Aging and related diseases: Research progress

Progress in Biochemistry and Biophysics

Volumn 41, Issue 3, 2014, Pages 215-230

  Liu, Jun Ping ^a,b,c  

^a HANGZHOU NORMAL UNIVERSITY   (China)

^b MONASH UNIVERSITY   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Autophagy; Cell aging; Endoplasmic reticulum; Longevity; Lysosome; Mitochondria; Senescence; Stem cells; Telomere

Indexed keywords

EID: 84903168669     PISSN: 10003282     EISSN: None     Source Type: Journal    
DOI: 10.3724/SP.J.1206.2014.00036     Document Type: Review

References (174)

1. Arends M, van Dussen L, Biegstraaten M, et al. Malignancies and monoclonal gammopathy in Gaucher disease: A systematic review of the literature. Br J Haematol, 2013, 161 (6): 832-842 (DOI: 10.1111/bjh.l2335).
2. Cox C J, Sharma M, Leckman J F, et al. Brain human monoclonal autoantibody from Sydenham chorea targets dopaminergic neurons in transgenic mice and signals dopamine D2 receptor: implications in human disease. J Immunol, 2013, 191(11): 5524-5541 (DOI: 10.4049/jimmunol.l 102592).
3. Kakizoe T, Tanooka H, Tanaka K, et al. Single-cell origin of bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in mice with cellular mosaicism. Gann, 1983, 74(4): 462-465.
4. Rinaldi F, Mairs R J, Wheldon T E. et al. Clonality analysis suggests that early-onset acute lymphoblastic leukaemia is of single-cell origin and implies no major role for germ cell mutations in parents. Br J Cancer, 1999, 80(5-6): 909-913(001: 10.1038/sj. bjc.6690440).
5. Pistoia V, Roncella S, Di Celle P F, et al. Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. Blood, 1991, 78(3): 797-804.
6. Cleary M L, Galili N, Trela M, et al. Single cell origin of bigenotypic and biphenotypic B cell proliferations in human follicular lymphomas. J Exp Med, 1988, 167(2): 582-597.
7. Tanooka H, Tanaka K. Evidence for single-cell origin of 3-methylcholanthrene-induced fibrosarcomas in mice with cellular mosaicism. Cancer Res, 1982, 42(5): 1856-1858.
8. Tchkonia T, Zhu Y, van Deursen J, et al. Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities. J Clin Invest, 2013, 123(3): 966-972(DOI: 10.1172/JCI64098).
9. Acosta J C, Banito A, Wuestefeld T, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol, 2013, 15(18): 978-990(001: 10.1038/ncb2784).
10. Hoare M, Narita M. Transmitting senescence to the cell neighbourhood. Nat Cell Biol, 2013, 15 (8): 887-889 (DOI: 10. 1038/ncb2811).
11. Zhao Y, Chen F, Chen S, et al. The Parkinson's disease-associated gene PINK1 protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Dipl. J Neurochem, 2013(001: 10.111 l/jnc.12340).
12. Yoshimoto S, Loo T M, Atarashi K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature, 2013, 499 (7456): 97-101 (DOI: 10.1038/nature12347).
13. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol, 2013, 75: 685-705 (DOI: 10.1146/annurev-physiol- 030212-183653).
14. Coppe J P, Desprez P Y, Krtolica A, et al. The senescence-associated secretory phenotype: The dark side of tumor suppression. Annu Rev Pathol, 2013, 5: 99-118 (DOI: 10.1146/annurev-pathol-121808-102144).
15. Baker D J, Wijshake T, Tchkonia T, et al. Clearance of pl6Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 2011, 479 (7372): 232-236 (DOI: 10.1038/nature10600).
16. Mitteldorf J, Pepper J W. How can evolutionary theory accommodate recent empirical results on organismal senescence. Theory Biosci, 2007, 126 (1): 3-8 (DOI: 10.1007/sl2064-007- 0001-0).
17. de Jesus B B, Blasco M A. Assessing cell and organ senescence biomarkers. Circ Res, 2012, 111 (1): 97-109 (DOI: 10.1161/CIRCRESAHA. 111.247866).
18. Fine, R. E. Vesicles without clathrin: intermediates in bulk flow exocytosis. CeU, 1989, 58(4): 609-610.
19. Chen Y, Dorn G W 2nd. PINKl-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science, 2013, 340(6131): 471-475(DOI: 10.1126/science.l231031).
20. Hayflick L, Moorhead P S. The serial cultivation of human diploid cell strains. Exp Cell Res, 1961(Dec, 25): 585-621.
21. Liu J P, Nicholls C, Chen S M, et al. Strategies of treating cancer by cytokine regulation of chromosome end remodelling. Clin Exp Pharmacol Physiol, 2010, 37(1): 88-92(DOI: 10.1111/j.l440-1681. 2009.05251.x).
22. Bayne S, Jones M E, Li H, et al. Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice. Cell Res, 2008, 18(11): 1141-1150(001: 10.1038/cr.2008.291).
23. Li H, Liu J P. Signaling on telomerase: A master switch in cell aging and immortalization. Biogerontology, 2002, 3(1-2): 107-116.
24. Liu J P. Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J, 1999, 13(15): 2091-2104.
25. Kaplon J, Zheng L, Meissl K, et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature, 2013, 498(7452): 109-112 (DOI: 10.1038/naturel2154).
26. Di Micco R, Fumagalli M, Cicalese A, et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature, 2006, 444 (7119): 638-642 (DOI: 10.1038/nature05327).
27. Bartkova J, Rezaei N, Liontos M, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature, 2006, 444(7119): 633-637 (DOI: 10.1038/nature05268).
28. Jiang P, Du W, Mancuso A, et al. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature, 2013, 493(7434): 689-693(DOI: 10.1038/naturell776).
29. Banito A, Lowe S W. A new development in senescence. Cell, 2013, 155(5): 977-978(DOI: 10.1016/j.cell.2013.10.050).
30. Munoz-Espin D, Canamero M, Maraver A, et al. Programmed cell senescence during mammalian embryonic development. Cell, 2013, 155(5): 1104-1118(DOI: 10.1016/j .cell.2013.10.019).
31. Senescence and cell death. Nature, 2001, 409(6823): 1123-1124.
32. Jones O R, Scheuerlein A, Salguero-Gomez R, et al. Diversity of ageing across the tree of life. Nature, 2014, 505(7482): 169-173 (DOI: 10.1038/nature12789).
33. Flatt T. A new definition of aging?. Front Genet, 2012, 3: 148(DOI: 10.3389/fgene.2012.00148).
34. Signer R A, Morrison S J. Mechanisms that regulate stem cell aging and life span. Cell Stem Cell, 2013, 12 (2): 152-165 (DOI: 10.1016/j.stem.2013.01. 001).
35. Rodgers J T, Rando T A. Sprouting a new take on stem cell aging. EMBO J, 2012, 31 (21): 4103-4105 (DOI: 10.1038/emboj.2012. 281).
36. Jones L S, Bemdtson W E. A quantitative study of Sertoli cell and germ cell populations as related to sexual development and aging in the stallion. Biol Reprod, 1986, 35(1): 138-148.
37. Cohen G. The pathobiology of Parkinson's disease: biochemical aspects of dopamine neuron senescence. J Neural Transm Suppl, 1983, 19: 89-103.
38. Yang X, Doser T A, Fang C X, et al. Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress. FASEB J, 2006, 20(7): 1024-1026(001: 10.1096/05-5288).
39. Dong W, Cheng S, Huang F, et al. Mitochondrial dysfunction in long-term neuronal cultures mimics changes with aging. Med Sci Monit, 2011, 17(4): BR91-BR96(DOI: 10.12659/MSM.881706).
40. Geng Y Q, Guan J T, Xu X, et al. Senescence-associated beta-galactosidase activity expression in aging hippocampal neurons. Biochem Biophys Res Commun, 2010, 396(4): 866-869 (DOI: 10.1016/j .bbrc.2010.05.011).
41. Uehara T, Nakamura T, Yao D, et al. S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature, 2006, 441 (7092): 513-517 (DOI: 10.1038/nature04782).
42. Johnson M S, Mitchell R, Thomson F J. The priming effect of luteinizing hormone-releasing hormone (LHRH) but not LHRH-induced gonadotropin release, can be prevented by certain protein kinase C inhibitors. Mol Cell Endocrinol, 1992, 85 (3): 183-193.
43. Ross J M, Stewart J B, Hagstrom E, et al. Gennline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature, 2013, 501(7467): 412-415 (DOI: 10.1038/naturel2474).
44. Trifunovic A, Wredenberg A, Falkenberg M, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 2004, 429(6990): 417-423 (DOI: 10. 1038/nature02517).
45. Demontis F, Penimon N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell, 2010, 143(5): 813-825(DOI: 10.1016/j .cell.2010.10.007).
46. Schaetzlein S, Kodandaramireddy N R, Ju Z, et al. Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell, 2007, 130(5): 863-877 (DOI: 10.1016/j.cell.2007.08.029).
47. Lundblad V, Blackburn E H. An alternative pathway for yeast telomere maintenance rescues estl- senescence. Cell, 1993, 73(2): 347-360.
48. Lundblad V, Szostak J W. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell, 1989, 57(4): 633-643.
49. D'Adda di Fagagna F, Reaper P M, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature, 2003, 426(6963): 194-198(DOI: 10.1038/nature02118).
50. Wong K K, Maser R S, Bachoo R M, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature, 2003, 421 (6923): 643-648 (DOI: 10.1038/nature01385).
51. Hastie N D, Dempster M, Dunlop M G, et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature, 1990, 346(6287): 866-868(DOI: 10.1038/346866a0).
52. Yu G L, Bradley J D, Attardi L D, et al. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature, 1990, 344(6262): 126-132 (DOI: 10.1038/344126a0).
53. Karlseder J, Smogorzewska A, de Lange T. Senescence induced by altered telomere state, not telomere loss. Science, 2002, 295(5564): 2446-2449(DOI: 10.1126/science.l069523).
54. Nicholls C, Pinto A R, Li H, et al. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component. Proc Natl Acad Sci USA, 2012, 109 (33): 13308-13313 (DOI: 10.1073/pnas. 1206672109).
55. Mahmoud A I, Kocabas F, Muralidhar S A, et al. Meisl regulates postnatal cardiomyocyte cell cycle arrest. Nature, 2013, 497(7448): 249-253(DOI: 10.1038/naturel2054).
56. Kang T W, Yevsa T, Woller N, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature, 2011, 479(7374): 547-551(DOI: 10.1038/naturel0599).
57. Storer M, Mas A, Robert-Moreno A, et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell, 2013, 155(5): 1119-1130(001: 10.1016/j.cell. 2013.10.041).
58. Li H, Xu D, Li J, et al. Transforming growth factor beta suppresses human telomerase reverse transcriptase (hTERT) by Smad3 interactions with c-Myc and the hTERT gene. J Biol Chem, 2006, 281(35): 25588-25600.
59. Li H, Xu D, Toh B, et al. TGF-beta and cancer: is Smad3 a repressor of hTERT gene?. Cell Res, 2006, 16(2): 169-173.
60. Cassar L, Li H, Pinto A R, et al. Bone morphogenetic protein-7 inhibits telomerase activity, telomere maintenance, and cervical tumor growth. Cancer Res, 2008, 68 (22): 9157-9166 (DOI: 10.1158/0008-5472.CAN-08-1323).
61. Katik I, Mackenzie-Kludas C, Nicholls C, et al. Activin inhibits telomerase activity in cancer. Biochem Biophys Res Commun, 2009, 389(4): 668-672(DOI: 10.1016/j.bbrc.2009.09.055).
62. Liu J P, Nicholls C, Chen S M, et al. Strategies of treating cancer by cytokine regulation of chromosome end remodelling. Clin Exp Pharmacol Physiol, 2010, 17 (1): 88-92 (DOI: 10.1111/j. 1440-1681.2009.05251.x).
63. Liu J P, Chen S M, Cong Y S, et al. Regulation of telomerase activity by apparently opposing elements. Ageing Res Rev, 2010, 9(3): 245-256(DOI: 10.1016/j.arT.2010.03.002).
64. Wang Y, Sharpless N, Chang S. pl6 (INK4a) protects against dysfunctional telomere-induced ATR-dependent DNA damage responses. J Clin Invest, 2013, 123(10): 4489-4501 (DOI: 10.1172/JCI69574).
65. Yasaei H, Gilham E, Pickles J C, et al. Carcinogen-specific mutational and epigenetic alterations in INK4A, INK4B and p53 tumour-suppressor genes drive induced senescence bypass in normal diploid mammalian cells. Oncogene, 2013, 32(2): 171-179 (DOI: 10.1038/onc.2012.45).
66. Yoshimoto S, Loo T M, Atarashi K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature, 2013, 499 (7456): 97-101 (DOI: 10.1038/nature12347).
67. Conboy IM, Conboy M J, Wagers A J, et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 2005, 433(7027): 760-764(DOI: 10.1038/nature03260).
68. Villeda S A, Luo J, Mosher K I, et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 2011, 477(7362): 90-94(001: 10.1038/naturel0357).
69. Loffredo F S, Steinhauser M L, Jay S M, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell, 2013, 153(4): 828-839(DOI: 10.1016/j .cell.2013.04.015).
70. Millay D P, CRourke J R, Sutherland L B, et al. Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature, 2013, 499(7458): 301-305(001: 10.1038/naturel2343).
71. Yi P, Park J S, Melton D A. Betatrophin: A hormone that controls pancreatic beta cell proliferation. Cell, 2013, 153(4): 747-758(DOI: 10.1016/j .cell.2013.04.008).
72. Zhang G, Li J, Purkayastha S, et al. Hypothalamic programming of systemic ageing involving DCK-beta, NF-kappaB and GnRH. Nature, 2013, 497(7448): 211-216(DOI: 10.1038/naturel2143).
73. Cota D, Proulx K, Smith K A, et al. Hypothalamic mTOR signaling regulates food intake. Science, 2006, 312 (5775): 927-930 (DOI: 10.1126/science.l 124147).
74. Chaveroux C, Eichner L J, Dufour C R, et al. Molecular and genetic crosstalks between mTOR and ERRalpha are key determinants of rapamycin-induced nonalcoholic fatty liver. Cell Metab, 2013, 17(4): 586-598(DOI: 10.1016/j.cmet.2013.03.003).
75. Wu J J, Liu J, Chen E B, et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep, 2013, 4(5): 913-920 (DOI: 10.1016/j.celrep .2013.07.030).
76. Wullschleger S, Loewith R, Hall M N. TOR signaling in growth and metabolism. Cell, 2006, 124 (3): 471-484 (DOI: 10.1016/j.cell. 2006.01.016).
77. Kaeberlein M, Kennedy B K. Ageing: A midlife longevity drug? Nature, 2009, 460(7253): 331-332(DOI: 10.1038/46033la).
78. Zhang S, Readinger J A, DuBois W, et al. Constitutive reductions in mTOR alter cell size, immune cell development, and antibody production. Blood, 2011, 117 (4): 1228-1238 (DOI: 10.1182/blood-2010-05-287821).
79. Keating R, Hertz T, Wehenkel M, et al. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol, 2013, 14(12): 1266-1276(DOI: 10.1038/ni.2741).
80. Araki K, Turner A P, Shaffer V O, et al. mTOR regulates memory CD8 T-cell differentiation. Nature, 2009, 460(7251): 108-112 (DOI: 10.1038/nature08155).
81. Chang J, Burkett P R, Borges C M, et al. MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling. Proc Natl Acad Sci USA, 2013, 110(6): 2270-2275(001:10.1073/pnas. 1206048110).
82. Delgoffe G M, Pollizzi K N, Waickman A T, et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORCl and mTORC2. Nat Immunol, 2011, 12(4): 295-303(DOI: 10.1038/ni.2005).
83. Gulen M F, Kang Z, Bulek K, et al. The receptor SIGIRR suppresses Thl7 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation. Immunity, 2010, 32(1): 54-66(DOI: 10.1016/j.immuni.2009.12. 003).
84. Liu G, Yang K, Bums S, et al. The SlP(l)-mTOR axis directs the reciprocal differentiation of T(H)1 and T(reg) cells. Nat Immunol, 2010, 11(11): 1047-1056(001: 10.1038/ni.l939).
85. Liu G, Bums S, Huang G, et al. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat Immunol, 2009, 10 (7): 769-777 (DOI: 10.1038/ni.l743).
86. Procaccini C, De Rosa V, Galgani M, et al. An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity, 2010, 33 (6): 929-941 (DOI: 10.1016/j.immuni.2010. 11.024).
87. Cobbold S P, Adams E, Farquhar C A, et al. Infectious tolerance via the consumption of essential amino acids and mTOR signaling. Proc Natl Acad Sci USA, 2009, 106 (29): 12055-12060 (DOI: 10.1073/pnas.0903919106).
88. Weichhart T, Haidinger M, Katholnig K, et al. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood, 2011, 117 (16): 4273-4283 (DOI: 10.1182/blood-2010-09-310888).
89. Vander Haar E, Lee S I, Bandhakavi S, et al. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol, 2007, 9(3): 316-323(DOI: 10.1038/ncbl547).
90. Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulkl. Nat Cell Biol, 2011, 13(2): 132-141(DOI: 10.1038/ncb2152).
91. Nazio F, Strappazzon F, Antonioli M, et al. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol, 2013, 15(4): 406-416(001: 10.1038/ncb2708).
92. Yu L, McPhee C K, Zheng L, et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature, 2010, 465(7300): 942-946(DOI: 10.1038/nature09076).
93. Cang C, Zhou Y, Navarro B, et al. mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state. Cell, 2013, 152(4): 778-790(001: 10.1016/j.cell.2013.01.023).
94. Cunningham J T, Rodgers J T, Arlow D H, et al. mTOR controls mitochondrial oxidative function through a YY1-PGC-1 alpha transcriptional complex. Nature, 2007, 450(7170): 736-740(001: 10.1038/nature06322).
95. Johnson S C, Yanos M E, Kayser E B, et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science, 2013, 342 (6165): 1524-1528 (DOI: 10.1126/science.l244360).
96. Yang H, Rudge D G, Koos J D, et al. mTOR kinase structure, mechanism and regulation. Nature, 2013, 497 (7448): 217-223 (DOI: 10.1038/nature 12122).
97. Yamaguchi H, Calado R T, Ly H, et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med, 2005, 352 (14): 1413-1424 (DOI: 10.1056/NEJMoa042980).
98. Yamaguchi H, Baerlocher G M, Lansdorp P M, et al. Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Blood, 2003, 102(3): 916-918 (DOI: 10.1182/blood-2003-01-0335).
99. Mitchell J R, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature, 1999, 402(6761): 551-555(DOI: 10.1038/990141).
100. Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature, 2001, 413 (6851): 432-435 (DOI: 10.1038/35096585).
101. Heiss N S, Knight S W, Vulliamy T J, et al. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet, 1998, 19(1): 32-38(DOI: 10.1038/ng0598-32).
102. Tsakiri K D, Cronkhite J T, Kuan P J, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci USA, 2007, 104(18): 7552-7557(DOI: 10.1073/pnas.0701009104).
103. Armanios M Y, Chen J J, Cogan J D, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med, 2007, 356(13): 1317-1326(DOI: 10.1056/NEJMoa066157).
104. Armanios M, Chen J L, Chang Y P, et al. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci USA, 2005, 102(44): 15960-15964(DOI: 10.1073/pnas.0508124102).
105. Cao Y, Li H, Mu F T, et al. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J, 2002, 16(1): 96-98(DOI: 10.1096/cj.01-0447).
106. Noureddine H, Gary-Bobo G, Alifano M, et al. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res, 2011, 109(5): 543-553(DOI: 10.1161/CIRCRESAHA. 111.241299).
107. Benetos A, Gardner J P, Zureik M, et al. Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension, 2004, 43(2): 182-185 (DOI: 10.1161/01. HYP.0000113081.42868.f4).
108. Huda N, Tanaka H, Herbert B S, et al. Shared environmental factors associated with telomere length maintenance in elderly male twins. Aging Cell, 2007, 6(5): 709-713(001: 10.111 l/j.1474-9726. 2007.00330.x).
109. Yang Z, Huang X, Jiang H, et al. Short telomeres and prognosis of hypertension in a Chinese population. Hypertension, 2009, 53 (4): 639-645 (DOI: 10.1161/HYPERTENSIONAHA.108.123752).
110. Daniali L, Benetos A, Susser E, et al. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun, 2013, 4: 1597(DOI: 10.1038/ncomms2602).
111. Codd V, Nelson C P, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet, 2013, 45(4): 422-427, 427el-2(DOI: 10.1038/ng.2528).
112. Killela P J, Reitman Z J, Jiao Y, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA, 2013, 110(15): 6021-6026(001:10.1073/ pnas.l303607110).
113. Weischer M, Nordestgaard B G, Cawthon R M, et al. Short telomere length, cancer survival, and cancer risk in 47102 individuals. J Natl Cancer Inst, 2013, 105 (7): 459-468 (DOI: 10.1093/jnci/dj tO 16).
114. Deng Z, Glousker G, Molczan A, et al. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal- Hreidarsson syndrome. Proc Natl Acad Sci USA, 2013, 110(36): E3408-E3416(DOI: 10.1073/pnas. 1300600110).
115. Vannier J B, Sandhu S, Petalcorin M I, et al. RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication. Science, 2013, 342(6155): 239-242(DOI: 10.1126/science.l241779).
116. Gu P, Chang S. Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus. Aging Cell, 2013, 12(6): 1100-1109(DOI: 10.111 l/acel.l2139.
117. Zhang Y, Chen L Y, Han X, et al. Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc Natl Acad Sci USA, 2013, 110(14): 5457-5462 (DOI: 10.1073/pnas. 1217733110).
118. Balk B, Maicher A, Dees M, et al. Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nat Struct Mol Biol, 2013, 20(10): 1199-1205(DOI: 10.1038/nsmb.2662).
119. Cesare A J, Hayashi M T, Crabbe L, et al. The telomere deprotection response is functionally distinct from the genomic DNA damage response. Mol Cell, 2013, 51 (2): 141-155 (DOI: 10.1016/j .molcel.2013.06.006).
120. Cookson W O, Moffatt M F. Bedside to gene and back in idiopathic pulmonary fibrosis. N Engl J Med, 2013, 368 (23): 2228-2230(001:10.1056/ NEJMel304758).
121. Fernandez I E, Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet, 2012, 380 (9842): 680-688 (DOI: 10.1016/SO140-6736(12)61144-1).
122. King T E, Jr Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet, 2011, 378 (9807): 1949-1961 (DOI: 10.1016/S0140- 6736(11)60052-4).
123. Fernandez B A, Fox G, Bhatia R, et al. A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features. Respir Res, 2012, 13: 64 (DOI: 10.1186/1465-9921-13-64).
124. Alder J K, Chen J J, Lancaster L, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci USA, 2008, 105(35): 13051-13056(DOI: 10.1073/pnas.0804280105).
125. Lee J, Reddy R, Barsky L, et al. Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice. Am J Physiol Lung Cell Mol Physiol, 2009, 296 (1): L57-L70 (DOI: 10.1152/ajplung.90411.2008).
126. Savale L, Chaouat A, Bastuji-Garin S, et al. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2009, 179 (7): 566-571 (DOI: 10.1164/rccm.200809- 13980C).
127. Lee J, Sandford A J, Connett J E, et al. The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD). PLoS One, 2012, 7 (4): e35567 (DOI: 10.137 l/journal.pone.0035567).
128. Alder J K, Guo N, Kembou F, et al. Telomere length is a determinant of emphysema susceptibility. Am J Respir Crit Care Med, 2011, 184(8): 904-912(001: 10.1164/rccm.201103-05200C).
129. Amsellem V, Gary-Bobo G, Marcos E, et al. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2011, 184(12): 1358-1366 (DOI: 10.1164/rccm.201105-08020C).
130. Faner R, Rojas M, Macnee W, et al. Abnormal lung aging in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2012, 186(4): 306-313(001: rccm.10.1164/rccm.201202-0282PP).
131. Muller K C, Welker L, Paasch K, et al. Lung fibroblasts fiom patients with emphysema show markers of senescence in vitro. Respir Res, 2006, 7: 32(DOI: 10.1186/1465-9921-7-32).
132. Houben J M, Mercken E M, Ketelslegers H B, et al. Telomere shortening in chronic obstructive pulmonary disease. Respir Med, 2009, 103(2): 230-236(001: 10.1016/j.rmed.2008.09.003).
133. Willis B C, Liebler J M, Luby-Phelps K, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta 1: potential role in idiopathic pulmonary fibrosis. Am J Pathol, 2005, 166(5): 1321-1332.
134. Whyte M K. Genetic factors in idiopathic pulmonary fibrosis: Transforming growth factor-beta implicated at last. Am J Respir Crit Care Med, 2003, 168(4): 410-411(DOI: 10.1164/rccm.2306003).
135. Xaubet A, Marin-Arguedas A, Lario S, et al. Transforming growth factor-beta 1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2003, 168(4): 431-435(DOI: 10.1164/rccm.200210-11650C).
136. Yong S J, Adlakha A, Limper A H. Circulating transforming growth factor-beta(l): A potential marker of disease activity during idiopathic pulmonary fibrosis. Chest, 2001, 120(1 Suppl): 68S-70S.
137. Khalil N, O'Connor R, Gold L I, et al. Biological effects of transforming growth factor-beta(l) in idiopathic pulmonary fibrosis may be regulated by the activation of latent transforming growth factor-beta (1) and the differential expression of transforming growth factor-beta receptors. Chest, 2001, 120(1 Suppl): 48S.
138. Mori M, Kida H, Morishita H, et al. Microsatellite instability in transforming growth factor-beta 1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis. Am J Respir Ceil Mol Biol, 2001, 24(4): 398-404(001: 10.1165/ajrcmb.24.4. 4206).
139. Khalil N, O'Connor R N, Unruh H W, et al. Increased production and immune histochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol, 1991, 5(2): 155-162.
140. Khalil N, O'Connor R, Unruh H, et al. Enhanced expression and immune histochemical distribution of transforming growth factor-beta in idiopathic pulmonary fibrosis. Chest, 1991, 99(3 Suppl): 65S-66S.
141. Budd D C, Holmes A M. Targeting TGFbeta superfamily ligand accessory proteins as novel therapeutics for chronic lung disorders. Pharmacol Ther, 2012, 135 (3): 279-291 (DOI: 10.1016/j. pharmthera.2012.06.001).
142. Pandit K V, Corcoran D, Yousef H, et al. Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2010, 182(2): 220-229(001:10.1164/rccm.200911-16980C).
143. Cassar L, Li H, Jiang F X, et al. TGF-beta induces telomerase- dependent pancreatic tumor cell cycle arrest. Mol Cell Endocrinol, 2010, 320(1-2): 97-105(001: 10.1016/j.mce.2010.02.002).
144. Hu B, Tack D C, Liu T. et al. Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFbeta. Oncogene, 2006, 25(7): 1030-1041.
145. Lacerte A, Korah J, Roy M, et al. Transforming growth factor-beta inhibits telomerase through SMAD3 and E2F transcription factors. Cell Signal, 2008, 20(1): 50-59 (DOI: 10.1016/j.cellsig.2007.08. 012).
146. Aviv A, Aviv H. Reflections on telomeres, growth, aging, and essential hypertension. Hypertension, 1997, 29(5): 1067-1072.
147. Burchell V S, Nelson D E, Sanchez-Martinez A, et al. The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci, 2013, 16(9): 1257-1265(DOI: 10.1038/nn.3489).
148. Hasson S A, Kane L A, Yamano K, et al. High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy. Nature, 2013, 504 (7479): 291-295 (DOI: 10.1038/naturel2748).
149. Okatsu K, Uno M, Koyano F, et al. A dimeric PINK1-containing complex on depolarized mitochondria stimulates Parian recruitment. J Biol Chem, 2013, 288(51): 36372-36384 (DOI: 10.1074/jbc.Ml 13.509653).
150. Sarraf S A, Raman M, Guarani-Pereira V, et al. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature, 2013, 496 (7445): 372-376 (DOI: 10.1038/naturel2043).
151. Muller-Rischart A K, Pilsl A, Beaudette P, et al. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell, 2013, 49(5): 908-921 (DOI: 10.1016/j.molcel.2013.01.036).
152. Ekholm-Reed S, Goldberg M S, Schlossmacher M G, et al. Parkin-dependent degradation of the F-box protein Fbw7beta promotes neuronal survival in response to oxidative stress by stabilizing Mcl-1. Mol Cell Biol, 2013, 33(18): 3627-3643(DOI: 10.1128/MCB.00535-13).
153. Manzanillo P S, Ayres J S, Watson R O, et al. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature, 2013, 501(7468): 512-516(DOI: 10.1038/naturel2566).
154. Allen G F, Toth R, James J, et al. Loss of iron triggers PINKL/PAIKIN-independent mitophagy. EMBO Rep, 2013, 14(12): 1127-1135(DOI: 10.1038/embor.2013.168).
155. Esposito G, Vos M, Vilain S, et al. Aconitase causes iron toxicity in Drosophila pinkl mutants. PLoS Genet, 2013, 9(4): el003478 (DOI: 10.1371/joumal.pgen. 1003478).
156. Hertz N T, Berthet A, Sos M L, et al. A neo-substrate that amplifies catalytic activity of parkinson's-disease-related kinase PINK1. Cell, 2013, 154(4): 737-747(DOI: 10.1016/j.cell.2013.07.030).
157. Yang Y H, Johnson J D. Multi-parameter single-cell kinetic analysis reveals multiple modes of cell death in primary pancreatic beta-cells. J Cell Sci, 2013, 126(Ptl8): 4286-4295(DOI: 10.1242/jcs.133017).
158. Shang L, Hua H, Foo K, et al. Beta cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome. Diabetes, 2013(001:10.2337/ dbl3-0717).
159. Wikstrom J D, Israeli T, Bachar-Wikstrom E, et al. AMPK regulates ER morphology and function in stressed pancreatic beta-cells via phosphorylation of DRP1. Mol Endocrinol, 2013, 27(10): 1706-1723(001: 10.1210/me.2013-1109).
160. Lee Y S, Morinaga H, Kim J J, et al. The fractalkine/CX3CRl system regulates beta cell function and insulin secretion. Cell, 2013, 153(2): 413-425(bOI: 10.1016/j .cell.2013.03.001).
161. Song R, Peng W, Zhang Y, et al. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders. Nature, 2013, 494(7437): 375-379(DOI: 10.1038/naturell834).
162. Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature, 2013, 503(7477): 493-499(DOI: 10.1038/naturel2656).
163. Pearce L R, Atanassova N, Banton M C, et al. KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. Cell, 2013, 155(4): 765-777 (DOI: 10.1016/j.cell. 2013.09.058).
164. Costanzo-Garvey D L, Pfluger P T, Dougherty M K, et al. KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity. Cell Metab, 2009, 10 (5): 366-378 (DOI: 10.1016/j .cmet.2009.09.010).
165. Jonker J W, Suh J M, Atkins A R, et al. A PPARgamma-FGFl axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature, 2012, 485 (7398): 391-394 (DOI: 10.1038/naturel0998).
166. Cipolletta D, Feuerer M, Li A, et al. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature, 2012, 486 (7404): 549-553 (DOI: 10.1038/naturelll32).
167. Satoh T, Kidoya H, Naito H, et al. Critical role of Tribl in differentiation of tissue-resident M2-like macrophages. Nature, 2013, 495(7442): 524-528(DOI: 10.1038/naturell930).
168. Eller K, Kirsch A, Wolf A M, et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes, 2011, 60 (11): 2954-2962 (DOI: 10.2337/dbl 1-0358).
169. Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 2012, 490(7418): 55-60 (DOI: 10.1038/naturel 1450).
170. Cabreiro F, Au C, Leung K Y, et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell, 2013, 153(1): 228-239(DOI: 10.1016/j .cell.2013.02.035).
171. He C, Bassik M C, Moresi V, et al. Exercise-induced BCL2- regulated autophagy is required for muscle glucose homeostasis. Nature, 2012, 481(7382): 511-515(DOI: 10.1038/naturel0758).
172. Rando T A. Stem cells, ageing and the quest for immortality. Nature, 2006, 441(7097): 108D-1086(DOI: 10.1038/nature04958).
173. Johnson S C, Rabinovitch P S, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature, 2013, 493(7432): 338-345(DOI: 10.1038/naturell861).
174. Vaupel J W. Biodemography of human ageing. Nature, 2010, 464(7288): 536-542(DOI: 10.1038/nature08984).