Of flies, mice, and men: Evolutionarily conserved tissue damage responses and aging

Developmental Cell

Volumn 32, Issue 1, 2015, Pages 9-18

  Neves, Joana ^a   Demaria, Marco ^a   Campisi, Judith ^a,b   Jasper, Heinrich ^a  

^a BUCK INSTITUTE FOR RESEARCH ON AGING   (United States)

^b LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CXCL1 CHEMOKINE; DECAPENTAPLEGIC PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR; INTERLEUKIN 6; INTERLEUKIN 8; JANUS KINASE; LAMIN B; MITOGEN ACTIVATED PROTEIN KINASE P38; STAT PROTEIN; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN; WNT PROTEIN;

AGED; AGING; CANCER CELL; CARCINOGENESIS; CELL COMMUNICATION; CELL PROLIFERATION; CELL SURVIVAL; CONCEPTUAL FRAMEWORK; CYTOKINE PRODUCTION; DNA DAMAGE; DROSOPHILA MELANOGASTER; EPITHELIUM CELL; GENETIC CONSERVATION; HOMEOSTASIS; HUMAN; IMAGINAL DISC; INFLAMMATION; MORPHOGENESIS; MOUSE; NONHUMAN; ORGANOGENESIS; PARACRINE SIGNALING; PHENOTYPE; PLEIOTROPY; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TISSUE DEGENERATION; TISSUE INJURY; TISSUE REGENERATION; VERTEBRATE; ANIMAL; DIPTERA; EVOLUTION; MALE; PHYSIOLOGY; WOUND HEALING;

ANIMALIA; MUS;

AGING; ANIMALS; BIOLOGICAL EVOLUTION; DIPTERA; HOMEOSTASIS; HUMANS; MALE; MICE; WOUND HEALING;

EID: 84922350817     PISSN: 15345807     EISSN: 18781551     Source Type: Journal    
DOI: 10.1016/j.devcel.2014.11.028     Document Type: Review

References (104)

1. Acosta J.C., O'Loghlen A., Banito A., Guijarro M.V., Augert A., Raguz S., Fumagalli M., Da Costa M., Brown C., Popov N., et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008, 133:1006-1018.
2. Acosta J.C., Banito A., Wuestefeld T., Georgilis A., Janich P., Morton J.P., Athineos D., Kang T.W., Lasitschka F., Andrulis M., et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 2013, 15:978-990.
3. Adams P.D. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol. Cell 2009, 36:2-14.
4. Adler P.N., Bryant P.J. Participation of lethally irradiated imaginal disc tissue in pattern regulation in Drosophila. Dev. Biol. 1977, 60:298-304.
5. Agaisse H., Petersen U.M., Boutros M., Mathey-Prevot B., Perrimon N. Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury. Dev. Cell 2003, 5:441-450.
6. Arbouzova N.I., Zeidler M.P. JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development 2006, 133:2605-2616.
7. Baker D.J., Wijshake T., Tchkonia T., LeBrasseur N.K., Childs B.G., van de Sluis B., Kirkland J.L., van Deursen J.M. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011, 479:232-236.
8. Biteau B., Jasper H. EGF signaling regulates the proliferation of intestinal stem cells in Drosophila. Development 2011, 138:1045-1055.
9. Biteau B., Hochmuth C.E., Jasper H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 2008, 3:442-455.
10. Biteau B., Karpac J., Supoyo S., Degennaro M., Lehmann R., Jasper H. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet. 2010, 6:e1001159.
11. Biteau B., Hochmuth C.E., Jasper H. Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 2011, 9:402-411.
12. Brumby A.M., Richardson H.E. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 2003, 22:5769-5779.
13. Buchon N., Broderick N.A., Kuraishi T., Lemaitre B. Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol. 2010, 8:152.
14. Buchon N., Broderick N.A., Lemaitre B. Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat. Rev. Microbiol. 2013, 11:615-626.
15. Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr. Opin. Genet. Dev. 2011, 21:107-112.
16. Campisi J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 2013, 75:685-705.
17. Chen H., Zheng X., Zheng Y. Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell 2014, 159:829-843.
18. Choi N.H., Kim J.G., Yang D.J., Kim Y.S., Yoo M.A. Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor. Aging Cell 2008, 7:318-334.
19. Chung H.Y., Cesari M., Anton S., Marzetti E., Giovannini S., Seo A.Y., Carter C., Yu B.P., Leeuwenburgh C. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res. Rev. 2009, 8:18-30.
20. Classen A.K., Bunker B.D., Harvey K.F., Vaccari T., Bilder D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat. Genet. 2009, 41:1150-1155.
21. Clavería C., Giovinazzo G., Sierra R., Torres M. Myc-driven endogenous cell competition in the early mammalian embryo. Nature 2013, 500:39-44.
22. Coppé J.P., Kauser K., Campisi J., Beauséjour C.M. Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J.Biol. Chem. 2006, 281:29568-29574.
23. Coppé J.P., Patil C.K., Rodier F., Sun Y., Muñoz D.P., Goldstein J., Nelson P.S., Desprez P.Y., Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008, 6:2853-2868.
24. Coppé J.P., Desprez P.Y., Krtolica A., Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 2010, 5:99-118.
25. Coppé J.P., Patil C.K., Rodier F., Krtolica A., Beauséjour C.M., Parrinello S., Hodgson J.G., Chin K., Desprez P.Y., Campisi J. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE 2010, 5:e9188.
26. Davalos A.R., Kawahara M., Malhotra G.K., Schaum N., Huang J., Ved U., Beausejour C.M., Coppe J.P., Rodier F., Campisi J. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J.Cell Biol. 2013, 201:613-629.
27. de la Cova C., Abril M., Bellosta P., Gallant P., Johnston L.A. Drosophila myc regulates organ size by inducing cell competition. Cell 2004, 117:107-116.
28. de la Cova C., Senoo-Matsuda N., Ziosi M., Wu D.C., Bellosta P., Quinzii C.M., Johnston L.A. Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability. Cell Metab. 2014, 19:470-483.
29. Demaria M., Ohtani N., Youssef S.A., Rodier F., Toussaint W., Mitchell R.J., Laberge R., Vijg J., Van Steeg H., Dollé M.E.T., et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 2014, Published online December 11, 2014. 10.1016/j.devcel.2014.11.012.
30. Franceschi C. Inflammaging as a major characteristic of old people: can it be prevented or cured?. Nutr. Rev. 2007, 65:S173-S176.
31. Freund A., Patil C.K., Campisi J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 2011, 30:1536-1548.
32. Freund A., Laberge R.M., Demaria M., Campisi J. Lamin B1 loss is a senescence-associated biomarker. Mol. Biol. Cell 2012, 23:2066-2075.
33. Guo L., Karpac J., Tran S.L., Jasper H. PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell 2014, 156:109-122.
34. Harrison D.A., McCoon P.E., Binari R., Gilman M., Perrimon N. Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. Genes Dev. 1998, 12:3252-3263.
35. Hirabayashi S., Baranski T.J., Cagan R.L. Transformed Drosophila cells evade diet-mediated insulin resistance through wingless signaling. Cell 2013, 154:664-675.
36. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 1986, 324:73-76.
37. Hochmuth C.E., Biteau B., Bohmann D., Jasper H. Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 2011, 8:188-199.
38. Hudson M.M., Ness K.K., Gurney J.G., Mulrooney D.A., Chemaitilly W., Krull K.R., Green D.M., Armstrong G.T., Nottage K.A., Jones K.E., et al. Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 2013, 309:2371-2381.
39. Huh J.R., Guo M., Hay B.A. Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr. Biol. 2004, 14:1262-1266.
40. Iannello A., Thompson T.W., Ardolino M., Lowe S.W., Raulet D.H. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J.Exp. Med. 2013, 210:2057-2069.
41. Igaki T., Pagliarini R.A., Xu T. Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr. Biol. 2006, 16:1139-1146.
42. Jiang H., Patel P.H., Kohlmaier A., Grenley M.O., McEwen D.G., Edgar B.A. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 2009, 137:1343-1355.
43. Jiang H., Grenley M.O., Bravo M.J., Blumhagen R.Z., Edgar B.A. EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 2011, 8:84-95.
44. Jun J.I., Lau L.F. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat. Cell Biol. 2010, 12:676-685.
45. Kang T.W., Yevsa T., Woller N., Hoenicke L., Wuestefeld T., Dauch D., Hohmeyer A., Gereke M., Rudalska R., Potapova A., et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011, 479:547-551.
46. Karpowicz P., Perez J., Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 2010, 137:4135-4145.
47. Kondo S., Senoo-Matsuda N., Hiromi Y., Miura M. DRONC coordinates cell death and compensatory proliferation. Mol. Cell. Biol. 2006, 26:7258-7268.
48. Kortlever R.M., Higgins P.J., Bernards R. Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat. Cell Biol. 2006, 8:877-884.
49. Krizhanovsky V., Yon M., Dickins R.A., Hearn S., Simon J., Miething C., Yee H., Zender L., Lowe S.W. Senescence of activated stellate cells limits liver fibrosis. Cell 2008, 134:657-667.
50. Kuilman T., Michaloglou C., Vredeveld L.C.W., Douma S., van Doorn R., Desmet C.J., Aarden L.A., Mooi W.J., Peeper D.S. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 2008, 133:1019-1031.
51. Lee N., Maurange C., Ringrose L., Paro R. Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs. Nature 2005, 438:234-237.
52. Levy D.E., Lee C.K. What does Stat3 do?. J.Clin. Invest. 2002, 109:1143-1148.
53. Li W., Baker N.E. Engulfment is required for cell competition. Cell 2007, 129:1215-1225.
54. Lolo F.N., Casas-Tintó S., Moreno E. Cell competition time line: winners kill losers, which are extruded and engulfed by hemocytes. Cell Rep. 2012, 2:526-539.
55. Losick V.P., Fox D.T., Spradling A.C. Polyploidization and cell fusion contribute to wound healing in the adult Drosophila epithelium. Curr. Biol. 2013, 23:2224-2232.
56. Lujambio A., Akkari L., Simon J., Grace D., Tschaharganeh D.F., Bolden J.E., Zhao Z., Thapar V., Joyce J.A., Krizhanovsky V., Lowe S.W. Non-cell-autonomous tumor suppression by p53. Cell 2013, 153:449-460.
57. Martins V.C., Busch K., Juraeva D., Blum C., Ludwig C., Rasche V., Lasitschka F., Mastitsky S.E., Brors B., Hielscher T., et al. Cell competition is a tumour suppressor mechanism in the thymus. Nature 2014, 509:465-470.
58. Micchelli C.A., Perrimon N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 2006, 439:475-479.
59. Morata G., Ripoll P. Minutes: mutants of drosophila autonomously affecting cell division rate. Dev. Biol. 1975, 42:211-221.
60. Morata G., Shlevkov E., Pérez-Garijo A. Mitogenic signaling from apoptotic cells in Drosophila. Dev. Growth Differ. 2011, 53:168-176.
61. Moreno E. Is cell competition relevant to cancer?. Nat. Rev. Cancer 2008, 8:141-147.
62. Moreno E., Basler K. dMyc transforms cells into super-competitors. Cell 2004, 117:117-129.
63. Moreno E., Basler K., Morata G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 2002, 416:755-759.
64. Muñoz-Espín D., Cañamero M., Maraver A., Gómez-López G., Contreras J., Murillo-Cuesta S., Rodríguez-Baeza A., Varela-Nieto I., Ruberte J., Collado M., Serrano M. Programmed cell senescence during mammalian embryonic development. Cell 2013, 155:1104-1118.
65. Nakamura K., Nonaka H., Saito H., Tanaka M., Miyajima A. Hepatocyte proliferation and tissue remodeling is impaired after liver injury in oncostatin M receptor knockout mice. Hepatology 2004, 39:635-644.
66. Nechemia-Arbely Y., Barkan D., Pizov G., Shriki A., Rose-John S., Galun E., Axelrod J.H. IL-6/IL-6R axis plays a critical role in acute kidney injury. J.Am. Soc. Nephrol. 2008, 19:1106-1115.
67. Ohlstein B., Spradling A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 2006, 439:470-474.
68. Ohsawa S., Sugimura K., Takino K., Xu T., Miyawaki A., Igaki T. Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev. Cell 2011, 20:315-328.
69. Ohsawa S., Takemoto D., Igaki T. Dissecting tumour heterogeneity in flies: genetic basis of interclonal oncogenic cooperation. J.Biochem. 2014, 156:129-136.
70. Osman D., Buchon N., Chakrabarti S., Huang Y.T., Su W.C., Poidevin M., Tsai Y.C., Lemaitre B. Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division. J.Cell Sci. 2012, 125:5944-5949.
71. Parrinello S., Coppe J.P., Krtolica A., Campisi J. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J.Cell Sci. 2005, 118:485-496.
72. Pérez-Garijo A., Martín F.A., Morata G. Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila. Development 2004, 131:5591-5598.
73. Pérez-Garijo A., Martín F.A., Struhl G., Morata G. Dpp signaling and the induction of neoplastic tumors by caspase-inhibited apoptotic cells in Drosophila. Proc. Natl. Acad. Sci. USA 2005, 102:17664-17669.
74. Petrova E., López-Gay J.M., Rhiner C., Moreno E. Flower-deficient mice have reduced susceptibility to skin papilloma formation. Dis. Model. Mech. 2012, 5:553-561.
75. Prieur A., Peeper D.S. Cellular senescence invivo: a barrier to tumorigenesis. Curr. Opin. Cell Biol. 2008, 20:150-155.
76. Ren F., Wang B., Yue T., Yun E.Y., Ip Y.T., Jiang J. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc. Natl. Acad. Sci. USA 2010, 107:21064-21069.
77. Rera M., Bahadorani S., Cho J., Koehler C.L., Ulgherait M., Hur J.H., Ansari W.S., Lo T., Jones D.L., Walker D.W. Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab. 2011, 14:623-634.
78. Rera M., Clark R.I., Walker D.W. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc. Natl. Acad. Sci. USA 2012, 109:21528-21533.
79. Rhiner C., López-Gay J.M., Soldini D., Casas-Tinto S., Martín F.A., Lombardía L., Moreno E. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev. Cell 2010, 18:985-998.
80. Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012, 33:571-577.
81. Rodier F., Campisi J. Four faces of cellular senescence. J.Cell Biol. 2011, 192:547-556.
82. Rodier F., Coppé J.P., Patil C.K., Hoeijmakers W.A., Muñoz D.P., Raza S.R., Freund A., Campeau E., Davalos A.R., Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 2009, 11:973-979.
83. Rodrigues A.B., Zoranovic T., Ayala-Camargo A., Grewal S., Reyes-Robles T., Krasny M., Wu D.C., Johnston L.A., Bach E.A. Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis. Development 2012, 139:4051-4061.
84. Rudrapatna V.A., Bangi E., Cagan R.L. Caspase signalling in theabsence of apoptosis drives Jnk-dependent invasion. EMBO Rep. 2013, 14:172-177.
85. Ryoo H.D., Gorenc T., Steller H. Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways. Dev. Cell 2004, 7:491-501.
86. Sancho M., Di-Gregorio A., George N., Pozzi S., Sánchez J.M., Pernaute B., Rodríguez T.A. Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Dev. Cell 2013, 26:19-30.
87. Senoo-Matsuda N., Johnston L.A. Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc. Proc. Natl. Acad. Sci. USA 2007, 104:18543-18548.
88. Shaw R.L., Kohlmaier A., Polesello C., Veelken C., Edgar B.A., Tapon N. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 2010, 137:4147-4158.
89. Storer M., Mas A., Robert-Moreno A., Pecoraro M., Ortells M.C., Di Giacomo V., Yosef R., Pilpel N., Krizhanovsky V., Sharpe J., Keyes W.M. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 2013, 155:1119-1130.
90. Sun Y., Campisi J., Higano C., Beer T.M., Porter P., Coleman I., True L., Nelson P.S. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat. Med. 2012, 18:1359-1368.
91. Takino K., Ohsawa S., Igaki T. Loss of Rab5 drives non-autonomous cell proliferation through TNF and Ras signaling in Drosophila. Dev. Biol. 2014, 395:19-28.
92. Tamori Y., Deng W.M. Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia. Dev. Cell 2013, 25:350-363.
93. Tamori Y., Deng W.M. Compensatory cellular hypertrophy: the other strategy for tissue homeostasis. Trends Cell Biol. 2014, 24:230-237.
94. Tasdemir N., Lowe S.W. Senescent cells spread the word: non-cell autonomous propagation of cellular senescence. EMBO J. 2013, 32:1975-1976.
95. Uhlirova M., Jasper H., Bohmann D. Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. Proc. Natl. Acad. Sci. USA 2005, 102:13123-13128.
96. Villa del Campo C., Clavería C., Sierra R., Torres M. Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart. Cell Rep. 2014, 8:1741-1751.
97. Vincent J.P., Fletcher A.G., Baena-Lopez L.A. Mechanisms and mechanics of cell competition in epithelia. Nat. Rev. Mol. Cell Biol. 2013, 14:581-591.
98. Wajapeyee N., Serra R.W., Zhu X., Mahalingam M., Green M.R. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 2008, 132:363-374.
99. Wajapeyee N., Serra R.W., Zhu X., Mahalingam M., Green M.R. Role for IGFBP7 in senescence induction by BRAF. Cell 2010, 141:746-747.
100. Wang B., Hendricks D.T., Wamunyokoli F., Parker M.I. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006, 66:3071-3077.
101. Wang L., Zeng X., Ryoo H.D., Jasper H. Integration of UPRER and oxidative stress signaling in the control of intestinal stem cell proliferation. PLoS Genet. 2014, 10:e1004568.
102. Xue W., Zender L., Miething C., Dickins R.A., Hernando E., Krizhanovsky V., Cordon-Cardo C., Lowe S.W. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007, 445:656-660.
103. Yang P., Wen H., Ou S., Cui J., Fan D. IL-6 promotes regeneration and functional recovery after cortical spinal tract injury by reactivating intrinsic growth program of neurons and enhancing synapse formation. Exp. Neurol. 2012, 236:19-27.
104. Yoshimoto S., Loo T.M., Atarashi K., Kanda H., Sato S., Oyadomari S., Iwakura Y., Oshima K., Morita H., Hattori M., et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013, 499:97-101.