J Biol Chem. 2004;279:54479–86.

    CAS  PubMed  Google Scholar 

  57. Lapointe J, Hekimi S. J Biol Chem. 2008;283:26217–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Cristina D, Cary M, Lunceford A, Clarke C, Kenyon C. PLoS Genet. 2009;5:e1000450.

    PubMed  PubMed Central  Google Scholar 

  59. Kirchman PA, Kim S, Lai CY, Jazwinski SM. Genetics. 1999;152:179–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Rea SL, Ventura N, Johnson TE. PLoS Biol. 2007;5:e259.

    PubMed  PubMed Central  Google Scholar 

  61. Atzmon G, Cho M, Cawthon RM, Budagov T, Katz M, Yang X, Siegel G, Bergman A, Huffman DM, Schechter CB, Wright WE, Shay JW, Barzilai N, Govindaraju DR, Suh Y. Proc Natl Acad Sci U S A. 2010;107(Suppl 1):1710–7.

    CAS  PubMed  Google Scholar 

  62. Chen JH, Hales CN, Ozanne SE. Nucleic Acids Res. 2007;35:7417–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Lenaz G. Biochim Biophys Acta. 1998;1366:53–67.

    CAS  PubMed  Google Scholar 

  64. Linnane AW, Marzuki S, Ozawa T, Tanaka M. Lancet. 1989;1:642–5.

    CAS  PubMed  Google Scholar 

  65. Toescu EC, Myronova N, Verkhratsky A. Cell Calcium. 2000;28:329–38.

    CAS  PubMed  Google Scholar 

  66. Harman D. J Gerontol. 1956;11:298–300.

    CAS  PubMed  Google Scholar 

  67. Harman D. J Am Geriatr Soc. 1972;20:145–7.

    CAS  PubMed  Google Scholar 

  68. Balaban RS, Nemoto S, Finkel T. Cell. 2005;120:483–95.

    CAS  PubMed  Google Scholar 

  69. Gough DR, Cotter TG. Cell Death Dis. 2011;2:e213.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Lemarie A, Huc L, Pazarentzos E, Mahul-Mellier AL, Grimm S. Cell Death Differ. 2011;18:338–49.

    CAS  PubMed  Google Scholar 

  71. Lambert AJ, Boysen HM, Buckingham JA, Yang T, Podlutsky A, Austad SN, Kunz TH, Buffenstein R, Brand MD. Aging Cell. 2007;6:607–18.

    CAS  PubMed  Google Scholar 

  72. Lu T, Finkel T. Exp Cell Res. 2008;314:1918–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Millis AJ, Hoyle M, McCue HM, Martini H. Exp Cell Res. 1992;201:373–9.

    CAS  PubMed  Google Scholar 

  74. Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T. Nature. 2007;445:661–5.

    CAS  PubMed  Google Scholar 

  75. Maier B, Gluba W, Bernier B, Turner T, Mohammad K, Guise T, Sutherland A, Thorner M, Scrable H. Genes Dev. 2004;18:306–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Kang MK, Kameta A, Shin KH, Baluda MA, Kim HR, Park NH. Exp Cell Res. 2003;287:272–81.

    CAS  PubMed  Google Scholar 

  77. Martins CP, Brown-Swigart L, Evan GI. Cell. 2006;127:1323–34.

    CAS  PubMed  Google Scholar 

  78. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Science. 1998;279:349–52.

    CAS  PubMed  Google Scholar 

  79. Aubert G, Lansdorp PM. Physiol Rev. 2008;88:557–79.

    CAS  PubMed  Google Scholar 

  80. Pinkston JM, Garigan D, Hansen M, Kenyon C. Science. 2006;313:971–5.

    CAS  PubMed  Google Scholar 

  81. Rufini A, Tucci P, Celardo I, Melino G. Oncogene. 2013;32:5129–43.

    CAS  PubMed  Google Scholar 

  82. Tomas-Loba A, Flores I, Fernandez-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borras C, Matheu A, Klatt P, Flores JM, Vina J, Serrano M, Blasco MA. Cell. 2008;135:609–22.

    CAS  PubMed  Google Scholar 

  83. Kon N, Zhong J, Kobayashi Y, Li M, Szabolcs M, Ludwig T, Canoll PD, Gu W. Cell Death Differ. 2011;18:1366–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Sah VP, Attardi LD, Mulligan GJ, Williams BO, Bronson RT, Jacks T. Nat Genet. 1995;10:175–80.

    CAS  PubMed  Google Scholar 

  85. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. Nat Rev Mol Cell Biol. 2011;12:259–65.

    CAS  PubMed  Google Scholar 

  86. Gottlieb E, Vousden KH. Cold Spring Harb Perspect Biol. 2010;2:a001040.

    PubMed  PubMed Central  Google Scholar 

  87. Begus-Nahrmann Y, Lechel A, Obenauf AC, Nalapareddy K, Peit E, Hoffmann E, Schlaudraff F, Liss B, Schirmacher P, Kestler H, Danenberg E, Barker N, Clevers H, Speicher MR, Rudolph KL. Nat Genet. 2009;41:1138–43.

    CAS  PubMed  Google Scholar 

  88. Feng Z, Lin M, Wu R. Genes Cancer. 2011;2:443–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Marcel V, Dichtel-Danjoy ML, Sagne C, Hafsi H, Ma D, Ortiz-Cuaran S, Olivier M, Hall J, Mollereau B, Hainaut P, Bourdon JC. Cell Death Differ. 2011;18:1815–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Liu D, Ou L, Clemenson JGD, Chao C, Lutske ME, Zambetti GP, Gage FH, Xu Y. Puma is required for p53-induced depletion of adult stem cells. Nat Cell Biol. 2010;12:993–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Pollina EA, Brunet A. Oncogene. 2011;30:3105–26.

    CAS  PubMed  Google Scholar 

  92. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A. Nature. 1992;356:215–21.

    CAS  PubMed  Google Scholar 

  93. Armata HL, Garlick DS, Sluss HK. Cancer Res. 2007;67:11696–703.

    CAS  PubMed  Google Scholar 

  94. Spinnler C, Hedstrom E, Li H, de Lange J, Nikulenkov F, Teunisse AF, Verlaan-de Vries M, Grinkevich V, Jochemsen AG, Selivanova G. Cell Death Differ. 2011;18:1736–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Matheu A, Maraver A, Klatt P, Flores I, Garcia-Cao I, Borras C, Flores JM, Vina J, Blasco MA, Serrano M. Nature. 2007;448:375–9.

    CAS  PubMed  Google Scholar 

  96. Matheu A, Maraver A, Serrano M. Cancer Res. 2008;68:6031–4.

    CAS  PubMed  Google Scholar 

  97. Thomas G. Biol Res. 2002;35:305–13.

    CAS  PubMed  Google Scholar 

  98. Inoki K, Zhu T, Guan KL. Cell. 2003;115:577–90.

    CAS  PubMed  Google Scholar 

  99. Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB. Cell. 2005;120:237–48.

    CAS  PubMed  Google Scholar 

  100. Feng Z, Zhang H, Levine AJ, Jin S. Proc Natl Acad Sci U S A. 2005;102:8204–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, Levine AJ. Cancer Res. 2007;67:3043–53.

    CAS  PubMed  Google Scholar 

  102. Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV. Proc Natl Acad Sci U S A. 2010;107:9660–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Lee JJ, Kim BC, Park MJ, Lee YS, Kim YN, Lee BL, Lee JS. Cell Death Differ. 2011;18:666–77.

    CAS  PubMed  Google Scholar 

  104. Aksoy O, Chicas A, Zeng T, Zhao Z, McCurrach M, Wang X, Lowe SW. Genes Dev. 2012;26:1546–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Carvajal LA, Hamard PJ, Tonnessen C, Manfredi JJ. Genes Dev. 2012;26:1533–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Di Stefano L, Jensen MR, Helin K. EMBO J. 2003;22:6289–98.

    PubMed  PubMed Central  Google Scholar 

  107. Logan N, Delavaine L, Graham A, Reilly C, Wilson J, Brummelkamp TR, Hijmans EM, Bernards R, La Thangue NB. Oncogene. 2004;23:5138–50.

    CAS  PubMed  Google Scholar 

  108. Klionsky DJ. Nat Rev Mol Cell Biol. 2007;8:931–7.

    CAS  PubMed  Google Scholar 

  109. Rubinsztein DC, Marino G, Kroemer G. Cell. 2011;146:682–95.

    CAS  PubMed  Google Scholar 

  110. Hofius D, Munch D, Bressendorff S, Mundy J, Petersen M. Cell Death Differ. 2011;18:1257–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Wu WK, Coffelt SB, Cho CH, Wang XJ, Lee CW, Chan FK, Yu J, Sung JJ. Oncogene. 2012;31:939–53.

    CAS  PubMed  Google Scholar 

  112. Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, Ocorr K, Ellisman MH, Bodmer R, Bier E, Karin M. Science. 2010;327:1223–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Matecic M, Smith DL, Pan X, Maqani N, Bekiranov S, Boeke JD, Smith JS. PLoS Genet. 2010;6:e1000921.

    PubMed  PubMed Central  Google Scholar 

  114. Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C, Liu LF. Autophagy. 2007;3:93–5.

    CAS  PubMed  Google Scholar 

  115. Minois N, Carmona-Gutierrez D, Bauer MA, Rockenfeller P, Eisenberg T, Brandhorst S, Sigrist SJ, Kroemer G, Madeo F. Cell Death Dis. 2012;3:e401.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Levine B, Kroemer G. Cell Death Differ. 2009;16:1–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L. Cell Metab. 2010;11:453–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Gao W, Shen Z, Shang L, Wang X. Cell Death Differ. 2011;18:1598–607.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Maiuri MC, Galluzzi L, Morselli E, Kepp O, Malik SA, Kroemer G. Curr Opin Cell Biol. 2010;22:181–5.

    CAS  PubMed  Google Scholar 

  120. Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D'Amelio M, Criollo A, Morselli E, Zhu C, Harper F, Nannmark U, Samara C, Pinton P, Vicencio JM, Carnuccio R, Moll UM, Madeo F, Paterlini-Brechot P, Rizzuto R, Szabadkai G, Pierron G, Blomgren K, Tavernarakis N, Codogno P, Cecconi F, Kroemer G. Nat Cell Biol. 2008;10:676–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Liang C. Cell Death Differ. 2010;17:1807–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Feng Z, Hu W, Teresky AK, Hernando E, Cordon-Cardo C, Levine AJ. Proc Natl Acad Sci U S A. 2007;104:16633–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Salminen A, Kaarniranta K. Trends Mol Med. 2009;15:217–24.

    CAS  PubMed  Google Scholar 

  124. Crighton D, Wilkinson S, O'Prey J, Syed N, Smith P, Harrison PR, Gasco M, Garrone O, Crook T, Ryan KM. Cell. 2006;126:121–34.

    CAS  PubMed  Google Scholar 

  125. Kang MY, Kim HB, Piao C, Lee KH, Hyun JW, Chang IY, You HJ. Cell Death Differ. 2013;20:117–29.

    CAS  PubMed  Google Scholar 

  126. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. Nature. 1997;389:300–5.

    CAS  PubMed  Google Scholar 

  127. Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Science. 2004;304:596–600.

    CAS  PubMed  Google Scholar 

  128. Hussain SP, Amstad P, He P, Robles A, Lupold S, Kaneko I, Ichimiya M, Sengupta S, Mechanic L, Okamura S, Hofseth LJ, Moake M, Nagashima M, Forrester KS, Harris CC. Cancer Res. 2004;64:2350–6.

    CAS  PubMed  Google Scholar 

  129. Tan M, Li S, Swaroop M, Guan K, Oberley LW, Sun Y. J Biol Chem. 1999;274:12061–6.

    CAS  PubMed  Google Scholar 

  130. Olovnikov IA, Kravchenko JE, Chumakov PM. Semin Cancer Biol. 2009;19:32–41.

    CAS  PubMed  Google Scholar 

  131. Johnson TM, Yu ZX, Ferrans VJ, Lowenstein RA, Finkel T. Proc Natl Acad Sci U S A. 1996;93:11848–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Macip S, Igarashi M, Berggren P, Yu J, Lee SW, Aaronson SA. Mol Cell Biol. 2003;23:8576–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Dumble M, Moore L, Chambers SM, Geiger H, Van Zant G, Goodell MA, Donehower LA. Blood. 2007;109:1736–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Cao L, Li W, Kim S, Brodie SG, Deng CX. Genes Dev. 2003;17:201–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Varela I, Cadinanos J, Pendas AM, Gutierrez-Fernandez A, Folgueras AR, Sanchez LM, Zhou Z, Rodriguez FJ, Stewart CL, Vega JA, Tryggvason K, Freije JM, Lopez-Otin C. Nature. 2005;437:564–8.

    CAS  PubMed  Google Scholar 

  136. Sherr CJ. Nat Rev Cancer. 2006;6:663–73.

    CAS  PubMed  Google Scholar 

  137. Yoon KA, Nakamura Y, Arakawa H. J Hum Genet. 2004;49:134–40.

    CAS  PubMed  Google Scholar 

  138. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. Cell. 2006;126:107–20.

    CAS  PubMed  Google Scholar 

  139. Bensaad K, Vousden KH. Trends Cell Biol. 2007;17:286–91.

    CAS  PubMed  Google Scholar 

  140. Donald SP, Sun XY, Hu CA, Yu J, Mei JM, Valle D, Phang JM. Cancer Res. 2001;61:1810–5.

    CAS  PubMed  Google Scholar 

  141. Liu Z, Lu H, Shi H, Du Y, Yu J, Gu S, Chen X, Liu KJ, Hu CA. Cancer Res. 2005;65:1647–54.

    CAS  PubMed  Google Scholar 

  142. Drane P, Bravard A, Bouvard V, May E. Oncogene. 2001;20:430–9.

    CAS  PubMed  Google Scholar 

  143. Faraonio R, Vergara P, Di Marzo D, Pierantoni MG, Napolitano M, Russo T, Cimino F. J Biol Chem. 2006;281:39776–84.

    CAS  PubMed  Google Scholar 

  144. Pani G, Bedogni B, Anzevino R, Colavitti R, Palazzotti B, Borrello S, Galeotti T. Cancer Res. 2000;60:4654–60.

    CAS  PubMed  Google Scholar 

  145. Liu D, Xu Y. Antioxid Redox Signal. 2011;15:1669–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Finkel T, Serrano M, Blasco MA. Nature. 2007;448:767–74.

    CAS  PubMed  Google Scholar 

  147. Papazoglu C, Mills AA. J Pathol. 2007;211:124–33.

    CAS  PubMed  Google Scholar 

  148. de Magalhaes JP, Curado J, Church GM. Bioinformatics. 2009;25:875–81.

    PubMed  PubMed Central  Google Scholar 

  149. Zentella A, Manogue K, Cerami A. Cytokine. 1993;5:436–47.

    CAS  PubMed  Google Scholar 

  150. Benigni F, Atsumi T, Calandra T, Metz C, Echtenacher B, Peng T, Bucala R. J Clin Invest. 2000;106:1291–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Bauer DE, Harris MH, Plas DR, Lum JJ, Hammerman PS, Rathmell JC, Riley JL, Thompson CB. FASEB J. 2004;18:1303–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Atsumi T, Cho YR, Leng L, McDonald C, Yu T, Danton C, Hong EG, Mitchell RA, Metz C, Niwa H, Takeuchi J, Onodera S, Umino T, Yoshioka N, Koike T, Kim JK, Bucala R. J Immunol. 2007;179:5399–406.

    CAS  PubMed  Google Scholar 

  153. Jung H, Seong HA, Ha H. J Biol Chem. 2008;283:20383–96.

    CAS  PubMed  Google Scholar 

  154. Helenius M, Hanninen M, Lehtinen SK, Salminen A. Biochem J. 1996;318 (. Pt 2:603–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Spencer NF, Poynter ME, Im SY, Daynes RA. Int Immunol. 1997;9:1581–8.

    CAS  PubMed  Google Scholar 

  156. Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY. Genes Dev. 2007;21:3244–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF. Cell. 2009;136:62–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Renner F, Schmitz ML. Trends Biochem Sci. 2009;34:128–35.

    CAS  PubMed  Google Scholar 

  159. Salminen A, Ojala J, Huuskonen J, Kauppinen A, Suuronen T, Kaarniranta K. Cell Mol Life Sci. 2008;65:1049–58.

    CAS  PubMed  Google Scholar 

  160. Longo VD, Kennedy BK. Cell. 2006;126:257–68.

    CAS  PubMed  Google Scholar 

  161. Gloire G, Legrand-Poels S, Piette J. Biochem Pharmacol. 2006;72:1493–505.

    CAS  PubMed  Google Scholar 

  162. Ota H, Akishita M, Eto M, Iijima K, Kaneki M, Ouchi Y. J Mol Cell Cardiol. 2007;43:571–9.

    CAS  PubMed  Google Scholar 

  163. Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP, Pelicci PG. Nature. 2000;406:207–10.

    CAS  PubMed  Google Scholar 

  164. Dixit D, Sharma V, Ghosh S, Mehta VS, Sen E. Cell Death Dis. 2012;3:e271.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Deng CX. Int J Biol Sci. 2009;5:147–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W. Cell. 2001;107:137–48.

    CAS  PubMed  Google Scholar 

  167. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA. Cell. 2001;107:149–59.

    CAS  PubMed  Google Scholar 

  168. Campagna M, Herranz D, Garcia MA, Marcos-Villar L, Gonzalez-Santamaria J, Gallego P, Gutierrez S, Collado M, Serrano M, Esteban M, Rivas C. Cell Death Differ. 2011;18:72–9.

    CAS  PubMed  Google Scholar 

  169. Feldman JL, Dittenhafer-Reed KE, Denu JM. J Biol Chem. 2012;287:42419–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Houtkooper RH, Pirinen E, Auwerx J. Nat Rev Mol Cell Biol. 2012;13:225–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Brooks CL, Gu W. Nat Rev Cancer. 2009;9:123–8.

    CAS  PubMed  Google Scholar 

  172. Li L, Wang L, Wang Z, Ho Y, McDonald T, Holyoake TL, Chen W, Bhatia R. Cancer Cell. 2012;21:266–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Krummel KA, Lee CJ, Toledo F, Wahl GM. Proc Natl Acad Sci U S A. 2005;102:10188–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Dotsch V, Bernassola F, Coutandin D, Candi E, Melino G. p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol. 2010;2:a004887.

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, McKeon F. Nature. 1999;398:714–8.

    CAS  PubMed  Google Scholar 

  176. Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A. Nature. 1999;398:708–13.

    CAS  PubMed  Google Scholar 

  177. Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D, Yang A, McKeon F, Jacks T. Cancer Cell. 2005;7:363–73.

    CAS  PubMed  Google Scholar 

  178. Keyes WM, Wu Y, Vogel H, Guo X, Lowe SW, Mills AA. Genes Dev. 2005;19:1986–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Salomoni P, Dvorkina M, Michod D. Cell Death Dis. 2012;3:e247.

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Peche LY, Scolz M, Ladelfa MF, Monte M, Schneider C. Cell Death Differ. 2012;19:926–36.

    CAS  PubMed  Google Scholar 

  181. Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER. Cell Stem Cell. 2009;5:64–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Paris M, Rouleau M, Puceat M, Aberdam D. Cell Death Differ. 2012;19:186–93.

    CAS  PubMed  Google Scholar 

  183. Guo X, Keyes WM, Papazoglu C, Zuber J, Li W, Lowe SW, Vogel H, Mills AA. Nat Cell Biol. 2009;11:1451–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Zaika A, Irwin M, Sansome C, Moll UM. J Biol Chem. 2001;276:11310–6.

    CAS  PubMed  Google Scholar 

  185. Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung CC, Khan F, Itie-Youten A, Wakeham A, Tsao MS, Iovanna JL, Squire J, Jurisica I, Kaplan D, Melino G, Jurisicova A, Mak TW. Genes Dev. 2008;22:2677–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Rufini A, Niklison-Chirou MV, Inoue S, Tomasini R, Harris IS, Marino A, Federici M, Dinsdale D, Knight RA, Melino G, Mak TW. Genes Dev. 2012;26:2009–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Feng Z, Hu W, Rajagopal G, Levine AJ. Cell Cycle. 2008;7:842–7.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tapas Mukhopadhyay .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dogra, N., Mukhopadhyay, T. (2020). p53 and Aging. In: Rath, P. (eds) Models, Molecules and Mechanisms in Biogerontology. Springer, Singapore. https://doi.org/10.1007/978-981-32-9005-1_5

Download citation

Publish with us

Policies and ethics