1932

Abstract

Cellular senescence is implicated in a wide range of physiological and pathological conditions throughout an organism's entire lifetime. In particular, it has become evident that senescence plays a causative role in aging and age-associated disorders. This is not due simply to the loss of function of senescent cells. Instead, the substantial alterations of the cellular activities of senescent cells, especially the array of secretory factors, impact the surrounding tissues or even entire organisms. Such non-cell-autonomous functionality is largely coordinated by tissue-specific genes, constituting a cell fate–determining state. Senescence can be viewed as a gain-of-function phenotype or a process of cell identity shift. Cellular functionality or lineage-specific gene expression is tightly linked to the cell type–specific epigenetic landscape, reinforcing the heterogeneity of senescence across cell types. Here, we aim to define the senescence cellular functionality and epigenetic features that may contribute to the gain-of-function phenotype.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-120420-013537
2022-10-06
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/38/1/annurev-cellbio-120420-013537.html?itemId=/content/journals/10.1146/annurev-cellbio-120420-013537&mimeType=html&fmt=ahah

Literature Cited

  1. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P et al. 2013. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15:8978–90
    [Google Scholar]
  2. Aguayo-Mazzucato C, Andle J, Lee TB, Midha A, Talemal L et al. 2019. Acceleration of β cell aging determines diabetes and senolysis improves disease outcomes. Cell Metab 30:1129–42.e4
    [Google Scholar]
  3. Aird KM, Iwasaki O, Kossenkov AV, Tanizawa H, Fatkhutdinov N et al. 2016. HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci. J. Cell Biol. 215:3325–34
    [Google Scholar]
  4. Almeida N, Chung MWH, Drudi EM, Engquist EN, Hamrud E et al. 2021. Employing core regulatory circuits to define cell identity. EMBO J 40:10e106785
    [Google Scholar]
  5. Altschuler SJ, Wu LF. 2010. Cellular heterogeneity: do differences make a difference?. Cell 141:4559–63
    [Google Scholar]
  6. Avrahami D, Li C, Zhang J, Schug J, Avrahami R et al. 2015. Aging-dependent demethylation of regulatory elements correlates with chromatin state and improved β cell function. Cell Metab. 22:4619–32
    [Google Scholar]
  7. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ et al. 2016. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530:7589184–89
    [Google Scholar]
  8. Baker DJ, Wijshake T, Tchkonia T, Lebrasseur NK, Childs BG et al. 2011. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479:7372232–36
    [Google Scholar]
  9. Banito A, Rashid ST, Acosta JC, Li SD, Pereira CF et al. 2009. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23:182134–39
    [Google Scholar]
  10. Basisty N, Kale A, Jeon OH, Kuehnemann C, Payne T et al. 2020. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLOS Biol 18:1e3000599
    [Google Scholar]
  11. Beauséjour CM, Campisi J. 2006. Ageing: balancing regeneration and cancer. Nature 443:7110404–5
    [Google Scholar]
  12. Beauséjour CM, Krtolica A, Galimi F, Narita M, Lowe SW et al. 2003. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 22:164212–22
    [Google Scholar]
  13. Becker JS, Nicetto D, Zaret KS. 2016. H3K9me3-dependent heterochromatin: barrier to cell fate changes. Trends Genet 32:129–41
    [Google Scholar]
  14. Bemiller PM, Lee L-H. 1978. Nucleolar changes in senescing WI-38 cells. Mech. Ageing Dev. 8:6417–27
    [Google Scholar]
  15. Bhat P, Honson D, Guttman M. 2021. Nuclear compartmentalization as a mechanism of quantitative control of gene expression. Nat. Rev. Mol. Cell Biol. 22:10653–70
    [Google Scholar]
  16. Biran A, Perelmutter M, Gal H, Burton DGA, Ovadya Y et al. 2015. Senescent cells communicate via intercellular protein transfer. Genes Dev 29:8791–802
    [Google Scholar]
  17. Birch J, Gil J. 2020. Senescence and the SASP: many therapeutic avenues. Genes Dev 34:23–241565–76
    [Google Scholar]
  18. Bizhanova A, Kaufman PD. 2021. Close to the edge: heterochromatin at the nucleolar and nuclear peripheries. Biochim. Biophys. Acta Gene Regul. Mech. 1864:1194666
    [Google Scholar]
  19. Botchkarev VA, Gdula MR, Mardaryev AN, Sharov AA, Fessing MY. 2012. Epigenetic regulation of gene expression in keratinocytes. J. Invest. Dermatol. 132:112505–21
    [Google Scholar]
  20. Boumendil C, Hari P, Olsen KCF, Acosta JC, Bickmore WA. 2019. Nuclear pore density controls heterochromatin reorganization during senescence. Genes Dev 33:144–49
    [Google Scholar]
  21. Busslinger GA, Stocsits RR, Van Der Lelij P, Axelsson E, Tedeschi A et al. 2017. Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature 544:7651503–7
    [Google Scholar]
  22. Chan ASL, Narita M. 2019. Short-term gain, long-term pain: the senescence life cycle and cancer. Genes Dev 33:3–4127–43
    [Google Scholar]
  23. Chandra T, Ewels PA, Schoenfelder S, Furlan-Magaril M, Wingett SW et al. 2015. Global reorganization of the nuclear landscape in senescent cells. Cell Rep 10:4471–83
    [Google Scholar]
  24. Chandra T, Kirschner K, Thuret JY, Pope BD, Ryba T et al. 2012. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol. Cell 47:2203–14
    [Google Scholar]
  25. Chiche A, Le Roux I, von Joest M, Sakai H, Aguín SB et al. 2017. Injury-induced senescence enables in vivo reprogramming in skeletal muscle. Cell Stem Cell 20:3407–14.e4
    [Google Scholar]
  26. Chuprin A, Gal H, Biron-Shental T, Biran A, Amiel A et al. 2013. Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. Genes Dev 27:212356–66
    [Google Scholar]
  27. Corpet A, Kleijwegt C, Roubille S, Juillard F, Jacquet K et al. 2020. PML nuclear bodies and chromatin dynamics: catch me if you can!. Nucleic Acids Res. 48:2111890–912
    [Google Scholar]
  28. Corpet A, Olbrich T, Gwerder M, Fink D, Stucki M. 2014. Dynamics of histone H3.3 deposition in proliferating and senescent cells reveals a DAXX-dependent targeting to PML-NBs important for pericentromeric heterochromatin organization. Cell Cycle 13:2249–67
    [Google Scholar]
  29. Criscione SW, De Cecco M, Siranosian B, Zhang Y, Kreiling JA et al. 2016. Reorganization of chromosome architecture in replicative cellular senescence. Sci. Adv. 2:2e1500882
    [Google Scholar]
  30. De Cecco M, Criscione SW, Peckham EJ, Hillenmeyer S, Hamm EA et al. 2013. Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell 12:2247–56
    [Google Scholar]
  31. De Cecco M, Ito T, Petrashen AP, Elias AE, Skvir NJ et al. 2019. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature 566:774273–78
    [Google Scholar]
  32. Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F. 2021. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 22:275–95
    [Google Scholar]
  33. Dillinger S, Straub T, Nemeth A. 2017. Nucleolus association of chromosomal domains is largely maintained in cellular senescence despite massive nuclear reorganisation. PLOS ONE 12:6e0178821
    [Google Scholar]
  34. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y et al. 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:7398376–80
    [Google Scholar]
  35. Dowen JM, Bilodeau S, Orlando DA, Hübner MR, Abraham BJ et al. 2013. Multiple structural maintenance of chromosome complexes at transcriptional regulatory elements. Stem Cell Rep 1:5371–78
    [Google Scholar]
  36. Dreesen O, Chojnowski A, Ong PF, Zhao TY, Common JE et al. 2013. Lamin B1 fluctuations have differential effects on cellular proliferation and senescence. J. Cell Biol. 200:5605–17
    [Google Scholar]
  37. Duarte LF, Young ARJ, Wang Z, Wu HA, Panda T et al. 2014. Histone H3.3 and its proteolytically processed form drive a cellular senescence programme. Nat. Commun. 5:5210
    [Google Scholar]
  38. Feizi A, Gatto F, Uhlen M, Nielsen J. 2017. Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome. npj Syst. Biol. Appl.322
    [Google Scholar]
  39. Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW. 2000. PML is induced by oncogenic ras and promotes premature senescence. Genes Dev 14:162015–27
    [Google Scholar]
  40. Freund A, Laberge RM, Demaria M, Campisi J. 2012. Lamin B1 loss is a senescence-associated biomarker. Mol. Biol. Cell 23:112066–75
    [Google Scholar]
  41. Fumagalli M, Rossiello F, Clerici M, Barozzi S, Cittaro D et al. 2012. Telomeric DNA damage is irreparable and causes persistent DNA damage response activation. Nat. Cell Biol. 14:4355–65
    [Google Scholar]
  42. Funayama R, Saito M, Tanobe H, Ishikawa F. 2006. Loss of linker histone H1 in cellular senescence. J. Cell Biol. 175:6869–80
    [Google Scholar]
  43. Ghosh RP, Meyer BJ. 2021. Spatial organization of chromatin: emergence of chromatin structure during development. Annu. Rev. Cell Dev. Biol. 37:199–232
    [Google Scholar]
  44. Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O et al. 2019. Cellular senescence: defining a path forward. Cell 179:4813–27
    [Google Scholar]
  45. Grubert F, Srivas R, Spacek DV, Kasowski M, Ruiz-Velasco M et al. 2020. Landscape of cohesin-mediated chromatin loops in the human genome. Nature 583:7818737–43
    [Google Scholar]
  46. Hayflick L, Moorhead PS. 1961. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25:3585–621
    [Google Scholar]
  47. Helman A, Klochendler A, Azazmeh N, Gabai Y, Horwitz E et al. 2016. p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion. Nat. Med. 22:4412–20
    [Google Scholar]
  48. Hewitt G, Jurk D, Marques FDM, Correia-Melo C, Hardy T et al. 2012. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat. Commun. 3:708
    [Google Scholar]
  49. Hoare M, Ito Y, Kang TW, Weekes MP, Matheson NJ et al. 2016. NOTCH1 mediates a switch between two distinct secretomes during senescence. Nat. Cell Biol. 18:9979–92
    [Google Scholar]
  50. Hoare M, Narita M 2018. The power behind the throne: senescence and the hallmarks of cancer. Annu. Rev. Cancer Biol 2175–94
  51. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O et al. 2009. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460:72591132–35
    [Google Scholar]
  52. Ito Y, Hoare M, Narita M. 2017. Spatial and temporal control of senescence. Trends Cell Biol 27:11820–32
    [Google Scholar]
  53. Iwasaki O, Tanizawa H, Kim KD, Kossenkov A, Nacarelli T et al. 2019. Involvement of condensin in cellular senescence through gene regulation and compartmental reorganization. Nat. Commun. 10:5688
    [Google Scholar]
  54. Jackson B, Tilli CMLJ, Hardman MJ, Avilion AA, MacLeod MC et al. 2005. Late cornified envelope family in differentiating epithelia—response to calcium and ultraviolet irradiation. J. Invest. Dermatol. 124:51062–70
    [Google Scholar]
  55. Jin F, Li Y, Dixon JR, Selvaraj S, Ye Z et al. 2013. A high-resolution map of three-dimensional chromatin interactome in human cells. Nature 503:7475290–94
    [Google Scholar]
  56. Kagawa S, Natsuizaka M, Whelan KA, Facompre N, Naganuma S et al. 2015. Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities. Oncogene 34:182347–59
    [Google Scholar]
  57. Klemm SL, Shipony Z, Greenleaf WJ. 2019. Chromatin accessibility and the regulatory epigenome. Nat. Rev. Genet. 20:4207–20
    [Google Scholar]
  58. Kumari R, Jat P. 2021. Mechanisms of cellular senescence: cell cycle arrest and senescence associated secretory phenotype. Front. Cell Dev. Biol. 9:645593
    [Google Scholar]
  59. Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB et al. 2017. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547:7662236–40
    [Google Scholar]
  60. Lenain C, De Graaf CA, Pagie L, Visser NL, De Haas M et al. 2017. Massive reshaping of genome-nuclear lamina interactions during oncogene-induced senescence. Genome Res 27:101634–44
    [Google Scholar]
  61. Lessard F, Igelmann S, Trahan C, Huot G, Saint-Germain E et al. 2018. Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway. Nat. Cell Biol. 20:7789–99
    [Google Scholar]
  62. Levi N, Papismadov N, Solomonov I, Sagi I, Krizhanovsky V. 2020. The ECM path of senescence in aging: components and modifiers. FEBS J 287:132636–46
    [Google Scholar]
  63. Li H, Collado M, Villasante A, Strati K, Ortega S et al. 2009. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460:72591136–39
    [Google Scholar]
  64. Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T et al. 2009. Comprehensive mapping of long range interactions reveals folding principles of the human genome. Science 326:5950289–93
    [Google Scholar]
  65. Lin AW, Lowe SW. 2001. Oncogenic ras activates the ARF-p53 pathway to suppress epithelial cell transformation. PNAS 98:95025–30
    [Google Scholar]
  66. Liu J-Y, Souroullas GP, Diekman BO, Krishnamurthy J, Hall BM et al. 2019. Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence. PNAS 116:72603–11
    [Google Scholar]
  67. Marión RM, Strati K, Li H, Murga M, Blanco R et al. 2009. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460:72591149–53
    [Google Scholar]
  68. Marthandan S, Baumgart M, Priebe S, Groth M, Schaer J et al. 2016. Conserved senescence associated genes and pathways in primary human fibroblasts detected by RNA-seq. PLOS ONE 11:5e0154531
    [Google Scholar]
  69. McKinley KL, Castillo-Azofeifa D, Klein OD. 2020. Tools and concepts for interrogating and defining cellular identity. Cell Stem Cell 26:5632–56
    [Google Scholar]
  70. Meuleman W, Peric-Hupkes D, Kind J, Beaudry JB, Pagie L et al. 2013. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Genome Res 23:2270–80
    [Google Scholar]
  71. Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z et al. 2018. Senescence-associated reprogramming promotes cancer stemness. Nature 553:768696–100
    [Google Scholar]
  72. Morris SA. 2019. The evolving concept of cell identity in the single cell era. Development 146:12dev169748
    [Google Scholar]
  73. Mosteiro L, Pantoja C, Alcazar N, Marión RM, Chondronasiou D et al. 2016. Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science 354:6315aaf4445
    [Google Scholar]
  74. Muñoz-Espín D, Cañamero M, Maraver A, Gómez-López G, Contreras J et al. 2013. Programmed cell senescence during mammalian embryonic development. Cell 155:51104–18
    [Google Scholar]
  75. Narita M, Narita M, Krizhanovsky V, Nuñez S, Chicas A et al. 2006. A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation. Cell 126:3503–14
    [Google Scholar]
  76. Narita M, Nũnez S, Heard E, Narita M, Lin AW et al. 2003. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:6703–16
    [Google Scholar]
  77. Nelson DM, Jaber-Hijazi F, Cole JJ, Robertson NA, Pawlikowski JS et al. 2016. Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability. Genome Biol 17:1158
    [Google Scholar]
  78. Nelson G, Wordsworth J, Wang C, Jurk D, Lawless C et al. 2012. A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11:2345–49
    [Google Scholar]
  79. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I et al. 2012. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:7398381–85
    [Google Scholar]
  80. Olan I, Parry AJ, Schoenfelder S, Narita M, Ito Y et al. 2020. Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence. Nat. Commun. 11:16049
    [Google Scholar]
  81. Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J. 2009. Cell surface-bound IL-1α is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. PNAS 106:4017031–36
    [Google Scholar]
  82. Parry AJ, Hoare M, Bihary D, Hänsel-Hertsch R, Smith S et al. 2018. NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence. Nat. Commun. 9:11840
    [Google Scholar]
  83. Parry AJ, Narita M. 2016. Old cells, new tricks: chromatin structure in senescence. Mamm. Genome 27:7–8320–31
    [Google Scholar]
  84. Pearson M, Carbone R, Sebastiani C, Cloce M, Fagloll M et al. 2000. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406:6792207–10
    [Google Scholar]
  85. Pérez-Mancera PA, Young ARJ, Narita M. 2014. Inside and out: the activities of senescence in cancer. Nat. Rev. Cancer 14:8547–58
    [Google Scholar]
  86. Phanstiel DH, Van Bortle K, Spacek D, Hess GT, Shamim MS et al. 2017. Static and dynamic DNA loops form AP-1 bound activation hubs during macrophage development. Mol. Cell 67:61037–48.e6
    [Google Scholar]
  87. Rai TS, Adams PD. 2012. Lessons from senescence: chromatin maintenance in non-proliferating cells. Biochim. Biophys. Acta Gene Regul. Mech. 1819:3–4322–31
    [Google Scholar]
  88. Rai TS, Cole JJ, Nelson DM, Dikovskaya D, Faller WJ et al. 2014. HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia. Genes Dev 28:242712–25
    [Google Scholar]
  89. Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID et al. 2014. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:71665–80
    [Google Scholar]
  90. Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC et al. 2017. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev 31:2172–83
    [Google Scholar]
  91. Sadaie M, Salama R, Carroll T, Tomimatsu K, Chandra T et al. 2013. Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence. Genes Dev 27:161800–8
    [Google Scholar]
  92. Salama R, Sadaie M, Hoare M, Narita M. 2014. Cellular senescence and its effector programs. Genes Dev 28:299–114
    [Google Scholar]
  93. Salzer MC, Lafzi A, Berenguer-Llergo A, Youssif C, Castellanos A et al. 2018. Identity noise and adipogenic traits characterize dermal fibroblast aging. Cell 175:61575–90.e22
    [Google Scholar]
  94. Sati S, Bonev B, Szabo Q, Jost D, Bensadoun P et al. 2020. 4D genome rewiring during oncogene-induced and replicative senescence. Mol. Cell 78:3522–38.e9
    [Google Scholar]
  95. Sen P, Lan Y, Li CY, Sidoli S, Donahue G et al. 2019. Histone acetyltransferase p300 induces de novo super-enhancers to drive cellular senescence. Mol. Cell 73:4684–98.e8
    [Google Scholar]
  96. Setty M, Kiseliovas V, Levine J, Gayoso A, Mazutis L, Pe'er D 2019. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37:4451–60
    [Google Scholar]
  97. Shah PP, Donahue G, Otte GL, Capell BC, Nelson DM et al. 2013. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev 27:161787–99
    [Google Scholar]
  98. Sharpless NE, DePinho RA. 2007. How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 8:9703–13
    [Google Scholar]
  99. Shay JW, Wright WE. 2000. Hayflick, his limit, and cellular ageing. Nat. Rev. Mol. Cell Biol. 1:72–76
    [Google Scholar]
  100. Sheekey E, Narita M. 2021. p53 in senescence – it's a marathon not a sprint. FEBS J https://doi.org/10.1111/febs.16325
    [Crossref] [Google Scholar]
  101. Shimi T, Butin-Israeli V, Adam SA, Hamanaka RB, Goldman AE et al. 2011. The role of nuclear lamin B1 in cell proliferation and senescence. Genes Dev 25:242579–93
    [Google Scholar]
  102. Solovei I, Kreysing M, Lanctôt C, Kösem S, Peichl L et al. 2009. Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137:2356–68
    [Google Scholar]
  103. Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S et al. 2013. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152:3584–98
    [Google Scholar]
  104. Sonawane AR, Platig J, Fagny M, Chen CY, Paulson JN et al. 2017. Understanding tissue-specific gene regulation. Cell Rep 21:41077–88
    [Google Scholar]
  105. Stadhouders R, Filion GJ, Graf T. 2019. Transcription factors and 3D genome conformation in cell-fate decisions. Nature 569:7756345–54
    [Google Scholar]
  106. Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC et al. 2013. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155:51119–30
    [Google Scholar]
  107. Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X, Karpen GH. 2017. Phase separation drives heterochromatin domain formation. Nature 547:7662241–45
    [Google Scholar]
  108. Swanson EC, Manning B, Zhang H, Lawrence JB. 2013. Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. J. Cell Biol. 203:6929–42
    [Google Scholar]
  109. Takasugi M. 2018. Emerging roles of extracellular vesicles in cellular senescence and aging. Aging Cell 17:2e12734
    [Google Scholar]
  110. Tasdemir N, Banito A, Roe JS, Alonso-Curbelo D, Camiolo M et al. 2016. BRD4 connects enhancer remodeling to senescence immune surveillance. Cancer Discov 6:6613–29
    [Google Scholar]
  111. Tomimatsu K, Bihary D, Olan I, Parry AJ, Schoenfelder S et al. 2021. Locus-specific induction of gene expression from heterochromatin loci during cellular senescence. Nat. Aging 2:131–45
    [Google Scholar]
  112. Tu Z, Zhuang X, Yao Y-G, Zhang R. 2013. BRG1 is required for formation of senescence-associated heterochromatin foci induced by oncogenic RAS or BRCA1 loss. Mol. Cell. Biol. 33:91819–29
    [Google Scholar]
  113. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P et al. 2015. Tissue-based map of the human proteome. Science 347:62201260419
    [Google Scholar]
  114. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W et al. 2009. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460:72591145–48
    [Google Scholar]
  115. Van Deursen JM. 2014. The role of senescent cells in ageing. Nature 509:7501439–46
    [Google Scholar]
  116. Vernier M, Bourdeau V, Gaumont-Leclerc MF, Moiseeva O, Bégin V et al. 2011. Regulation of E2Fs and senescence by PML nuclear bodies. Genes Dev 25:141–50
    [Google Scholar]
  117. Wagner W. 2019. The link between epigenetic clocks for aging and senescence. Front. Genet. 10:303
    [Google Scholar]
  118. Wallis R, Mizen H, Bishop CL. 2020. The bright and dark side of extracellular vesicles in the senescence-associated secretory phenotype. Mech. Ageing Dev. 189:111263
    [Google Scholar]
  119. Wang B, Kohli J, Demaria M. 2020. Senescent cells in cancer therapy: friends or foes?. Trends Cancer 6:10838–57
    [Google Scholar]
  120. Xie W, Baylin SB, Easwaran H. 2019. DNA methylation in senescence, aging and cancer. Oncoscience 6:1–2291–93
    [Google Scholar]
  121. Ye X, Zerlanko B, Zhang R, Somaiah N, Lipinski M et al. 2007. Definition of pRB- and p53-dependent and -independent steps in HIRA/ASF1a-mediated formation of senescence-associated heterochromatin foci. Mol. Cell. Biol. 27:72452–65
    [Google Scholar]
  122. Ye Z, Sarkar CA. 2018. Towards a quantitative understanding of cell identity. Trends Cell Biol 28:121030–48
    [Google Scholar]
  123. Yokoyama Y, Zhu H, Zhang R, Noma KI. 2015. A novel role for the condensin II complex in cellular senescence. Cell Cycle 14:132160–70
    [Google Scholar]
  124. Zhang R, Chen W, Adams PD 2007. Molecular dissection of formation of senescence-associated heterochromatin foci. Mol. Cell. Biol. 27:62343–58
    [Google Scholar]
  125. Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W et al. 2005. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev. Cell 8:119–30
    [Google Scholar]
  126. Zhu H, Narita M, Joseph J, Krainer G, Arter W et al. 2021. The chromatin regulator HMGA1a undergoes phase separation in the nucleus. bioRxiv 464384. https://doi.org/10.1101/2021.10.14.464384
    [Crossref]
  127. Zhu X, Chen Z, Shen W, Huang G, Sedivy JM et al. 2021. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct. Target Ther. 6:1245
    [Google Scholar]
  128. Zirkel A, Nikolic M, Sofiadis K, Mallm JP, Brackley CA et al. 2018. HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types. Mol. Cell 70:4730–44.e6
    [Google Scholar]
/content/journals/10.1146/annurev-cellbio-120420-013537
Loading
/content/journals/10.1146/annurev-cellbio-120420-013537
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error