Molecular insights into the premature aging disease progeria

Histochemistry and Cell Biology

Volumn 145, Issue 4, 2016, Pages 401-417

  Vidak, Sandra ^a   Foisner, Roland ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Adult stem cells; Chromatin; Lamins; Nucleoplasmic lamins; Premature aging; Progeria; Senescence; Signaling

Indexed keywords

LAMIN; LAMIN A; LMNA PROTEIN, HUMAN;

ADULT STEM CELL; BIOCHEMISTRY; CHROMATIN; EXTRACELLULAR MATRIX; GENETICS; GENOMIC INSTABILITY; HUMAN; HUTCHINSON GILFORD PROGERIA SYNDROME; MOUSE MODEL; NONHUMAN; PHENOTYPE; PREMATURE AGING; PRIORITY JOURNAL; PROGERIA; REVIEW; SIGNAL TRANSDUCTION; CELL AGING; CELL NUCLEUS; METABOLISM; MUTATION; PATHOLOGY;

AGING, PREMATURE; CELL AGING; CELL NUCLEUS; HUMANS; LAMIN TYPE A; MUTATION; PROGERIA;

EID: 84957573722     PISSN: 09486143     EISSN: 1432119X     Source Type: Journal    
DOI: 10.1007/s00418-016-1411-1     Document Type: Review

References (181)

1. Amendola M, van Steensel B (2014) Mechanisms and dynamics of nuclear lamina–genome interactions. Curr Opin Cell Biol 28:61–68. doi:10.1016/j.ceb.2014.03.003
2. Andres V, Gonzalez JM (2009) Role of A-type lamins in signaling, transcription, and chromatin organization. J Cell Biol 187(7):945–957. doi:10.1083/jcb.200904124
3. Baek JH, Schmidt E, Viceconte N, Strandgren C, Pernold K, Richard TJ, Van Leeuwen FW, Dantuma NP, Damberg P, Hultenby K, Ulfhake B, Mugnaini E, Rozell B, Eriksson M (2015) Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior. Hum Mol Genet 24(5):1305–1321. doi:10.1093/hmg/ddu541
4. Barker AJ, Lanning C, Shandas R (2010) Quantification of hemodynamic wall shear stress in patients with bicuspid aortic valve using phase-contrast MRI. Ann Biomed Eng 38(3):788–800. doi:10.1007/s10439-009-9854-3
5. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7117):337–342. doi:10.1038/nature05354
6. Benson EK, Lee SW, Aaronson SA (2010) Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence. J Cell Sci 123(15):2605–2612. doi:10.1242/jcs.067306
7. Bergo MO, Gavino B, Ross J, Schmidt WK, Hong C, Kendall LV, Mohr A, Meta M, Genant H, Jiang Y, Wisner ER, Van Bruggen N, Carano RA, Michaelis S, Griffey SM, Young SG (2002) Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc Natl Acad Sci USA 99(20):13049–13054. doi:10.1073/pnas.192460799
8. Blasco MA (2005) Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 6(8):611–622. doi:10.1038/nrg1656
9. Brachner A, Foisner R (2011) Evolvement of LEM proteins as chromatin tethers at the nuclear periphery. Biochem Soc Trans 39(6):1735–1741. doi:10.1042/BST20110724
10. Brassard JA, Fekete N, Garnier A, Hoesli CA (2015) Hutchinson–Gilford progeria syndrome as a model for vascular aging. Biogerontology. doi:10.1007/s10522-015-9602-z
11. Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123(3):951–957. doi:10.1172/JCI64125
12. Bridger JM, Kill IR (2004) Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis. Exp Gerontol 39(5):717–724
13. Broers JL, Ramaekers FC, Bonne G, Yaou RB, Hutchison CJ (2006) Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev 86(3):967–1008. doi:10.1152/physrev.00047.2005
14. Bronshtein I, Kepten E, Kanter I, Berezin S, Lindner M, Redwood AB, Mai S, Gonzalo S, Foisner R, Shav-Tal Y, Garini Y (2015) Loss of lamin A function increases chromatin dynamics in the nuclear interior. Nat Commun 6:8044. doi:10.1038/ncomms9044
15. Brunauer R, Kennedy BK (2015) Medicine. Progeria accelerates adult stem cell aging. Science 348(6239):1093–1094. doi:10.1126/science.aac4214
16. Burtner CR, Kennedy BK (2010) Progeria syndromes and ageing: what is the connection? Nat Rev Mol Cell Biol 11(8):567–578. doi:10.1038/nrm2944
17. Buxboim A, Swift J, Irianto J, Spinler KR, Dingal PC, Athirasala A, Kao YR, Cho S, Harada T, Shin JW, Discher DE (2014) Matrix elasticity regulates lamin-A, C phosphorylation and turnover with feedback to actomyosin. Curr Biol 24(16):1909–1917. doi:10.1016/j.cub.2014.07.001
18. Cabanillas R, Cadinanos J, Villameytide JA, Perez M, Longo J, Richard JM, Alvarez R, Duran NS, Illan R, Gonzalez DJ, Lopez-Otin C (2011) Nestor–Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations. Am J Med Genet A 155A(11):2617–2625. doi:10.1002/ajmg.a.34249
19. Campisi J, Andersen JK, Kapahi P, Melov S (2011) Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol 21(6):354–359. doi:10.1016/j.semcancer.2011.09.001
20. Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS (2011a) Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Invest 121(7):2833–2844. doi:10.1172/JCI43578
21. Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, Krainc D, Collins FS (2011b) Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson–Gilford progeria syndrome cells. Sci Transl Med. doi:10.1126/scitranslmed.3002346
22. Capell BC, Erdos MR, Madigan JP, Fiordalisi JJ, Varga R, Conneely KN, Gordon LB, Der CJ, Cox AD, Collins FS (2005) Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci USA 102(36):12879–12884. doi:10.1073/pnas.0506001102
23. Cau P, Navarro C, Harhouri K, Roll P, Sigaudy S, Kaspi E, Perrin S, De Sandre-Giovannoli A, Levy N (2014) Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective. Semin Cell Dev Biol. doi:10.1016/j.semcdb.2014.03.022
24. Caux F, Dubosclard E, Lascols O, Buendia B, Chazouilleres O, Cohen A, Courvalin JC, Laroche L, Capeau J, Vigouroux C, Christin-Maitre S (2003) A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J Clin Endocrinol Metab 88(3):1006–1013. doi:10.1210/jc.2002-021506
25. Cenni V, Capanni C, Columbaro M, Ortolani M, D’Apice MR, Novelli G, Fini M, Marmiroli S, Scarano E, Maraldi NM, Squarzoni S, Prencipe S, Lattanzi G (2011) Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria. Eur J Histochem 55(4):200–205. doi:10.4081/ejh.2011.e36
26. Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J (2003) LMNA mutations in atypical Werner’s syndrome. Lancet 362(9382):440–445. doi:10.1016/S0140-6736(03)14069-X
27. Chen ZJ, Wang WP, Chen YC, Wang JY, Lin WH, Tai LA, Liou GG, Yang CS, Chi YH (2014) Dysregulated interactions between lamin A and SUN1 induce abnormalities in the nuclear envelope and endoplasmic reticulum in progeric laminopathies. J Cell Sci 127(Pt 8):1792–1804. doi:10.1242/jcs.139683
28. Chojnowski A, Ong PF, Wong ES, Lim JS, Mutalif RA, Navasankari R, Dutta B, Yang H, Liow YY, Sze SK, Boudier T, Wright GD, Colman A, Burke B, Stewart CL, Dreesen O (2015) Progerin reduces LAP2α-telomere association in Hutchinson–Gilford progeria. Elife. doi:10.7554/eLife.07759
29. Colige A, Nusgens B, Lapiere CM (1991) Altered response of progeria fibroblasts to epidermal growth factor. J Cell Sci 100(Pt 3):649–655
30. Collado M, Blasco MA, Serrano M (2007) Cellular senescence in cancer and aging. Cell 130(2):223–233. doi:10.1016/j.cell.2007.07.003
31. Columbaro M, Capanni C, Mattioli E, Novelli G, Parnaik VK, Squarzoni S, Maraldi NM, Lattanzi G (2005) Rescue of heterochromatin organization in Hutchinson–Gilford progeria by drug treatment. Cell Mol Life Sci 62(22):2669–2678. doi:10.1007/s00018-005-5318-6
32. Coulombe PA, Ma L, Yamada S, Wawersik M (2001) Intermediate filaments at a glance. J Cell Sci 114(Pt 24):4345–4347
33. Csoka AB, Cao H, Sammak PJ, Constantinescu D, Schatten GP, Hegele RA (2004) Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J Med Genet 41(4):304–308
34. Dahl KN, Scaffidi P, Islam MF, Yodh AG, Wilson KL, Misteli T (2006) Distinct structural and mechanical properties of the nuclear lamina in Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci USA 103(27):10271–10276. doi:10.1073/pnas.0601058103
35. Davies BSJ, Fong LG, Yang SH, Coffinier C, Young SG (2009) The posttranslational processing of prelamin A and disease. Annu Rev Genomics Hum Genet 10:153–174. doi:10.1146/annurev-genom-082908-150150
36. Davies BS, Barnes RH 2nd, Tu Y, Ren S, Andres DA, Spielmann HP, Lammerding J, Wang Y, Young SG, Fong LG (2010) An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Hum Mol Genet 19(13):2682–2694. doi:10.1093/hmg/ddq158
37. de la Rosa J, Freije JMP, Cabanillas R, Osorio FG, Fraga MF, Fernandez-Garcia MS, Rad R, Fanjul V, Ugalde AP, Liang Q, Prosser HM, Bradley A, Cadinanos J, Lopez-Otin C (2013) Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion. Nat Commun. doi:10.1038/Ncomms3268
38. 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. doi:10.1126/science.1084125
39. Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R (2000) Lamina-associated polypeptide 2α binds intranuclear A-type lamins. J Cell Sci 113(Pt 19):3473–3484
40. Dechat T, Shimi T, Adam SA, Rusinol AE, Andres DA, Spielmann HP, Sinensky MS, Goldman RD (2007) Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc Natl Acad Sci USA 104(12):4955–4960. doi:10.1073/pnas.0700854104
41. Dechat T, Adam SA, Goldman RD (2009) Nuclear lamins and chromatin: when structure meets function. Adv Enzyme Regul 49(1):157–166. doi:10.1016/j.advenzreg.2008.12.003
42. Dechat T, Adam SA, Taimen P, Shimi T, Goldman RD (2010a) Nuclear lamins. Cold Spring Harb Perspect Biol 2(11):a000547. doi:10.1101/cshperspect.a000547
43. Dechat T, Gesson K, Foisner R (2010b) Lamina-independent lamins in the nuclear interior serve important functions. Cold Spring Harb Symp Quant Biol 75:533–543. doi:10.1101/sqb.2010.75.018
44. Decker ML, Chavez E, Vulto I, Lansdorp PM (2009) Telomere length in Hutchinson–Gilford Progeria Syndrome. Mech Ageing Dev 130(6):377–383. doi:10.1016/j.mad.2009.03.001
45. Delbarre E, Tramier M, Coppey-Moisan M, Gaillard C, Courvalin JC, Buendia B (2006) The truncated prelamin A in Hutchinson–Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers. Hum Mol Genet 15(7):1113–1122. doi:10.1093/hmg/ddl026
46. di Fagagna FD, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426(6963):194–198. doi:10.1038/nature02118
47. Dittmer T, Misteli T (2011) The lamin protein family. Genome Biol. doi:10.1186/Gb-2011-12-5-222
48. Doh YJ, Kim HK, Jung ED, Choi SH, Kim JG, Kim BW, Lee IK (2009) Novel LMNA gene mutation in a patient with Atypical Werner’s Syndrome. Korean J Intern Med 24(1):68–72. doi:10.3904/kjim.2009.24.1.68
49. Dorner D, Vlcek S, Foeger N, Gajewski A, Makolm C, Gotzmann J, Hutchison CJ, Foisner R (2006) Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. J Cell Biol 173(1):83–93. doi:10.1083/jcb.200511149
50. Doubaj Y, De Sandre-Giovannoli A, Vera EV, Navarro CL, Elalaoui SC, Tajir M, Levy N, Sefiani A (2012) An inherited LMNA gene mutation in atypical progeria syndrome. Am J Med Genet A 158A(11):2881–2887. doi:10.1002/ajmg.a.35557
51. Dreesen O, Stewart CL (2011) Accelerated aging syndromes, are they relevant to normal human aging? Aging (Albany NY) 3(9):889–895
52. Eckersley-Maslin MA, Bergmann JH, Lazar Z, Spector DL (2013) Lamin A/C is expressed in pluripotent mouse embryonic stem cells. Nucleus 4(1):53–60. doi:10.4161/nucl.23384
53. 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. doi:10.1038/nature01629
54. Espada J, Varela I, Flores I, Ugalde AP, Cadinanos J, Pendas AM, Stewart CL, Tryggvason K, Blasco MA, Freije JM, Lopez-Otin C (2008) Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J Cell Biol 181(1):27–35. doi:10.1083/jcb.200801096
55. 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. doi:10.1126/science.1124875
56. Gabriel D, Roedl D, Gordon LB, Djabali K (2015) Sulforaphane enhances progerin clearance in Hutchinson–Gilford progeria fibroblasts. Aging Cell 14(1):78–91. doi:10.1111/acel.12300
57. Garg A, Subramanyam L, Agarwal AK, Simha V, Levine B, D’Apice MR, Novelli G, Crow Y (2009) Atypical progeroid syndrome due to heterozygous missense LMNA mutations. J Clin Endocrinol Metab 94(12):4971–4983. doi:10.1210/jc.2009-0472
58. Gattazzo F, Urciuolo A, Bonaldo P (2014) Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophys Acta 1840(8):2506–2519. doi:10.1016/j.bbagen.2014.01.010
59. Gesson K, Vidak S, Foisner R (2014) Lamina-associated polypeptide (LAP)2α and nucleoplasmic lamins in adult stem cell regulation and disease. Semin Cell Dev Biol 29:116–124. doi:10.1016/j.semcdb.2013.12.009
60. Ghosh S, Hayden MS (2008) New regulators of NF-κB in inflammation. Nat Rev Immunol 8(11):837–848. doi:10.1038/nri2423
61. Ghosh S, Zhou Z (2014) Genetics of aging, progeria and lamin disorders. Curr Opin Genet Dev 26:41–46. doi:10.1016/j.gde.2014.05.003
62. Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, Gruenbaum Y, Khuon S, Mendez M, Varga R, Collins FS (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci USA 101(24):8963–8968. doi:10.1073/pnas.0402943101
63. Gonzalez JM, Navarro-Puche A, Casar B, Crespo P, Andres V (2008) Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. J Cell Biol 183(4):653–666. doi:10.1083/jcb.200805049
64. Gonzalez-Suarez I, Gonzalo S (2010) Nurturing the genome: A-type lamins preserve genomic stability. Nucleus 1(2):129–135. doi:10.4161/nucl.1.2.10797
65. Gonzalo S, Kreienkamp R (2015) DNA repair defects and genome instability in Hutchinson–Gilford progeria syndrome. Curr Opin Cell Biol 34:75–83. doi:10.1016/j.ceb.2015.05.007
66. Gonzalo S, Garcia-Cao M, Fraga MF, Schotta G, Peters AH, Cotter SE, Eguia R, Dean DC, Esteller M, Jenuwein T, Blasco MA (2005) Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol 7(4):420–428. doi:10.1038/ncb1235
67. Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland R, Snyder BD, Fligor B, Bishop WR, Statkevich P, Regen A, Sonis A, Riley S, Ploski C, Correia A, Quinn N, Ullrich NJ, Nazarian A, Liang MG, Huh SY, Schwartzman A, Kieran MW (2012) Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci USA 109(41):16666–16671. doi:10.1073/pnas.1202529109
68. Gordon LB, Rothman FG, Lopez-Otin C, Misteli T (2014) Progeria: A paradigm for translational medicine. Cell 156(3):400–407. doi:10.1016/j.cell.2013.12.028
69. Gotzman J, Foisner R (2006) Lamins and emerin in muscular distrophy. In: Winder SJ (ed) Molecular Mechanisms of Muscular Distrophy. Eureka/Landes Bioscience, New Yoork, pp 142–159
70. Gruenbaum Y, Foisner R (2015) Lamins: nuclear intermediate filament proteins with fundamental functions in nuclear mechanics and genome regulation. Annu Rev Biochem 84:131–164. doi:10.1146/annurev-biochem-060614-034115
71. Halaschek-Wiener J, Brooks-Wilson A (2007) Progeria of stem cells: stem cell exhaustion in Hutchinson–Gilford progeria syndrome. J Gerontol A Biol Sci Med Sci 62(1):3–8
72. Hanker AB, Mitin N, Wilder RS, Henske EP, Tamanoi F, Cox AD, Der CJ (2010) Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling. Oncogene 29(3):380–391. doi:10.1038/onc.2009.336
73. Harten IA, Zahr RS, Lemire JM, Machan JT, Moses MA, Doiron RJ, Curatolo AS, Rothman FG, Wight TN, Toole BP, Gordon LB (2011) Age-dependent loss of MMP-3 in Hutchinson–Gilford progeria syndrome. J Gerontol A Biol Sci Med Sci 66(11):1201–1207. doi:10.1093/gerona/glr137
74. Hernandez L, Roux KJ, Wong ES, Mounkes LC, Mutalif R, Navasankari R, Rai B, Cool S, Jeong JW, Wang H, Lee HS, Kozlov S, Grunert M, Keeble T, Jones CM, Meta MD, Young SG, Daar IO, Burke B, Perantoni AO, Stewart CL (2010) Functional coupling between the extracellular matrix and nuclear lamina by Wnt signaling in progeria. Dev Cell 19(3):413–425. doi:10.1016/j.devcel.2010.08.013
75. Herrmann H, Bar H, Kreplak L, Strelkov SV, Aebi U (2007) Intermediate filaments: from cell architecture to nanomechanics. Nat Rev Mol Cell Biol 8(7):562–573. doi:10.1038/nrm2197
76. Ho CY, Lammerding J (2012) Lamins at a glance. J Cell Sci 125(9):2087–2093. doi:10.1242/Jcs.087288
77. Hoeijmakers JH (2009) DNA damage, aging, and cancer. N Engl J Med 361(15):1475–1485. doi:10.1056/NEJMra0804615
78. Hori K, Sen A, Artavanis-Tsakonas S (2013) Notch signaling at a glance. J Cell Sci 126(Pt 10):2135–2140. doi:10.1242/jcs.127308
79. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425(6954):191–196. doi:10.1038/nature01960
80. Humphrey JD, Dufresne ER, Schwartz MA (2014) Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol 15(12):802–812. doi:10.1038/nrm3896
81. Ivorra C, Kubicek M, Gonzalez JM, Sanz-Gonzalez SM, Alvarez-Barrientos A, O’Connor JE, Burke B, Andres V (2006) A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev 20(6):747 vol 20, p 307
82. Jacob KN, Baptista F, dos Santos HG, Oshima J, Agarwal AK, Garg A (2005) Phenotypic heterogeneity in body fat distribution in patients with atypical Werner’s Syndrome due to heterozygous Arg133Leu lamin A/C mutation. J Clin Endocrinol Metab 90(12):6699–6706. doi:10.1210/jc.2005-0939
83. Johnson BR, Nitta RT, Frock RL, Mounkes L, Barbie DA, Stewart CL, Harlow E, Kennedy BK (2004) A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci USA 101(26):9677–9682. doi:10.1073/pnas.0403250101
84. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493(7432):338–345. doi:10.1038/nature11861
85. Jung CH, Ro SH, Cao J, Otto NM, Kim DH (2010) mTOR regulation of autophagy. FEBS Lett 584(7):1287–1295. doi:10.1016/j.febslet.2010.01.017
86. Kane MS, Lindsay ME, Judge DP, Barrowman J, Ap Rhys C, Simonson L, Dietz HC, Michaelis S (2013) LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset. Am J Med Genet A 161A(7):1599–1611. doi:10.1002/ajmg.a.35971
87. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell 136(1):62–74. doi:10.1016/j.cell.2008.10.052
88. Kieran MW, Gordon L, Kleinman M (2007) New approaches to progeria. Pediatrics 120(4):834–841. doi:10.1542/peds.2007-1356
89. Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS, Janssen H, Amendola M, Nolen LD, Bickmore WA, van Steensel B (2013) Single-cell dynamics of genome-nuclear lamina interactions. Cell 153(1):178–192. doi:10.1016/j.cell.2013.02.028
90. Kirschner J, Brune T, Wehnert M, Denecke J, Wasner C, Feuer A, Marquardt T, Ketelsen UP, Wieacker P, Bonnemann CG, Korinthenberg R (2005) p. S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria. Ann Neurol 57(1):148–151. doi:10.1002/ana.20359
91. Kolb T, Maass K, Hergt M, Aebi U, Herrmann H (2011) Lamin A and lamin C form homodimers and coexist in higher complex forms both in the nucleoplasmic fraction and in the lamina of cultured human cells. Nucleus 2(5):425–433. doi:10.4161/nucl.2.5.17765
92. Korfali N, Wilkie GS, Swanson SK, Srsen V, de Las Heras J, Batrakou DG, Malik P, Zuleger N, Kerr AR, Florens L, Schirmer EC (2012) The nuclear envelope proteome differs notably between tissues. Nucleus 3(6):552–564. doi:10.4161/nucl.22257
93. Kubben N, Voncken JW, Demmers J, Calis C, van Almen G, Pinto Y, Misteli T (2010a) Identification of differential protein interactors of lamin A and progerin. Nucleus 1(6):513–525. doi:10.4161/nucl.1.6.13512
94. Kubben N, Voncken JW, Misteli T (2010b) Mapping of protein- and chromatin-interactions at the nuclear lamina. Nucleus 1(6):460–471. doi:10.4161/nucl.1.6.13513
95. Kubben N, Adriaens M, Meuleman W, Voncken JW, van Steensel B, Misteli T (2012) Mapping of lamin A- and progerin-interacting genome regions. Chromosoma 121(5):447–464. doi:10.1007/s00412-012-0376-7
96. Kubben N, Brimacombe KR, Donegan M, Li Z, Misteli T (2015) A high-content imaging-based screening pipeline for the systematic identification of anti-progeroid compounds. Methods. doi:10.1016/j.ymeth.2015.08.024
97. 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. doi:10.1038/nrm2161
98. Lavasani M, Robinson AR, Lu A, Song M, Feduska JM, Ahani B, Tilstra JS, Feldman CH, Robbins PD, Niedernhofer LJ, Huard J (2012) Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 3:608. doi:10.1038/ncomms1611
99. Lavu S, Boss O, Elliott PJ, Lambert PD (2008) Sirtuins–novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov 7(10):841–853. doi:10.1038/nrd2665
100. Liu BH, Wang JM, Chan KM, Tjia WM, Deng W, Guan XY, Huang JD, Li KM, Chau PY, Chen DJ, Pei DQ, Pendas AM, Cadinanos J, Lopez-Otin C, Tse HF, Hutchison C, Chen JJ, Cao YH, Cheah KSE, Tryggvason K, Zhou ZJ (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11(7):780–785. doi:10.1038/nm1266
101. Liu B, Ghosh S, Yang X, Zheng H, Liu X, Wang Z, Jin G, Zheng B, Kennedy BK, Suh Y, Kaeberlein M, Tryggvason K, Zhou Z (2012) Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab 16(6):738–750. doi:10.1016/j.cmet.2012.11.007
102. 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. doi:10.1038/ncomms2885
103. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217. doi:10.1016/j.cell.2013.05.039
104. Lund E, Oldenburg AR, Delbarre E, Freberg CT, Duband-Goulet I, Eskeland R, Buendia B, Collas P (2013) Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes. Genome Res 23(10):1580–1589. doi:10.1101/gr.159400.113
105. Lund EG, Duband-Goulet I, Oldenburg A, Buendia B, Collas P (2015) Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin. Nucleus 6(1):30–39. doi:10.4161/19491034.2014.990855
106. Madeo F, Tavernarakis N, Kroemer G (2010) Can autophagy promote longevity? Nat Cell Biol 12(9):842–846. doi:10.1038/ncb0910-842
107. Manju K, Muralikrishna B, Parnaik VK (2006) Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. J Cell Sci 119(13):2704–2714. doi:10.1242/jcs.03009
108. Maquart FX, Bellon G, Gillery P, Borel JP, Labeille B, Risbourg B, Denoeux JP (1988) Increased secretion of fibronectin and collagen by progeria (Hutchinson–Gilford) fibroblasts. Eur J Pediatr 147(4):442
109. Margalit A, Brachner A, Gotzmann J, Foisner R, Gruenbaum Y (2007) Barrier-to-autointegration factor—a BAFfling little protein. Trends Cell Biol 17(4):202–208
110. Marji J, O’Donoghue SI, McClintock D, Satagopam VP, Schneider R, Ratner D, Worman HJ, Gordon LB, Djabali K (2010) Defective lamin A-Rb signaling in Hutchinson–Gilford progeria syndrome and reversal by farnesyltransferase inhibition. PLoS ONE 5(6):e11132. doi:10.1371/journal.pone.0011132
111. Markiewicz E, Dechat T, Foisner R, Quinlan RA, Hutchison CJ (2002) Lamin A/C binding protein LAP2α is required for nuclear anchorage of retinoblastoma protein. Mol Biol Cell 13(12):4401–4413. doi:10.1091/mbc.E02-07-0450
112. McClintock D, Ratner D, Lokuge M, Owens DM, Gordon LB, Collins FS, Djabali K (2007) The mutant form of Lamin A that causes Hutchinson–Gilford progeria is a biomarker of cellular aging in human skin. PLoS ONE. doi:10.1371/journal.pone.0001269
113. McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K (2013) Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson–Gilford progeria syndrome. Genome Res 23(2):260–269. doi:10.1101/gr.138032.112
114. McPherson E, Turner L, Zador I, Reynolds K, Macgregor D, Giampietro PF (2009) Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation. Am J Med Genet A 149A(4):567–572. doi:10.1002/ajmg.a.32627
115. Meshorer E, Gruenbaum Y (2009) NURD keeps chromatin young. Nat Cell Biol 11(10):1176–1177. doi:10.1038/ncb1009-1176
116. Meuleman W, Peric-Hupkes D, Kind J, Beaudry JB, Pagie L, Kellis M, Reinders M, Wessels L, van Steensel B (2013) Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence. Genome Res 23(2):270–280. doi:10.1101/gr.141028.112
117. Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, Mandal PK, Vera E, Shim JW, Kriks S, Taldone T, Fusaki N, Tomishima MJ, Krainc D, Milner TA, Rossi DJ, Studer L (2013) Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13(6):691–705. doi:10.1016/j.stem.2013.11.006
118. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang HY, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450(7170):712–716. doi:10.1038/nature06261
119. Moir RD, Yoon M, Khuon S, Goldman RD (2000) Nuclear lamins A and B1: different pathways of assembly during nuclear envelope formation in living cells. J Cell Biol 151(6):1155–1168
120. Moisan E, Girard D (2006) Cell surface expression of intermediate filament proteins vimentin and lamin B1 in human neutrophil spontaneous apoptosis. J Leukoc Biol 79(3):489–498. doi:10.1189/jlb.0405190
121. Mory PB, Crispim F, Kasamatsu T, Gabbay MAL, Dib SA, Moises RS (2008) Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T101 mutation. Arq Bras Endocrinol Metabol 52(8):1252–1256
122. 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. doi:10.1038/nature01631
123. Muchir A, Worman HJ (2010) Signaling defects and the nuclear envelope in progeria. Dev Cell 19(3):355–356. doi:10.1016/j.devcel.2010.08.019
124. Musich PR, Zou Y (2011) DNA-damage accumulation and replicative arrest in Hutchinson–Gilford progeria syndrome. Biochem Soc Trans 39:1764–1769. doi:10.1042/Bst20110687
125. Naetar N, Korbei B, Kozlov S, Kerenyi MA, Dorner D, Kral R, Gotic I, Fuchs P, Cohen TV, Bittner R, Stewart CL, Foisner R (2008) Loss of nucleoplasmic LAP2α—lamin A complexes causes erythroid and epidermal progenitor hyperproliferation. Nat Cell Biol 10(11):1341–1348. doi:10.1038/ncb1793
126. Navarro CL, Cadinanos J, Sandre-Giovannoli AD, Bernard R, Courrier S, Boccaccio I, Boyer A, Kleijer WJ, Wagner A, Giuliano F, Beemer FA, Freije JM, Cau P, Hennekam RCM, Lopez-Otin C, Badens C, Levy N (2005) Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors. Hum Mol Genet 14(11):1503–1513. doi:10.1093/hmg/ddi159
127. Navarro CL, Cau P, Levy N (2006) Molecular bases of progeroid syndromes. Hum Mol Genet 15(2):R151–R161. doi:10.1093/hmg/ddl214
128. Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22(17):R741–R752. doi:10.1016/j.cub.2012.07.024
129. Nitta RT, Smith CL, Kennedy BK (2007) Evidence that proteasome-dependent degradation of the retinoblastoma protein in cells lacking A-type lamins occurs independently of gankyrin and MDM2. PLoS ONE. doi:10.1371/journal.pone.0000963
130. Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, Gerhard-Herman M, Machan JT, Kutys R, Virmani R, Collins FS, Wight TN, Nabel EG, Gordon LB (2010) Cardiovascular pathology in Hutchinson–Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol 30(11):2301–2309. doi:10.1161/ATVBAHA.110.209460
131. Osmanagic-Myers S, Dechat T, Foisner R (2015) Lamins at the crossroads of mechanosignaling. Genes Dev 29(3):225–237. doi:10.1101/gad.255968.114
132. Osorio FG, Navarro CL, Cadinanos J, Lopez-Mejia IC, Quiros PM, Bartoli C, Rivera J, Tazi J, Guzman G, Varela I, Depetris D, de Carlos F, Cobo J, Andres V, De Sandre-Giovannoli A, Freije JM, Levy N, Lopez-Otin C (2011) Splicing-directed therapy in a new mouse model of human accelerated aging. Sci Transl Med 3(106):106ra107. doi:10.1126/scitranslmed.3002847
133. Osorio FG, Lopez-Otin C, Freije JM (2012) NF-kB in premature aging. Aging (Albany NY) 4(11):726–727
134. Pegoraro G, Kubben N, Wickert U, Gohler H, Hoffmann K, Misteli T (2009) Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol 11(10):1261–1267. doi:10.1038/ncb1971
135. Pekovic V, Harborth J, Broers JL, Ramaekers FC, van Engelen B, Lammens M, von Zglinicki T, Foisner R, Hutchison C, Markiewicz E (2007) Nucleoplasmic LAP2α—lamin A complexes are required to maintain a proliferative state in human fibroblasts. J Cell Biol 176(2):163–172. doi:10.1083/jcb.200606139
136. Pellegrini C, Columbaro M, Capanni C, D’Apice MR, Cavallo C, Murdocca M, Lattanzi G, Squarzoni S (2015) All-trans retinoic acid and rapamycin normalize Hutchinson–Gilford progeria fibroblast phenotype. Oncotarget 6(30):29914–29928. doi:10.18632/oncotarget.4939
137. 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. doi:10.1038/ng871
138. Pereira S, Bourgeois P, Navarro C, Esteves-Vieira V, Cau P, De Sandre-Giovannoli A, Levy N (2008) HGPS and related premature aging disorders: from genomic identification to the first therapeutic approaches. Mech Ageing Dev 129(7–8):449–459. doi:10.1016/j.mad.2008.04.003
139. Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, Brugman W, Graf S, Flicek P, Kerkhoven RM, van Lohuizen M, Reinders M, Wessels L, van Steensel B (2010) Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell 38(4):603–613. doi:10.1016/j.molcel.2010.03.016
140. Philip JT, Dahl KN (2008) Nuclear mechanotransduction: response of the lamina to extracellular stress with implications in aging. J Biomech 41(15):3164–3170. doi:10.1016/j.jbiomech.2008.08.024
141. Prokocimer M, Barkan R, Gruenbaum Y (2013) Hutchinson–Gilford progeria syndrome through the lens of transcription. Aging Cell 12(4):533–543. doi:10.1111/acel.12070
142. Renard D, Fourcade G, Milhaud D, Bessis D, Esteves-Vieira V, Boyer A, Roll P, Bourgeois P, Levy N, De Sandre-Giovannoli A (2009) Novel LMNA mutation in atypical Werner syndrome presenting with ischemic disease. Stroke 40(2):e11–e14. doi:10.1161/STROKEAHA.108.531780
143. Richards SA, Muter J, Ritchie P, Lattanzi G, Hutchison CJ (2011) The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Hum Mol Genet 20(20):3997–4004. doi:10.1093/hmg/ddr327
144. Ronningen T, Shah A, Oldenburg AR, Vekterud K, Delbarre E, Moskaug JO, Collas P (2015) Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. Genome Res 25(12):1825–1835. doi:10.1101/gr.193748.115
145. Rosengardten Y, McKenna T, Grochova D, Eriksson M (2011) Stem cell depletion in Hutchinson–Gilford progeria syndrome. Aging Cell 10(6):1011–1020. doi:10.1111/j.1474-9726.2011.00743.x
146. Rusinol AE, Sinensky MS (2006) Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J Cell Sci 119(Pt 16):3265–3272. doi:10.1242/jcs.03156
147. Sagelius H, Rosengardten Y, Hanif M, Erdos MR, Rozell B, Collins FS, Eriksson M (2008) Targeted transgenic expression of the mutation causing Hutchinson–Gilford progeria syndrome leads to proliferative and degenerative epidermal disease. J Cell Sci 121(Pt 7):969–978. doi:10.1242/jcs.022913
148. Sahin E, Depinho RA (2010) Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 464(7288):520–528. doi:10.1038/nature08982
149. Scaffidi P, Misteli T (2005) (R)eversal of the cellular phenotype in the premature aging disease Hutchinson–Gilford progeria syndrome. Nat Med 11(4):440–445. doi:10.1038/nm1204
150. Scaffidi P, Misteli T (2006) Lamin A-dependent nuclear defects in human aging. Science 312(5776):1059–1063. doi:10.1126/science.1127168
151. Scaffidi P, Misteli T (2008) Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol 10(4):452–459. doi:10.1038/ncb1708
152. Schmidt E, Nilsson O, Koskela A, Tuukkanen J, Ohlsson C, Rozell B, Eriksson M (2012) Expression of the Hutchinson–Gilford progeria mutation during osteoblast development results in loss of osteocytes, irregular mineralization, and poor biomechanical properties. J Biol Chem 287(40):33512–33522. doi:10.1074/jbc.M112.366450
153. Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T, Goldman RD (2008) The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev 22(24):3409–3421. doi:10.1101/gad.1735208
154. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 103(23):8703–8708. doi:10.1073/pnas.0602569103
155. Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M, Cohen TV, Devys D, Foisner R, Peichl L, Herrmann H, Blum H, Engelkamp D, Stewart CL, Leonhardt H, Joffe B (2013) LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152(3):584–598. doi:10.1016/j.cell.2013.01.009
156. Song M, San H, Anderson SA, Cannon RO 3rd, Orlic D (2014) Shear stress-induced mechanotransduction protein deregulation and vasculopathy in a mouse model of progeria. Stem Cell Res Ther 5(2):41. doi:10.1186/scrt429
157. Stehbens WE, Wakefield SJ, Gilbert-Barness E, Olson RE, Ackerman J (1999) Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc Pathol 8(1):29–39
158. Strandgren C, Nasser HA, McKenna T, Koskela A, Tuukkanen J, Ohlsson C, Rozell B, Eriksson M (2015) Transgene silencing of the Hutchinson–Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects. FASEB J 29(8):3193–3205. doi:10.1096/fj.14-269217
159. Swift J, Harada T, Buxboim A, Shin JW, Tang HY, Speicher DW, Discher DE (2013) Label-free mass spectrometry exploits dozens of detected peptides to quantify lamins in wildtype and knockdown cells. Nucleus 4(6):450–459. doi:10.4161/nucl.27413
160. Tanida I, Ueno T, Kominami E (2008) LC3 and autophagy. Methods Mol Biol 445:77–88. doi:10.1007/978-1-59745-157-4_4
161. 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-κB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest 122(7):2601–2612. doi:10.1172/JCI45785
162. Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL, Miner JH, Young SG, Fong LG (2005) Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc Natl Acad Sci USA 102(36):12873–12878. doi:10.1073/pnas.0505767102
163. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429(6990):417–423. doi:10.1038/nature02517
164. Varela I, Cadinanos J, Pendas AM, Gutierrez-Fernandez A, Folgueras AR, Sanchez LM, Zhou Z, Rodriguez FJ, Stewart CL, Vega JA, Tryggvason K, Freije JM, Lopez-Otin C (2005) Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437(7058):564–568. doi:10.1038/nature04019
165. Varela I, Pereira S, Ugalde AP, Navarro CL, Suarez MF, Cau P, Cadinanos J, Osorio FG, Foray N, Cobo J, de Carlos F, Levy N, Freije JMP, Lopez-Otin C (2008) Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med 14(7):767–772. doi:10.1038/nm1786
166. 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 USA 103(9):3250–3255. doi:10.1073/pnas.0600012103
167. Verstraeten VLRM, Broers JLV, Ramaekers FCS, van Steensel MAM (2007) The nuclear envelope, a key structure in cellular integrity and gene expression. Curr Med Chem 14(11):1231–1248
168. Verstraeten VL, Ji JY, Cummings KS, Lee RT, Lammerding J (2008) Increased mechanosensitivity and nuclear stiffness in Hutchinson–Gilford progeria cells: effects of farnesyltransferase inhibitors. Aging Cell 7(3):383–393. doi:10.1111/j.1474-9726.2008.00382.x
169. Vidak S, Kubben N, Dechat T, Foisner R (2015) Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins. Genes Dev 29(19):2022–2036. doi:10.1101/gad.263939.115
170. Wenzel V, Roedl D, Gabriel D, Gordon LB, Herlyn M, Schneider R, Ring J, Djabali K (2012) Naive adult stem cells from patients with Hutchinson–Gilford progeria syndrome express low levels of progerin in vivo. Biol Open 1(6):516–526. doi:10.1242/bio.20121149
171. Wilson KL, Foisner R (2010) Lamin-binding proteins. Cold Spring Harb Perspect Biol 2(4):a000554. doi:10.1101/cshperspect.a000554
172. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 431(7004):107. doi:10.1038/nature02941(vol 430, p 686, 2004)
173. Worman HJ (2012) Nuclear lamins and laminopathies. J Pathol 226(2):316–325. doi:10.1002/path.2999
174. Worman HJ, Schirmer EC (2015) Nuclear membrane diversity: underlying tissue-specific pathologies in disease? Curr Opin Cell Biol 34:101–112. doi:10.1016/j.ceb.2015.06.003
175. 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 USA 102(29):10291–10296. doi:10.1073/pnas.0504641102
176. Yang SH, Andres DA, Spielmann HP, Young SG, Fong LG (2008) Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated. J Clin Invest 118(10):3291–3300. doi:10.1172/JCI35876
177. Yang KE, Kwon J, Rhim JH, Choi JS, Kim SI, Lee SH, Park J, Jang IS (2011a) Differential expression of extracellular matrix proteins in senescent and young human fibroblasts: a comparative proteomics and microarray study. Mol Cells 32(1):99–106. doi:10.1007/s10059-011-0064-0
178. Yang SH, Chang SY, Ren S, Wang Y, Andres DA, Spielmann HP, Fong LG, Young SG (2011b) Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin. Hum Mol Genet 20(3):436–444. doi:10.1093/hmg/ddq490
179. Young SG, Fong LG, Michaelis S (2005) Prelamin A, Zmpste24, misshapen cell nuclei, and progeria–new evidence suggesting that protein farnesylation could be important for disease pathogenesis. J Lipid Res 46(12):2531–2558. doi:10.1194/jlr.R500011-JLR200
180. Zhang J, Lian Q, Zhu G, Zhou F, Sui L, Tan C, Mutalif RA, Navasankari R, Zhang Y, Tse HF, Stewart CL, Colman A (2011) A human iPSC model of Hutchinson–Gilford progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell 8(1):31–45. doi:10.1016/j.stem.2010.12.002
181. Zhang S, Schones DE, Malicet C, Rochman M, Zhou M, Foisner R, Bustin M (2013) High mobility group protein N5 (HMGN5) and lamina-associated polypeptide 2α (LAP2α) interact and reciprocally affect their genome-wide chromatin organization. J Biol Chem 288(25):18104–18109. doi:10.1074/jbc.C113.469544