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The Nuclear Envelope in Ageing and Progeria

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Biochemistry and Cell Biology of Ageing: Part III Biomedical Science

Part of the book series: Subcellular Biochemistry ((SCBI,volume 102))

Abstract

Development from embryo to adult, organismal homeostasis and ageing are consecutive processes that rely on several functions of the nuclear envelope (NE). The NE compartmentalises the eukaryotic cells and provides physical stability to the genetic material in the nucleus. It provides spatiotemporal regulation of gene expression by controlling nuclear import and hence access of transcription factors to target genes as well as organisation of the genome into open and closed compartments. In addition, positioning of chromatin relative to the NE is important for DNA replication and repair and thereby also for genome stability. We discuss here the relevance of the NE in two classes of age-related human diseases. Firstly, we focus on the progeria syndromes Hutchinson–Gilford (HGPS) and Nestor–Guillermo (NGPS), which are caused by mutations in the LMNA and BANF1 genes, respectively. Both genes encode ubiquitously expressed components of the nuclear lamina that underlines the nuclear membranes. HGPS and NGPS patients manifest symptoms of accelerated ageing and cells from affected individuals show similar defects as cells from healthy old donors, including signs of increased DNA damage and epigenetic alternations. Secondly, we describe how several age-related neurodegenerative diseases, such as amyotrophic lateral sclerosis and Huntington’s disease, are related with defects in nucleocytoplasmic transport. A common feature of this class of diseases is the accumulation of nuclear pore proteins and other transport factors in inclusions. Importantly, genetic manipulations of the nucleocytoplasmic transport machinery can alleviate disease-related phenotypes in cell and animal models, paving the way for potential therapeutic interventions.

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References

  • Agarwal AK, Fryns JP, Auchus RJ, Garg A (2003) Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet 12(16):1995–2001. https://doi.org/10.1093/hmg/ddg213

    Article  Google Scholar 

  • Barton LJ, Soshnev AA, Geyer PK (2015) Networking in the nucleus: a spotlight on LEM-domain proteins. Curr Opin Cell Biol 34:1–8. https://doi.org/10.1016/j.ceb.2015.03.005

    Article  Google Scholar 

  • Beyret E, Liao HK, Yamamoto M, Hernandez-Benitez R, Fu Y, Erikson G, Reddy P, Izpisua Belmonte JC (2019) Single-dose CRISPR-Cas9 therapy extends lifespan of mice with Hutchinson-Gilford progeria syndrome. Nat Med 25(3):419–422. https://doi.org/10.1038/s41591-019-0343-4

    Article  Google Scholar 

  • Binai NA, Bisschops MM, van Breukelen B, Mohammed S, Loeff L, Pronk JT, Heck AJ, Daran-Lapujade P, Slijper M (2014) Proteome adaptation of Saccharomyces cerevisiae to severe calorie restriction in Retentostat cultures. J Proteome Res 13(8):3542–3553. https://doi.org/10.1021/pr5003388

    Article  Google Scholar 

  • Blondel S, Egesipe AL, Picardi P, Jaskowiak AL, Notarnicola M, Ragot J, Tournois J, Le Corf A, Brinon B, Poydenot P, Georges P, Navarro C, Pitrez PR, Ferreira L, Bollot G, Bauvais C, Laustriat D, Mejat A, De Sandre-Giovannoli A, Levy N, Bifulco M, Peschanski M, Nissan X (2016) Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation. Cell Death Dis 7:e2105. https://doi.org/10.1038/cddis.2015.374

    Article  Google Scholar 

  • Boeynaems S, Bogaert E, Michiels E, Gijselinck I, Sieben A, Jovicic A, De Baets G, Scheveneels W, Steyaert J, Cuijt I, Verstrepen KJ, Callaerts P, Rousseau F, Schymkowitz J, Cruts M, Van Broeckhoven C, Van Damme P, Gitler AD, Robberecht W, Van Den Bosch L (2016) Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD. Sci Rep 6:20877. https://doi.org/10.1038/srep20877

    Article  Google Scholar 

  • Butin-Israeli V, Adam SA, Jain N, Otte GL, Neems D, Wiesmuller L, Berger SL, Goldman RD (2015) Role of Lamin b1 in chromatin instability. Mol Cell Biol 35(5):884–898. https://doi.org/10.1128/MCB.01145-14

    Article  Google Scholar 

  • 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. https://doi.org/10.1002/ajmg.a.34249

    Article  Google Scholar 

  • Cabianca DS, Munoz-Jimenez C, Kalck V, Gaidatzis D, Padeken J, Seeber A, Askjaer P, Gasser SM (2019) Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei. Nature 569(7758):734–739. https://doi.org/10.1038/s41586-019-1243-y

    Article  Google Scholar 

  • Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS (2011) Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Invest 121(7):2833–2844. https://doi.org/10.1172/JCI43578

    Article  Google Scholar 

  • Chang W, Wang Y, Luxton GWG, Ostlund C, Worman HJ, Gundersen GG (2019) Imbalanced nucleocytoskeletal connections create common polarity defects in progeria and physiological aging. Proc Natl Acad Sci U S A 116(9):3578–3583. https://doi.org/10.1073/pnas.1809683116

    Article  Google Scholar 

  • Cho KI, Searle K, Webb M, Yi H, Ferreira PA (2012) Ranbp2 haploinsufficiency mediates distinct cellular and biochemical phenotypes in brain and retinal dopaminergic and glia cells elicited by the Parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell Mol Life Sci 69(20):3511–3527. https://doi.org/10.1007/s00018-012-1071-9

    Article  Google Scholar 

  • Chou CC, Zhang Y, Umoh ME, Vaughan SW, Lorenzini I, Liu F, Sayegh M, Donlin-Asp PG, Chen YH, Duong DM, Seyfried NT, Powers MA, Kukar T, Hales CM, Gearing M, Cairns NJ, Boylan KB, Dickson DW, Rademakers R, Zhang YJ, Petrucelli L, Sattler R, Zarnescu DC, Glass JD, Rossoll W (2018) TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD. Nat Neurosci 21(2):228–239. https://doi.org/10.1038/s41593-017-0047-3

    Article  Google Scholar 

  • Cobb AM, Larrieu D, Warren DT, Liu Y, Srivastava S, Smith AJO, Bowater RP, Jackson SP, Shanahan CM (2016) Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient. Aging Cell 15(6):1039–1050. https://doi.org/10.1111/acel.12506

    Article  Google Scholar 

  • Coyne AN, Baskerville V, Zaepfel BL, Dickson DW, Rigo F, Bennett F, Lusk CP, Rothstein JD (2021) Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS. Sci Transl Med 13(604). https://doi.org/10.1126/scitranslmed.abe1923

  • Cunningham KM, Maulding K, Ruan K, Senturk M, Grima JC, Sung H, Zuo Z, Song H, Gao J, Dubey S, Rothstein JD, Zhang K, Bellen HJ, Lloyd TE (2020) TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS. elife 9. https://doi.org/10.7554/eLife.59419

  • Cutler AA, Dammer EB, Doung DM, Seyfried NT, Corbett AH, Pavlath GK (2017) Biochemical isolation of myonuclei employed to define changes to the myonuclear proteome that occur with aging. Aging Cell 16(4):738–749. https://doi.org/10.1111/acel.12604

    Article  Google Scholar 

  • D’Angelo MA, Raices M, Panowski SH, Hetzer MW (2009) Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells. Cell 136(2):284–295. https://doi.org/10.1016/j.cell.2008.11.037

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Deolal P, Mishra K (2021) Regulation of diverse nuclear shapes: pathways working independently, together. Commun Integr Biol 14(1):158–175. https://doi.org/10.1080/19420889.2021.1939942

    Article  Google Scholar 

  • Dey G, Baum B (2021) Nuclear envelope remodelling during mitosis. Curr Opin Cell Biol 70:67–74. https://doi.org/10.1016/j.ceb.2020.12.004

    Article  Google Scholar 

  • Eftekharzadeh B, Daigle JG, Kapinos LE, Coyne A, Schiantarelli J, Carlomagno Y, Cook C, Miller SJ, Dujardin S, Amaral AS, Grima JC, Bennett RE, Tepper K, DeTure M, Vanderburg CR, Corjuc BT, DeVos SL, Gonzalez JA, Chew J, Vidensky S, Gage FH, Mertens J, Troncoso J, Mandelkow E, Salvatella X, Lim RYH, Petrucelli L, Wegmann S, Rothstein JD, Hyman BT (2018) Tau protein disrupts nucleocytoplasmic transport in Alzheimer’s disease. Neuron 99:925–940.e927. https://doi.org/10.1016/j.neuron.2018.07.039

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S, Lee KH, Badders N, Valentine M, Miller BL, Wong PC, Petrucelli L, Kim HJ, Gao FB, Taylor JP (2015) GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525(7567):129–133. https://doi.org/10.1038/nature14974

    Article  Google Scholar 

  • Freund A, Laberge RM, Demaria M, Campisi J (2012) Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 23(11):2066–2075. https://doi.org/10.1091/mbc.E11-10-0884

    Article  Google Scholar 

  • Gabriel D, Roedl D, Gordon LB, Djabali K (2015) Sulforaphane enhances progerin clearance in Hutchinson-Gilford progeria fibroblasts. Aging Cell 14(1):78–91. https://doi.org/10.1111/acel.12300

    Article  Google Scholar 

  • Gasset-Rosa F, Chillon-Marinas C, Goginashvili A, Atwal RS, Artates JW, Tabet R, Wheeler VC, Bang AG, Cleveland DW, Lagier-Tourenne C (2017) Polyglutamine-expanded huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport. Neuron 94:48–57.e44. https://doi.org/10.1016/j.neuron.2017.03.027

    Article  Google Scholar 

  • Giampetruzzi A, Danielson EW, Gumina V, Jeon M, Boopathy S, Brown RH, Ratti A, Landers JE, Fallini C (2019) Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis. Nat Commun 10(1):3827. https://doi.org/10.1038/s41467-019-11837-y

    Article  Google Scholar 

  • 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 U S A 101(24):8963–8968. https://doi.org/10.1073/pnas.0402943101

    Article  Google Scholar 

  • Gonzalez-Suarez I, Redwood AB, Perkins SM, Vermolen B, Lichtensztejin D, Grotsky DA, Morgado-Palacin L, Gapud EJ, Sleckman BP, Sullivan T, Sage J, Stewart CL, Mai S, Gonzalo S (2009) Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J 28(16):2414–2427. https://doi.org/10.1038/emboj.2009.196

    Article  Google Scholar 

  • Gonzalo S, Kreienkamp R, Askjaer P (2017) Hutchinson-Gilford progeria syndrome: a premature aging disease caused by LMNA gene mutations. Ageing Res Rev 33:18–29. https://doi.org/10.1016/j.arr.2016.06.007

    Article  Google Scholar 

  • Gordon LB, Shappell H, Massaro J, D’Agostino RB Sr, Brazier J, Campbell SE, Kleinman ME, Kieran MW (2018) Association of Lonafarnib Treatment vs no treatment with mortality rate in patients with Hutchinson-Gilford progeria syndrome. JAMA 319(16):1687–1695. https://doi.org/10.1001/jama.2018.3264

    Article  Google Scholar 

  • Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, Geater C, Morozko E, Stocksdale J, Glatzer JC, Pham JT, Ahmed I, Peng Q, Wadhwa H, Pletnikova O, Troncoso JC, Duan W, Snyder SH, Ranum LPW, Thompson LM, Lloyd TE, Ross CA, Rothstein JD (2017) Mutant huntingtin disrupts the nuclear pore complex. Neuron 94:93–107.e106. https://doi.org/10.1016/j.neuron.2017.03.023

    Article  Google Scholar 

  • Guo L, Kim HJ, Wang H, Monaghan J, Freyermuth F, Sung JC, O’Donovan K, Fare CM, Diaz Z, Singh N, Zhang ZC, Coughlin M, Sweeny EA, DeSantis ME, Jackrel ME, Rodell CB, Burdick JA, King OD, Gitler AD, Lagier-Tourenne C, Pandey UB, Chook YM, Taylor JP, Shorter J (2018) Nuclear-import receptors reverse aberrant phase transitions of RNA-binding proteins with prion-like domains. Cell 173:677–692.e20. https://doi.org/10.1016/j.cell.2018.03.002

    Article  Google Scholar 

  • Haithcock E, Dayani Y, Neufeld E, Zahand AJ, Feinstein N, Mattout A, Gruenbaum Y, Liu J (2005) Age-related changes of nuclear architecture in Caenorhabditis elegans. Proc Natl Acad Sci U S A 102(46):16690–16695

    Article  Google Scholar 

  • Harhouri K, Navarro C, Baquerre C, Da Silva N, Bartoli C, Casey F, Mawuse GK, Doubaj Y, Levy N, De Sandre-Giovannoli A (2016) Antisense-based progerin downregulation in HGPS-like patients’ cells. Cells 5(3). https://doi.org/10.3390/cells5030031

  • Harhouri K, Navarro C, Depetris D, Mattei MG, Nissan X, Cau P, De Sandre-Giovannoli A, Levy N (2017) MG132-induced progerin clearance is mediated by autophagy activation and splicing regulation. EMBO Mol Med 9(9):1294–1313. https://doi.org/10.15252/emmm.201607315

    Article  Google Scholar 

  • Harhouri K, Frankel D, Bartoli C, Roll P, De Sandre-Giovannoli A, Levy N (2018) An overview of treatment strategies for Hutchinson-Gilford progeria syndrome. Nucleus 9(1):246–257. https://doi.org/10.1080/19491034.2018.1460045

    Article  Google Scholar 

  • Hayes LR, Duan L, Bowen K, Kalab P, Rothstein JD (2020) C9orf72 arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import. elife 9. https://doi.org/10.7554/eLife.51685

  • Hayflick L (1985) The cell biology of aging. Clin Geriatr Med 1(1):15–27

    Article  Google Scholar 

  • Hernandez-Segura A, Nehme J, Demaria M (2018) Hallmarks of cellular senescence. Trends Cell Biol 28(6):436–453. https://doi.org/10.1016/j.tcb.2018.02.001

    Article  Google Scholar 

  • Hilton BA, Liu J, Cartwright BM, Liu Y, Breitman M, Wang Y, Jones R, Tang H, Rusinol A, Musich PR, Zou Y (2017) Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes. FASEB J 31(9):3882–3893. https://doi.org/10.1096/fj.201700014R

    Article  Google Scholar 

  • Ho CY, Lammerding J (2012) Lamins at a glance. J Cell Sci 125(Pt 9):2087–2093. https://doi.org/10.1242/jcs.087288

    Article  Google Scholar 

  • Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, Bohr VA (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15(10):565–581. https://doi.org/10.1038/s41582-019-0244-7

    Article  Google Scholar 

  • Hunot S, Brugg B, Ricard D, Michel PP, Muriel MP, Ruberg M, Faucheux BA, Agid Y, Hirsch EC (1997) Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with Parkinson disease. Proc Natl Acad Sci U S A 94(14):7531–7536. https://doi.org/10.1073/pnas.94.14.7531

    Article  Google Scholar 

  • Ibrahim MX, Sayin VI, Akula MK, Liu M, Fong LG, Young SG, Bergo MO (2013) Targeting isoprenylcysteine methylation ameliorates disease in a mouse model of progeria. Science 340(6138):1330–1333. https://doi.org/10.1126/science.1238880

    Article  Google Scholar 

  • Ivanov A, Pawlikowski J, Manoharan I, van Tuyn J, Nelson DM, Rai TS, Shah PP, Hewitt G, Korolchuk VI, Passos JF, Wu H, Berger SL, Adams PD (2013) Lysosome-mediated processing of chromatin in senescence. J Cell Biol 202(1):129–143. https://doi.org/10.1083/jcb.201212110

    Article  Google Scholar 

  • Iyer SR, Hsia RC, Folker ES, Lovering RM (2021) Age-dependent changes in nuclear-cytoplasmic signaling in skeletal muscle. Exp Gerontol 150:111338. https://doi.org/10.1016/j.exger.2021.111338

    Article  Google Scholar 

  • Janssens GE, Meinema AC, Gonzalez J, Wolters JC, Schmidt A, Guryev V, Bischoff R, Wit EC, Veenhoff LM, Heinemann M (2015) Protein biogenesis machinery is a driver of replicative aging in yeast. elife 4:e08527. https://doi.org/10.7554/eLife.08527

    Article  Google Scholar 

  • Johnson BS, Snead D, Lee JJ, McCaffery JM, Shorter J, Gitler AD (2009) TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 284(30):20329–20339. https://doi.org/10.1074/jbc.M109.010264

    Article  Google Scholar 

  • Jovicic A, Mertens J, Boeynaems S, Bogaert E, Chai N, Yamada SB, Paul JW 3rd, Sun S, Herdy JR, Bieri G, Kramer NJ, Gage FH, Van Den Bosch L, Robberecht W, Gitler AD (2015) Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS. Nat Neurosci 18(9):1226–1229. https://doi.org/10.1038/nn.4085

    Article  Google Scholar 

  • Kang HT, Park JT, Choi K, Choi HJC, Jung CW, Kim GR, Lee YS, Park SC (2017) Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome. Aging Cell 16(3):541–550. https://doi.org/10.1111/acel.12584

    Article  Google Scholar 

  • Khilan AA, Al-Maslamani NA, Horn HF (2021) Cell stretchers and the LINC complex in mechanotransduction. Arch Biochem Biophys 702:108829. https://doi.org/10.1016/j.abb.2021.108829

    Article  Google Scholar 

  • Kutay U, Juhlen R, Antonin W (2021) Mitotic disassembly and reassembly of nuclear pore complexes. Trends Cell Biol 31(12):1019–1033. https://doi.org/10.1016/j.tcb.2021.06.011

    Article  Google Scholar 

  • Larrieu D, Vire E, Robson S, Breusegem SY, Kouzarides T, Jackson SP (2018) Inhibition of the acetyltransferase NAT10 normalizes progeric and aging cells by rebalancing the Transportin-1 nuclear import pathway. Sci Signal 11(537). https://doi.org/10.1126/scisignal.aar5401

  • Lee HG, Ueda M, Miyamoto Y, Yoneda Y, Perry G, Smith MA, Zhu X (2006) Aberrant localization of importin alpha1 in hippocampal neurons in Alzheimer disease. Brain Res 1124(1):1–4. https://doi.org/10.1016/j.brainres.2006.09.084

    Article  Google Scholar 

  • Lin YC, Kumar MS, Ramesh N, Anderson EN, Nguyen AT, Kim B, Cheung S, McDonough JA, Skarnes WC, Lopez-Gonzalez R, Landers JE, Fawzi NL, Mackenzie IRA, Lee EB, Nickerson JA, Grunwald D, Pandey UB, Bosco DA (2021) Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway. Nat Neurosci 24(8):1077–1088. https://doi.org/10.1038/s41593-021-00859-9

    Article  Google Scholar 

  • Liu J, Hetzer MW (2021) Nuclear pore complex maintenance and implications for age-related diseases. Trends Cell Biol 32:216–227. https://doi.org/10.1016/j.tcb.2021.10.001

    Article  Google Scholar 

  • Liu J, Rolef Ben-Shahar T, Riemer D, Treinin M, Spann P, Weber K, Fire A, Gruenbaum Y (2000) Essential roles for Caenorhabditis elegans lamin gene in nuclear organization, cell cycle progression, and spatial organization of nuclear pore complexes. Mol Biol Cell 11(11):3937–3947

    Article  Google Scholar 

  • Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadinanos J, Lopez-Otin C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11(7):780–785. https://doi.org/10.1038/nm1266

    Article  Google Scholar 

  • Lochs SJA, Kefalopoulou S, Kind J (2019) Lamina associated domains and gene regulation in development and cancer. Cell 8(3). https://doi.org/10.3390/cells8030271

  • Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217. https://doi.org/10.1016/j.cell.2013.05.039

    Article  Google Scholar 

  • Lord CL, Timney BL, Rout MP, Wente SR (2015) Altering nuclear pore complex function impacts longevity and mitochondrial function in S. cerevisiae. J Cell Biol 208:729–744. https://doi.org/10.1083/jcb.201412024

    Article  Google Scholar 

  • Luo YB, Mitrpant C, Johnsen RD, Fabian VA, Fletcher S, Mastaglia FL, Wilton SD (2013) Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles. Int J Clin Exp Pathol 6(12):2778–2786

    Google Scholar 

  • Manley HR, Keightley MC, Lieschke GJ (2018) The neutrophil nucleus: an important influence on neutrophil migration and function. Front Immunol 9:2867. https://doi.org/10.3389/fimmu.2018.02867

    Article  Google Scholar 

  • Mann JR, Gleixner AM, Mauna JC, Gomes E, DeChellis-Marks MR, Needham PG, Copley KE, Hurtle B, Portz B, Pyles NJ, Guo L, Calder CB, Wills ZP, Pandey UB, Kofler JK, Brodsky JL, Thathiah A, Shorter J, Donnelly CJ (2019) RNA binding antagonizes neurotoxic phase transitions of TDP-43. Neuron 102:321–338.e8. https://doi.org/10.1016/j.neuron.2019.01.048

    Article  Google Scholar 

  • Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB, Brewer CC, Zalewski C, Kim HJ, Solomon B, Brooks BP, Gerber LH, Turner ML, Domingo DL, Hart TC, Graf J, Reynolds JC, Gropman A, Yanovski JA, Gerhard-Herman M, Collins FS, Nabel EG, Cannon RO 3rd, Gahl WA, Introne WJ (2008) Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 358(6):592–604. https://doi.org/10.1056/NEJMoa0706898

    Article  Google Scholar 

  • Mertens J, Paquola AC, Ku M, Hatch E, Bohnke L, Ladjevardi S, McGrath S, Campbell B, Lee H, Herdy JR, Goncalves JT, Toda T, Kim Y, Winkler J, Yao J, Hetzer MW, Gage FH (2015) Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell 17(6):705–718. https://doi.org/10.1016/j.stem.2015.09.001

    Article  Google Scholar 

  • Moore S, Rabichow BE, Sattler R (2020) The Hitchhiker’s guide to nucleocytoplasmic trafficking in neurodegeneration. Neurochem Res 45(6):1306–1327. https://doi.org/10.1007/s11064-020-02989-1

    Article  Google Scholar 

  • Moulson CL, Fong LG, Gardner JM, Farber EA, Go G, Passariello A, Grange DK, Young SG, Miner JH (2007) Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes. Hum Mutat 28(9):882–889. https://doi.org/10.1002/humu.20536

    Article  Google Scholar 

  • Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133. https://doi.org/10.1126/science.1134108

    Article  Google Scholar 

  • Novelli G, Muchir A, Sangiuolo F, Helbling-Leclerc A, D’Apice MR, Massart C, Capon F, Sbraccia P, Federici M, Lauro R, Tudisco C, Pallotta R, Scarano G, Dallapiccola B, Merlini L, Bonne G (2002) Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet 71(2):426–431. https://doi.org/10.1086/341908

    Article  Google Scholar 

  • Ori A, Toyama BH, Harris MS, Bock T, Iskar M, Bork P, Ingolia NT, Hetzer MW, Beck M (2015) Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats. Cell Syst 1(3):224–237. https://doi.org/10.1016/j.cels.2015.08.012

    Article  Google Scholar 

  • 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. https://doi.org/10.1126/scitranslmed.3002847

    Article  Google Scholar 

  • Pentzold C, Kokal M, Pentzold S, Weise A (2021) Sites of chromosomal instability in the context of nuclear architecture and function. Cell Mol Life Sci 78(5):2095–2103. https://doi.org/10.1007/s00018-020-03698-2

    Article  Google Scholar 

  • Perez-Jimenez MM, Rodriguez-Palero MJ, Rodenas E, Askjaer P, Munoz MJ (2014) Age-dependent changes of nuclear morphology are uncoupled from longevity in Caenorhabditis elegans IGF/insulin receptor daf-2 mutants. Biogerontology 15(3):279–288. https://doi.org/10.1007/s10522-014-9497-0

    Article  Google Scholar 

  • Puente XS, Quesada V, Osorio FG, Cabanillas R, Cadinanos J, Fraile JM, Ordonez GR, Puente DA, Gutierrez-Fernandez A, Fanjul-Fernandez M, Levy N, Freije JM, Lopez-Otin C (2011) Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am J Hum Genet 88(5):650–656. https://doi.org/10.1016/j.ajhg.2011.04.010

    Article  Google Scholar 

  • Ragnauth CD, Warren DT, Liu Y, McNair R, Tajsic T, Figg N, Shroff R, Skepper J, Shanahan CM (2010) Prelamin a acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 121(20):2200–2210. https://doi.org/10.1161/CIRCULATIONAHA.109.902056

    Article  Google Scholar 

  • Rempel IL, Crane MM, Thaller DJ, Mishra A, Jansen DP, Janssens G, Popken P, Aksit A, Kaeberlein M, van der Giessen E, Steen A, Onck PR, Lusk CP, Veenhoff LM (2019) Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics. elife 8. https://doi.org/10.7554/eLife.48186

  • Rempel IL, Steen A, Veenhoff LM (2020) Poor old pores-the challenge of making and maintaining nuclear pore complexes in aging. FEBS J 287:1058–1075. https://doi.org/10.1111/febs.15205

    Article  Google Scholar 

  • 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. https://doi.org/10.1093/hmg/ddr327

    Article  Google Scholar 

  • Romero-Bueno R, de la Cruz RP, Artal-Sanz M, Askjaer P, Dobrzynska A (2019) Nuclear organization in stress and aging. Cell 8(7). https://doi.org/10.3390/cells8070664

  • Rzepecki R, Gruenbaum Y (2018) Invertebrate models of Lamin diseases. Nucleus 9(1):227–234. https://doi.org/10.1080/19491034.2018.1454166

    Article  Google Scholar 

  • Santiago-Fernandez O, Osorio FG, Quesada V, Rodriguez F, Basso S, Maeso D, Rolas L, Barkaway A, Nourshargh S, Folgueras AR, Freije JMP, Lopez-Otin C (2019) Development of a CRISPR/Cas9-based therapy for Hutchinson-Gilford progeria syndrome. Nat Med 25(3):423–426. https://doi.org/10.1038/s41591-018-0338-6

    Article  Google Scholar 

  • Savas JN, Toyama BH, Xu T, Yates JR 3rd, Hetzer MW (2012) Extremely long-lived nuclear pore proteins in the rat brain. Science 335(6071):942. https://doi.org/10.1126/science.1217421

    Article  Google Scholar 

  • Scaffidi P, Misteli T (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11(4):440–445. https://doi.org/10.1038/nm1204

    Article  Google Scholar 

  • Scaffidi P, Misteli T (2006) Lamin A-dependent nuclear defects in human aging. Science 312(5776):1059–1063. https://doi.org/10.1126/science.1127168

    Article  Google Scholar 

  • Schmidt HB, Gorlich D (2016) Transport selectivity of nuclear pores, phase separation, and Membraneless organelles. Trends Biochem Sci 41(1):46–61. https://doi.org/10.1016/j.tibs.2015.11.001

    Article  Google Scholar 

  • Schuller AP, Wojtynek M, Mankus D, Tatli M, Kronenberg-Tenga R, Regmi SG, Dip PV, Lytton-Jean AKR, Brignole EJ, Dasso M, Weis K, Medalia O, Schwartz TU (2021) The cellular environment shapes the nuclear pore complex architecture. Nature 598(7882):667–671. https://doi.org/10.1038/s41586-021-03985-3

    Article  Google Scholar 

  • Sears RM, Roux KJ (2020) Diverse cellular functions of barrier-to-autointegration factor and its roles in disease. J Cell Sci 133(16). https://doi.org/10.1242/jcs.246546

  • Shah PP, Donahue G, Otte GL, Capell BC, Nelson DM, Cao K, Aggarwala V, Cruickshanks HA, Rai TS, McBryan T, Gregory BD, Adams PD, Berger SL (2013) Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev 27(16):1787–1799. https://doi.org/10.1101/gad.223834.113

    Article  Google Scholar 

  • Springhower CE, Rosen MK, Chook YM (2020) Karyopherins and condensates. Curr Opin Cell Biol 64:112–123. https://doi.org/10.1016/j.ceb.2020.04.003

    Article  Google Scholar 

  • Steglich B, Filion GJ, van Steensel B, Ekwall K (2012) The inner nuclear membrane proteins Man1 and Ima1 link to two different types of chromatin at the nuclear periphery in S. pombe. Nucleus 3:77–87

    Article  Google Scholar 

  • Suhr ST, Senut MC, Whitelegge JP, Faull KF, Cuizon DB, Gage FH (2001) Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. J Cell Biol 153(2):283–294. https://doi.org/10.1083/jcb.153.2.283

    Article  Google Scholar 

  • Taylor JP, Brown RH Jr, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539(7628):197–206. https://doi.org/10.1038/nature20413

    Article  Google Scholar 

  • Toyama BH, Savas JN, Park SK, Harris MS, Ingolia NT, Yates JR 3rd, Hetzer MW (2013) Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell 154(5):971–982. https://doi.org/10.1016/j.cell.2013.07.037

    Article  Google Scholar 

  • Ungricht R, Kutay U (2017) Mechanisms and functions of nuclear envelope remodelling. Nat Rev Mol Cell Biol 18:229–245. https://doi.org/10.1038/nrm.2016.153

    Article  Google Scholar 

  • van Steensel B, Furlong EEM (2019) The role of transcription in shaping the spatial organization of the genome. Nat Rev Mol Cell Biol 20:327–337. https://doi.org/10.1038/s41580-019-0114-6

    Article  Google Scholar 

  • 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 JM, 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. https://doi.org/10.1038/nm1786

    Article  Google Scholar 

  • Winton MJ, Igaz LM, Wong MM, Kwong LK, Trojanowski JQ, Lee VM (2008) Disturbance of nuclear and cytoplasmic TAR DNA-binding protein (TDP-43) induces disease-like redistribution, sequestration, and aggregate formation. J Biol Chem 283(19):13302–13309. https://doi.org/10.1074/jbc.M800342200

    Article  Google Scholar 

  • Woerner AC, Frottin F, Hornburg D, Feng LR, Meissner F, Patra M, Tatzelt J, Mann M, Winklhofer KF, Hartl FU, Hipp MS (2016) Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science 351(6269):173–176. https://doi.org/10.1126/science.aad2033

    Article  Google Scholar 

  • Worman HJ, Schirmer EC (2015) Nuclear membrane diversity: underlying tissue-specific pathologies in disease? Curr Opin Cell Biol 34:101–112. https://doi.org/10.1016/j.ceb.2015.06.003

    Article  Google Scholar 

  • Xiong ZM, Choi JY, Wang K, Zhang H, Tariq Z, Wu D, Ko E, LaDana C, Sesaki H, Cao K (2016) Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria. Aging Cell 15(2):279–290. https://doi.org/10.1111/acel.12434

    Article  Google Scholar 

  • Zetka M, Paouneskou D, Jantsch V (2020) The nuclear envelope, a meiotic jack-of-all-trades. Curr Opin Cell Biol 64:34–42. https://doi.org/10.1016/j.ceb.2019.12.010

    Article  Google Scholar 

  • Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE, Rothstein JD (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525(7567):56–61. https://doi.org/10.1038/nature14973

    Article  Google Scholar 

  • Zhang K, Daigle JG, Cunningham KM, Coyne AN, Ruan K, Grima JC, Bowen KE, Wadhwa H, Yang P, Rigo F, Taylor JP, Gitler AD, Rothstein JD, Lloyd TE (2018) Stress granule assembly disrupts nucleocytoplasmic transport. Cell 173:958–971.e17. https://doi.org/10.1016/j.cell.2018.03.025

    Article  Google Scholar 

  • Zhang J, Velmeshev D, Hashimoto K, Huang YH, Hofmann JW, Shi X, Chen J, Leidal AM, Dishart JG, Cahill MK, Kelley KW, Liddelow SA, Seeley WW, Miller BL, Walther TC, Farese RV Jr, Taylor JP, Ullian EM, Huang B, Debnath J, Wittmann T, Kriegstein AR, Huang EJ (2020) Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency. Nature 588(7838):459–465. https://doi.org/10.1038/s41586-020-2709-7

    Article  Google Scholar 

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Acknowledgments

We are grateful to Marta Artal Sanz and Antonio Miranda Vizuete for critical reading of the manuscript and to Victor Carranco Fabre for help with figures. We also wish to acknowledge funding from the Spanish State Research Agency (doi: 10.13039/501100011033; PID2019-105069GB-I00 and CEX2020-001088-M), the Regional Government of Andalusia (P20_00873) and the European Regional Development Fund “Una manera de hacer Europa”.

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  1. Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Pablo de Olavide, Sevilla, Spain

    Adrián Fragoso-Luna & Peter Askjaer

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  1. Adrián Fragoso-Luna
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Correspondence to Peter Askjaer .

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  1. Institute for Molecular Physiology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK

    Viktor I. Korolchuk

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Fragoso-Luna, A., Askjaer, P. (2023). The Nuclear Envelope in Ageing and Progeria. In: Harris, J.R., Korolchuk, V.I. (eds) Biochemistry and Cell Biology of Ageing: Part III Biomedical Science. Subcellular Biochemistry, vol 102. Springer, Cham. https://doi.org/10.1007/978-3-031-21410-3_3

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