Skip to main content
SpringerLink
Log in

Mouse Models of Accelerated Cellular Senescence

  • Protocol
  • First Online:
Cellular Senescence

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1896))

Abstract

Senescent cells accumulate in multiple tissues as virtually all vertebrate organisms age. Senescence is a highly conserved response to many forms of cellular stress intended to block the propagation of damaged cells. Senescent cells have been demonstrated to play a causal role in aging via their senescence-associated secretory phenotype and by impeding tissue regeneration. Depletion of senescent cells either through genetic or pharmacologic methods has been demonstrated to extend murine lifespan and delay the onset of age-related diseases. Measuring the burden and location of senescent cells in vivo remains challenging, as there is no marker unique to senescent cells. Here, we describe multiple methods to detect the presence and extent of cellular senescence in preclinical models, with a special emphasis on murine models of accelerated aging that exhibit a more rapid onset of cellular senescence.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
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. Sharpless NE, Sherr CJ (2015) Forging a signature of in vivo senescence. Nat Rev Cancer 15(7):397–408. https://doi.org/10.1038/nrc3960

    Article  CAS  PubMed  Google Scholar 

  2. Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685–705. https://doi.org/10.1146/annurev-physiol-030212-183653

    Article  CAS  PubMed  Google Scholar 

  3. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garre M, Nuciforo PG, Bensimon A, Maestro R, Pelicci PG, d'Adda di Fagagna F (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444(7119):638–642. https://doi.org/10.1038/nature05327

    Article  CAS  PubMed  Google Scholar 

  4. Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, Takaoka M, Nakagawa H, Tort F, Fugger K, Johansson F, Sehested M, Andersen CL, Dyrskjot L, Orntoft T, Lukas J, Kittas C, Helleday T, Halazonetis TD, Bartek J, Gorgoulis VG (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444(7119):633–637. https://doi.org/10.1038/nature05268

    Article  CAS  PubMed  Google Scholar 

  5. Campisi J, d'Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8(9):729–740. https://doi.org/10.1038/nrm2233

    Article  CAS  PubMed  Google Scholar 

  6. Guarente L, Partridge L, Wallace DC (2008) Molecular biology of aging. Cold Spring Harbor monograph series, vol 51. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  7. van Deursen JM (2014) The role of senescent cells in ageing. Nature 509(7501):439–446. https://doi.org/10.1038/nature13193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Munoz-Espin D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15(7):482–496. https://doi.org/10.1038/nrm3823

    Article  CAS  PubMed  Google Scholar 

  9. Coppe JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5:99–118. https://doi.org/10.1146/annurev-pathol-121808-102144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123(3):966–972. https://doi.org/10.1172/JCI64098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443(7110):453–457. https://doi.org/10.1038/nature05092

    Article  CAS  PubMed  Google Scholar 

  12. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443(7110):421–426. https://doi.org/10.1038/nature05159

    Article  CAS  PubMed  Google Scholar 

  13. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE, Morrison SJ (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443(7110):448–452. https://doi.org/10.1038/nature05091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114(9):1299–1307. https://doi.org/10.1172/JCI22475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE (2009) Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell 8(4):439–448. https://doi.org/10.1111/j.1474-9726.2009.00489.x

    Article  CAS  PubMed  Google Scholar 

  16. Ressler S, Bartkova J, Niederegger H, Bartek J, Scharffetter-Kochanek K, Jansen-Durr P, Wlaschek M (2006) p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 5(5):379–389. https://doi.org/10.1111/j.1474-9726.2006.00231.x

    Article  CAS  PubMed  Google Scholar 

  17. Waaijer ME, Parish WE, Strongitharm BH, van Heemst D, Slagboom PE, de Craen AJ, Sedivy JM, Westendorp RG, Gunn DA, Maier AB (2012) The number of p16INK4a positive cells in human skin reflects biological age. Aging Cell 11(4):722–725. https://doi.org/10.1111/j.1474-9726.2012.00837.x

    Article  CAS  PubMed  Google Scholar 

  18. Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311(5765):1257. https://doi.org/10.1126/science.1122446

    Article  CAS  PubMed  Google Scholar 

  19. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM (2016) Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530(7589):184–189. https://doi.org/10.1038/nature16932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236. https://doi.org/10.1038/nature10600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Miller JK (2001) Escaping senescence: demographic data from the three-toed box turtle (Terrapene carolina triunguis). Exp Gerontol 36(4–6):829–832

    Article  CAS  PubMed  Google Scholar 

  22. Finch CE (2009) Update on slow aging and negligible senescence--a mini-review. Gerontology 55(3):307–313. https://doi.org/10.1159/000215589

    Article  PubMed  Google Scholar 

  23. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL (2015) The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14(4):644–658. https://doi.org/10.1111/acel.12344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fuhrmann-Stroissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, Grassi D, Gregg SQ, Stripay JL, Dorronsoro A, Corbo L, Tang P, Bukata C, Ring N, Giacca M, Li X, Tchkonia T, Kirkland JL, Niedernhofer LJ, Robbins PD (2017) Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun 8(1):422. https://doi.org/10.1038/s41467-017-00314-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, Krager K, Ponnappan U, Hauer-Jensen M, Meng A, Zhou D (2016) Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 22(1):78–83. https://doi.org/10.1038/nm.4010

    Article  CAS  PubMed  Google Scholar 

  26. Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL, Negley BA, Sfeir JG, Ogrodnik MB, Hachfeld CM, LeBrasseur NK, Drake MT, Pignolo RJ, Pirtskhalava T, Tchkonia T, Oursler MJ, Kirkland JL, Khosla S (2017) Targeting cellular senescence prevents age-related bone loss in mice. Nat Med 23(9):1072–1079. https://doi.org/10.1038/nm.4385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lehmann M, Korfei M, Mutze K, Klee S, Skronska-Wasek W, Alsafadi HN, Ota C, Costa R, Schiller HB, Lindner M, Wagner DE, Gunther A, Konigshoff M (2017) Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo. Eur Respir J 50(2). https://doi.org/10.1183/13993003.02367-2016

  28. Ogrodnik M, Miwa S, Tchkonia T, Tiniakos D, Wilson CL, Lahat A, Day CP, Burt A, Palmer A, Anstee QM, Grellscheid SN, Hoeijmakers JHJ, Barnhoorn S, Mann DA, Bird TG, Vermeij WP, Kirkland JL, Passos JF, von Zglinicki T, Jurk D (2017) Cellular senescence drives age-dependent hepatic steatosis. Nat Commun 8:15691. https://doi.org/10.1038/ncomms15691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Roos CM, Zhang B, Palmer AK, Ogrodnik MB, Pirtskhalava T, Thalji NM, Hagler M, Jurk D, Smith LA, Casaclang-Verzosa G, Zhu Y, Schafer MJ, Tchkonia T, Kirkland JL, Miller JD (2016) Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15(5):973–977. https://doi.org/10.1111/acel.12458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ, Oberg AL, Birch J, Salmonowicz H, Zhu Y, Mazula DL, Brooks RW, Fuhrmann-Stroissnigg H, Pirtskhalava T, Prakash YS, Tchkonia T, Robbins PD, Aubry MC, Passos JF, Kirkland JL, Tschumperlin DJ, Kita H, LeBrasseur NK (2017) Cellular senescence mediates fibrotic pulmonary disease. Nat Commun 8:14532. https://doi.org/10.1038/ncomms14532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IWF, Houtsmuller AB, Pothof J, de Bruin RWF, Madl T, Hoeijmakers JHJ, Campisi J, de Keizer PLJ (2017) Targeted apoptosis of senescent cells restores tissue homeostasis in response to Chemotoxicity and aging. Cell 169(1):132–147 e116. https://doi.org/10.1016/j.cell.2017.02.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM (2016) Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 354(6311):472–477. https://doi.org/10.1126/science.aaf6659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moncsek A, Al-Suraih MS, Trussoni CE, O'Hara SP, Splinter PL, Zuber C, Patsenker E, Valli PV, Fingas CD, Weber A, Zhu Y, Tchkonia T, Kirkland JL, Gores GJ, Mullhaupt B, LaRusso NF, Mertens JC (2018) Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2(−/−) ) mice. Hepatology 67(1):247–259. https://doi.org/10.1002/hep.29464

    Article  CAS  PubMed  Google Scholar 

  34. Yosef R, Pilpel N, Tokarsky-Amiel R, Biran A, Ovadya Y, Cohen S, Vadai E, Dassa L, Shahar E, Condiotti R, Ben-Porath I, Krizhanovsky V (2016) Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nat Commun 7:11190. https://doi.org/10.1038/ncomms11190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jeon OH, Kim C, Laberge RM, Demaria M, Rathod S, Vasserot AP, Chung JW, Kim DH, Poon Y, David N, Baker DJ, van Deursen JM, Campisi J, Elisseeff JH (2017) Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med 23(6):775–781. https://doi.org/10.1038/nm.4324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, Pirtskhalava T, Giorgadze N, Johnson KO, Giles CB, Wren JD, Niedernhofer LJ, Robbins PD, Kirkland JL (2015) Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15(3):428–435. https://doi.org/10.1111/acel.12445

    Article  CAS  Google Scholar 

  37. Andressoo JO, Mitchell JR, de Wit J, Hoogstraten D, Volker M, Toussaint W, Speksnijder E, Beems RB, van Steeg H, Jans J, de Zeeuw CI, Jaspers NG, Raams A, Lehmann AR, Vermeulen W, Hoeijmakers JH, van der Horst GT (2006) An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria. Cancer Cell 10(2):121–132. https://doi.org/10.1016/j.ccr.2006.05.027

    Article  CAS  PubMed  Google Scholar 

  38. Chiche A, Le Roux I, von Joest M, Sakai H, Aguin SB, Cazin C, Salam R, Fiette L, Alegria O, Flamant P, Tajbakhsh S, Li H (2017) Injury-induced senescence enables in vivo reprogramming in skeletal muscle. Cell Stem Cell 20(3):407–414 e404. https://doi.org/10.1016/j.stem.2016.11.020

    Article  CAS  PubMed  Google Scholar 

  39. Maejima Y, Adachi S, Ito H, Hirao K, Isobe M (2008) Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage. Aging Cell 7(2):125–136. https://doi.org/10.1111/j.1474-9726.2007.00358.x

    Article  CAS  PubMed  Google Scholar 

  40. Jurk D, Wang C, Miwa S, Maddick M, Korolchuk V, Tsolou A, Gonos ES, Thrasivoulou C, Saffrey MJ, Cameron K, von Zglinicki T (2012) Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 11(6):996–1004. https://doi.org/10.1111/j.1474-9726.2012.00870.x

    Article  CAS  PubMed  Google Scholar 

  41. Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J (2003) Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 22(16):4212–4222. https://doi.org/10.1093/emboj/cdg417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Munoz-Espin D, Canamero M, Maraver A, Gomez-Lopez G, Contreras J, Murillo-Cuesta S, Rodriguez-Baeza A, Varela-Nieto I, Ruberte J, Collado M, Serrano M (2013) Programmed cell senescence during mammalian embryonic development. Cell 155(5):1104–1118. https://doi.org/10.1016/j.cell.2013.10.019

    Article  CAS  PubMed  Google Scholar 

  43. Burd CE, Sorrentino JA, Clark KS, Darr DB, Krishnamurthy J, Deal AM, Bardeesy N, Castrillon DH, Beach DH, Sharpless NE (2013) Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model. Cell 152(1–2):340–351. https://doi.org/10.1016/j.cell.2012.12.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gadd M, Pisc C, Branda J, Ionescu-Tiba V, Nikolic Z, Yang C, Wang T, Shackleford GM, Cardiff RD, Schmidt EV (2001) Regulation of cyclin D1 and p16(INK4A) is critical for growth arrest during mammary involution. Cancer Res 61(24):8811–8819

    CAS  PubMed  Google Scholar 

  45. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, Laberge RM, Vijg J, Van Steeg H, Dolle ME, Hoeijmakers JH, de Bruin A, Hara E, Campisi J (2014) An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell 31(6):722–733. https://doi.org/10.1016/j.devcel.2014.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Palmer AK, Tchkonia T, LeBrasseur NK, Chini EN, Xu M, Kirkland JL (2015) Cellular senescence in type 2 diabetes: a therapeutic opportunity. Diabetes 64(7):2289–2298. https://doi.org/10.2337/db14-1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Harkema L, Youssef SA, de Bruin A (2016) Pathology of mouse models of accelerated aging. Vet Pathol 53(2):366–389. https://doi.org/10.1177/0300985815625169

    Article  CAS  PubMed  Google Scholar 

  48. Gurkar AU, Niedernhofer LJ (2015) Comparison of mice with accelerated aging caused by distinct mechanisms. Exp Gerontol 68:43–50. https://doi.org/10.1016/j.exger.2015.01.045

    Article  PubMed  PubMed Central  Google Scholar 

  49. Burtner CR, Kennedy BK (2010) Progeria syndromes and ageing: what is the connection? Nat Rev Mol Cell Biol 11(8):567–578. https://doi.org/10.1038/nrm2944

    Article  CAS  PubMed  Google Scholar 

  50. Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444(7122):1038–1043. https://doi.org/10.1038/nature05456

    Article  CAS  PubMed  Google Scholar 

  51. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300

    Article  CAS  PubMed  Google Scholar 

  52. Zhang Y, Unnikrishnan A, Deepa SS, Liu Y, Li Y, Ikeno Y, Sosnowska D, Van Remmen H, Richardson A (2017) A new role for oxidative stress in aging: the accelerated aging phenotype in Sod1(−/)(−) mice is correlated to increased cellular senescence. Redox Biol 11:30–37. https://doi.org/10.1016/j.redox.2016.10.014

    Article  CAS  PubMed  Google Scholar 

  53. Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A (2009) Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790(10):1005–1014. https://doi.org/10.1016/j.bbagen.2009.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Jacob KD, Noren Hooten N, Trzeciak AR, Evans MK (2013) Markers of oxidant stress that are clinically relevant in aging and age-related disease. Mech Ageing Dev 134(3–4):139–157. https://doi.org/10.1016/j.mad.2013.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Wang J, Clauson CL, Robbins PD, Niedernhofer LJ, Wang Y (2012) The oxidative DNA lesions 8,5′-cyclopurines accumulate with aging in a tissue-specific manner. Aging Cell 11(4):714–716. https://doi.org/10.1111/j.1474-9726.2012.00828.x

    Article  CAS  PubMed  Google Scholar 

  56. Maher P (2005) The effects of stress and aging on glutathione metabolism. Ageing Res Rev 4(2):288–314. https://doi.org/10.1016/j.arr.2005.02.005

    Article  CAS  PubMed  Google Scholar 

  57. Zhang H, Davies KJA, Forman HJ (2015) Oxidative stress response and Nrf2 signaling in aging. Free Radic Biol Med 88(Pt B):314–336. https://doi.org/10.1016/j.freeradbiomed.2015.05.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhang Y, Ikeno Y, Bokov A, Gelfond J, Jaramillo C, Zhang HM, Liu Y, Qi W, Hubbard G, Richardson A, Van Remmen H (2013) Dietary restriction attenuates the accelerated aging phenotype of Sod1(−/−) mice. Free Radic Biol Med 60:300–306. https://doi.org/10.1016/j.freeradbiomed.2013.02.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911. https://doi.org/10.1126/science.1106653

    Article  CAS  PubMed  Google Scholar 

  60. Guo Y, Kim C, Ahmad S, Zhang J, Mao Y (2012) CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint. J Cell Biol 198(2):205–217. https://doi.org/10.1083/jcb.201202152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Baker DJ, Dawlaty MM, Wijshake T, Jeganathan KB, Malureanu L, van Ree JH, Crespo-Diaz R, Reyes S, Seaburg L, Shapiro V, Behfar A, Terzic A, van de Sluis B, van Deursen JM (2013) Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nat Cell Biol 15(1):96–102. https://doi.org/10.1038/ncb2643

    Article  CAS  PubMed  Google Scholar 

  62. Weaver RL, Limzerwala JF, Naylor RM, Jeganathan KB, Baker DJ, van Deursen JM (2016) BubR1 alterations that reinforce mitotic surveillance act against aneuploidy and cancer. Elife 5. https://doi.org/10.7554/eLife.16620

  63. Baker DJ, Jeganathan KB, Cameron JD, Thompson M, Juneja S, Kopecka A, Kumar R, Jenkins RB, de Groen PC, Roche P, van Deursen JM (2004) BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat Genet 36(7):744–749. https://doi.org/10.1038/ng1382

    Article  CAS  PubMed  Google Scholar 

  64. Hartman TK, Wengenack TM, Poduslo JF, van Deursen JM (2007) Mutant mice with small amounts of BubR1 display accelerated age-related gliosis. Neurobiol Aging 28(6):921–927. https://doi.org/10.1016/j.neurobiolaging.2006.05.012

    Article  CAS  PubMed  Google Scholar 

  65. Matsumoto T, Baker DJ, d'Uscio LV, Mozammel G, Katusic ZS, van Deursen JM (2007) Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke 38(3):1050–1056. https://doi.org/10.1161/01.STR.0000257967.86132.01

    Article  CAS  PubMed  Google Scholar 

  66. Baker DJ, Perez-Terzic C, Jin F, Pitel KS, Niederlander NJ, Jeganathan K, Yamada S, Reyes S, Rowe L, Hiddinga HJ, Eberhardt NL, Terzic A, van Deursen JM (2008) Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat Cell Biol 10(7):825–836. https://doi.org/10.1038/ncb1744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Baker DJ, Weaver RL, van Deursen JM (2013) p21 both attenuates and drives senescence and aging in BubR1 progeroid mice. Cell Rep 3(4):1164–1174. https://doi.org/10.1016/j.celrep.2013.03.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kudlow BA, Kennedy BK, Monnat RJ Jr (2007) Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol 8(5):394–404. https://doi.org/10.1038/nrm2161

    Article  CAS  PubMed  Google Scholar 

  69. Hennekam RC (2006) Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 140(23):2603–2624. https://doi.org/10.1002/ajmg.a.31346

    Article  CAS  PubMed  Google Scholar 

  70. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS (2003) Recurrent de novo point mutations in Lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423(6937):293–298. https://doi.org/10.1038/nature01629

    Article  CAS  PubMed  Google Scholar 

  71. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Levy N (2003) Lamin a truncation in Hutchinson-Gilford progeria. Science 300(5628):2055. https://doi.org/10.1126/science.1084125

    Article  PubMed  Google Scholar 

  72. Cao H, Hegele RA (2003) LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet 48(5):271–274. https://doi.org/10.1007/s10038-003-0025-3

    Article  CAS  PubMed  Google Scholar 

  73. Moulson CL, Go G, Gardner JM, van der Wal AC, Smitt JH, van Hagen JM, Miner JH (2005) Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy. J Invest Dermatol 125(5):913–919. https://doi.org/10.1111/j.0022-202X.2005.23846.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL (2003) A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423(6937):298–301. https://doi.org/10.1038/nature01631

    Article  CAS  PubMed  Google Scholar 

  75. Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima K, Stewart CL, Burke B (1999) Loss of A-type Lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147(5):913–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Frock RL, Kudlow BA, Evans AM, Jameson SA, Hauschka SD, Kennedy BK (2006) Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev 20(4):486–500. https://doi.org/10.1101/gad.1364906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Varga R, Eriksson M, Erdos MR, Olive M, Harten I, Kolodgie F, Capell BC, Cheng J, Faddah D, Perkins S, Avallone H, San H, Qu X, Ganesh S, Gordon LB, Virmani R, Wight TN, Nabel EG, Collins FS (2006) Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 103(9):3250–3255. https://doi.org/10.1073/pnas.0600012103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Yang SH, Bergo MO, Toth JI, Qiao X, Hu Y, Sandoval S, Meta M, Bendale P, Gelb MH, Young SG, Fong LG (2005) Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc Natl Acad Sci U S A 102(29):10291–10296. https://doi.org/10.1073/pnas.0504641102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Fong LG, Frost D, Meta M, Qiao X, Yang SH, Coffinier C, Young SG (2006) A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 311(5767):1621–1623. https://doi.org/10.1126/science.1124875

    Article  CAS  PubMed  Google Scholar 

  80. Pendas AM, Zhou Z, Cadinanos J, Freije JM, Wang J, Hultenby K, Astudillo A, Wernerson A, Rodriguez F, Tryggvason K, Lopez-Otin C (2002) Defective prelamin a processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nat Genet 31(1):94–99. https://doi.org/10.1038/ng871

    Article  CAS  PubMed  Google Scholar 

  81. Benson EK, Lee SW, Aaronson SA (2010) Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence. J Cell Sci 123(Pt 15):2605–2612. https://doi.org/10.1242/jcs.067306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wheaton K, Campuzano D, Ma W, Sheinis M, Ho B, Brown GW, Benchimol S (2017) Progerin-induced replication stress facilitates premature senescence in Hutchinson-Gilford progeria syndrome. Mol Cell Biol 37(14). https://doi.org/10.1128/MCB.00659-16

  83. Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z (2013) Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun 4:1868. https://doi.org/10.1038/ncomms2885

    Article  CAS  PubMed  Google Scholar 

  84. Manandhar M, Boulware KS, Wood RD (2015) The ERCC1 and ERCC4 (XPF) genes and gene products. Gene 569(2):153–161. https://doi.org/10.1016/j.gene.2015.06.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Weeda G, Donker I, de Wit J, Morreau H, Janssens R, Vissers CJ, Nigg A, van Steeg H, Bootsma D, Hoeijmakers JH (1997) Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr Biol 7(6):427–439

    Article  CAS  PubMed  Google Scholar 

  86. Tian M, Shinkura R, Shinkura N, Alt FW (2004) Growth retardation, early death, and DNA repair defects in mice deficient for the nucleotide excision repair enzyme XPF. Mol Cell Biol 24(3):1200–1205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. McWhir J, Selfridge J, Harrison DJ, Squires S, Melton DW (1993) Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nat Genet 5(3):217–224. https://doi.org/10.1038/ng1193-217

    Article  CAS  PubMed  Google Scholar 

  88. Selfridge J, Hsia KT, Redhead NJ, Melton DW (2001) Correction of liver dysfunction in DNA repair-deficient mice with an ERCC1 transgene. Nucleic Acids Res 29(22):4541–4550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Dolle ME, Kuiper RV, Roodbergen M, Robinson J, de Vlugt S, Wijnhoven SW, Beems RB, de la Fonteyne L, de With P, van der Pluijm I, Niedernhofer LJ, Hasty P, Vijg J, Hoeijmakers JH, van Steeg H (2011) Broad segmental progeroid changes in short-lived Ercc1−/Δ7 mice. Pathobiol Aging Age Relat Dis 1. https://doi.org/10.3402/pba.v1i0.7219

  90. Gregg SQ, Robinson AR, Niedernhofer LJ (2011) Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA Repair 10(7):781–791. https://doi.org/10.1016/j.dnarep.2011.04.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Goss JR, Stolz DB, Robinson AR, Zhang M, Arbujas N, Robbins PD, Glorioso JC, Niedernhofer LJ (2011) Premature aging-related peripheral neuropathy in a mouse model of progeria. Mech Ageing Dev 132(8–9):437–442. https://doi.org/10.1016/j.mad.2011.04.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Spoor M, Nagtegaal AP, Ridwan Y, Borgesius NZ, van Alphen B, van der Pluijm I, Hoeijmakers JH, Frens MA, Borst JG (2012) Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1(delta/−) mouse. Mech Ageing Dev 133(2–3):59–67. https://doi.org/10.1016/j.mad.2011.12.003

    Article  CAS  PubMed  Google Scholar 

  93. de Waard MC, van der Pluijm I, Zuiderveen Borgesius N, Comley LH, Haasdijk ED, Rijksen Y, Ridwan Y, Zondag G, Hoeijmakers JH, Elgersma Y, Gillingwater TH, Jaarsma D (2010) Age-related motor neuron degeneration in DNA repair-deficient Ercc1 mice. Acta Neuropathol 120(4):461–475. https://doi.org/10.1007/s00401-010-0715-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Vo N, Seo HY, Robinson A, Sowa G, Bentley D, Taylor L, Studer R, Usas A, Huard J, Alber S, Watkins SC, Lee J, Coehlo P, Wang D, Loppini M, Robbins PD, Niedernhofer LJ, Kang J (2010) Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res 28(12):1600–1607. https://doi.org/10.1002/jor.21153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Chen Q, Liu K, Robinson AR, Clauson CL, Blair HC, Robbins PD, Niedernhofer LJ, Ouyang H (2013) DNA damage drives accelerated bone aging via an NF-kappaB-dependent mechanism. J Bone Miner Res 28(5):1214–1228. https://doi.org/10.1002/jbmr.1851

    Article  CAS  PubMed  Google Scholar 

  96. Roh DS, Du Y, Gabriele ML, Robinson AR, Niedernhofer LJ, Funderburgh JL (2013) Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice. Aging Cell 12(6):1122–1131. https://doi.org/10.1111/acel.12143

    Article  CAS  PubMed  Google Scholar 

  97. Robinson AR, Yousefzadeh MJ, Rozgaja TA, Wang J, Li X, Tilstra JS, Feldman CH, Gregg SQ, Johnson CH, Skoda EM, Frantz MC, Bell-Temin H, Pope-Varsalona H, Gurkar AU, Nasto LA, Robinson RAS, Fuhrmann-Stroissnigg H, Czerwinska J, McGowan SJ, Cantu-Medellin N, Harris JB, Maniar S, Ross MA, Trussoni CE, LaRusso NF, Cifuentes-Pagano E, Pagano PJ, Tudek B, Vo NV, Rigatti LH, Opresko PL, Stolz DB, Watkins SC, Burd CE, Croix CMS, Siuzdak G, Yates NA, Robbins PD, Wang Y, Wipf P, Kelley EE, Niedernhofer LJ (2018) Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging. Redox Biol 17:259–273. https://doi.org/10.1016/j.redox.2018.04.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sorrentino JA, Krishnamurthy J, Tilley S, Alb JG Jr, Burd CE, Sharpless NE (2014) p16INK4a reporter mice reveal age-promoting effects of environmental toxicants. J Clin Invest 124(1):169–173. https://doi.org/10.1172/JCI70960

    Article  CAS  PubMed  Google Scholar 

  99. Choudhury AR, Ju Z, Djojosubroto MW, Schienke A, Lechel A, Schaetzlein S, Jiang H, Stepczynska A, Wang C, Buer J, Lee HW, von Zglinicki T, Ganser A, Schirmacher P, Nakauchi H, Rudolph KL (2007) Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet 39(1):99–105. https://doi.org/10.1038/ng1937

    Article  CAS  PubMed  Google Scholar 

  100. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC (1996) Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A 93(24):13742–13747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Robles SJ, Adami GR (1998) Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts. Oncogene 16(9):1113–1123. https://doi.org/10.1038/sj.onc.1201862

    Article  CAS  PubMed  Google Scholar 

  102. Stein GH, Drullinger LF, Soulard A, Dulic V (1999) Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 19(3):2109–2117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interf Cytokine Res 29(6):313–326. https://doi.org/10.1089/jir.2008.0027

    Article  CAS  Google Scholar 

  104. Csoka AB, English SB, Simkevich CP, Ginzinger DG, Butte AJ, Schatten GP, Rothman FG, Sedivy JM (2004) Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell 3(4):235–243. https://doi.org/10.1111/j.1474-9728.2004.00105.x

    Article  CAS  PubMed  Google Scholar 

  105. Yousefzadeh MJ, Schafer MJ, Noren Hooten N, Atkinson EJ, Evans MK, Baker DJ, Quarles EK, Robbins PD, Ladiges WC, LeBrasseur NK, Niedernhofer LJ (2018) Circulating levels of monocyte chemoattractant protein-1 as a potential measure of biological age in mice and frailty in humans. Aging Cell 17(2). https://doi.org/10.1111/acel.12706

  106. Nelson JA, Krishnamurthy J, Menezes P, Liu Y, Hudgens MG, Sharpless NE, Eron JJ Jr (2012) Expression of p16(INK4a) as a biomarker of T-cell aging in HIV-infected patients prior to and during antiretroviral therapy. Aging Cell 11(5):916–918. https://doi.org/10.1111/j.1474-9726.2012.00856.x

    Article  CAS  PubMed  Google Scholar 

  107. Sanoff HK, Deal AM, Krishnamurthy J, Torrice C, Dillon P, Sorrentino J, Ibrahim JG, Jolly TA, Williams G, Carey LA, Drobish A, Gordon BB, Alston S, Hurria A, Kleinhans K, Rudolph KL, Sharpless NE, Muss HB (2014) Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer. J Natl Cancer Inst 106(4):dju057. https://doi.org/10.1093/jnci/dju057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Rosko A, Hofmeister C, Benson D, Efebera Y, Huang Y, Gillahan J, Byrd JC, Burd CE (2015) Autologous hematopoietic stem cell transplant induces the molecular aging of T-cells in multiple myeloma. Bone Marrow Transplant 50(10):1379–1381. https://doi.org/10.1038/bmt.2015.143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Wood WA, Krishnamurthy J, Mitin N, Torrice C, Parker JS, Snavely AC, Shea TC, Serody JS, Sharpless NE (2016) Chemotherapy and stem cell transplantation increase p16(INK4a) expression, a biomarker of T-cell aging. EBioMedicine 11:227–238. https://doi.org/10.1016/j.ebiom.2016.08.029

    Article  PubMed  PubMed Central  Google Scholar 

  110. Lee BY, Han JA, Im JS, Morrone A, Johung K, Goodwin EC, Kleijer WJ, DiMaio D, Hwang ES (2006) Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5(2):187–195. https://doi.org/10.1111/j.1474-9726.2006.00199.x

    Article  CAS  PubMed  Google Scholar 

  111. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92(20):9363–9367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhao J, Fuhrmann-Stroissnigg H, Gurkar AU, Flores RR, Dorronsoro A, Stolz DB, St Croix CM, Niedernhofer LJ, Robbins PD (2017) Quantitative analysis of cellular senescence in culture and in vivo. Curr Protoc Cytom 79:9 51 51–59 51 25. https://doi.org/10.1002/cpcy.16

    Article  PubMed  Google Scholar 

  113. Gregg SQ, Gutierrez V, Robinson AR, Woodell T, Nakao A, Ross MA, Michalopoulos GK, Rigatti L, Rothermel CE, Kamileri I, Garinis GA, Stolz DB, Niedernhofer LJ (2012) A mouse model of accelerated liver aging caused by a defect in DNA repair. Hepatology 55(2):609–621. https://doi.org/10.1002/hep.24713

    Article  CAS  PubMed  Google Scholar 

  114. Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC, Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD (2012) NF-kappaB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest 122(7):2601–2612. https://doi.org/10.1172/JCI45785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Melk A, Schmidt BM, Takeuchi O, Sawitzki B, Rayner DC, Halloran PF (2004) Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int 65(2):510–520. https://doi.org/10.1111/j.1523-1755.2004.00438.x

    Article  CAS  PubMed  Google Scholar 

  116. Thompson LH (2012) Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography. Mutat Res 751(2):158–246. https://doi.org/10.1016/j.mrrev.2012.06.002

    Article  CAS  PubMed  Google Scholar 

  117. Takayama K, Kawakami Y, Lavasani M, Mu X, Cummins JH, Yurube T, Kuroda R, Kurosaka M, Fu FH, Robbins PD, Niedernhofer LJ, Huard J (2017) mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging. J Orthop Res 35(7):1375–1382. https://doi.org/10.1002/jor.23409

    Article  CAS  PubMed  Google Scholar 

  118. Khan SY, Awad EM, Oszwald A, Mayr M, Yin X, Waltenberger B, Stuppner H, Lipovac M, Uhrin P, Breuss JM (2017) Premature senescence of endothelial cells upon chronic exposure to TNFalpha can be prevented by N-acetyl cysteine and plumericin. Sci Rep 7:39501. https://doi.org/10.1038/srep39501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wiley CD, Velarde MC, Lecot P, Liu S, Sarnoski EA, Freund A, Shirakawa K, Lim HW, Davis SS, Ramanathan A, Gerencser AA, Verdin E, Campisi J (2016) Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab 23(2):303–314. https://doi.org/10.1016/j.cmet.2015.11.011

    Article  CAS  PubMed  Google Scholar 

  120. Bruunsgaard H, Skinhoj P, Pedersen AN, Schroll M, Pedersen BK (2000) Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol 121(2):255–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Hall BM, Balan V, Gleiberman AS, Strom E, Krasnov P, Virtuoso LP, Rydkina E, Vujcic S, Balan K, Gitlin LKI II, Consiglio CR, Gollnick SO, Chernova OB, Gudkov AV (2017) p16(Ink4a) and senescence-associated beta-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging 9(8):1867–1884. https://doi.org/10.18632/aging.101268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Niedernhofer LJ, Robbins PD (2018) Senotherapeutics for healthy ageing. Nat Rev Drug Discov 17(5):377. https://doi.org/10.1038/nrd.2018.44

    Article  CAS  PubMed  Google Scholar 

  123. Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T, White TA, Johnson KO, Stout MB, Mezera V, Giorgadze N, Jensen MD, LeBrasseur NK, Kirkland JL (2015) JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci U S A 112(46):E6301–E6310. https://doi.org/10.1073/pnas.1515386112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55(4):611–622. https://doi.org/10.1373/clinchem.2008.112797

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the NIH grants P01-AG043376 (PDR, LJN), U19-AG056278 (PDR, LJN), and Glenn Foundation (LJN, CEB).

Author information

Authors and Affiliations

  1. Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA

    Matthew J. Yousefzadeh Ph.D., Luise Angelini B.S., Paul D. Robbins Ph.D. & Laura J. Niedernhofer M.D., Ph.D.

  2. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA

    Matthew J. Yousefzadeh Ph.D., Luise Angelini B.S. & Paul D. Robbins Ph.D.

  3. Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA

    Matthew J. Yousefzadeh Ph.D., Kendra I. Melos B.S., Luise Angelini B.S. & Paul D. Robbins Ph.D.

  4. Department of Molecular Genetics, The Ohio State University, Columbus, OH, USA

    Christin E. Burd Ph.D.

  5. Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA

    Christin E. Burd Ph.D.

Authors
  1. Matthew J. Yousefzadeh Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kendra I. Melos B.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luise Angelini B.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christin E. Burd Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul D. Robbins Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura J. Niedernhofer M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura J. Niedernhofer M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. ERIBA, University Medical Center Groningen, Groningen, Groningen, The Netherlands

    Marco Demaria

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Yousefzadeh, M.J., Melos, K.I., Angelini, L., Burd, C.E., Robbins, P.D., Niedernhofer, L.J. (2019). Mouse Models of Accelerated Cellular Senescence. In: Demaria, M. (eds) Cellular Senescence. Methods in Molecular Biology, vol 1896. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8931-7_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8931-7_17

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8930-0

  • Online ISBN: 978-1-4939-8931-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation