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Age-dependent changes of nuclear morphology are uncoupled from longevity in Caenorhabditis elegans IGF/insulin receptor daf-2 mutants

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Abstract

Nuclear envelope (NE) architecture and aging have been associated since the discovery that certain human progeria diseases are due to perturbations in processing of lamin A protein, generating alterations in NE morphology. However, whether changes in the NE are a causal effect of normal and premature aging is still controversial. Caenorhabditis elegans is a model organism where observations supporting both, dependent and independent roles of nuclear architecture in the aging process, have been reported. We found that the long-lived glp-1 mutant and dietary restriction delayed age-associated nuclear morphology changes. In addition, we observed that the long-lived mutant of the insulin/IGF receptor daf-2 delayed the age-dependent changes of nuclear architecture at 25 °C, as previously described. However, when daf-2 animals were incubated at 20 °C they remained long-lived, but nuclear appearance changed at similar rate as in the wild type. This supports the idea that both phenotypes, longevity and maintenance of nuclear architecture are tightly associated but can be separated and argues that nuclear morphology deterioration is not a cause of the natural aging process.

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References

  • Ahearn IM, Haigis K, Bar-Sagi D, Philips MR (2012) Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol 13(1):39–51. doi:10.1038/nrm3255

    Article  CAS  Google Scholar 

  • Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295(5554):502–505. doi:10.1126/science.1065768

    Article  CAS  PubMed  Google Scholar 

  • Bar DZ, Gruenbaum Y (2010) Reversal of age-dependent nuclear morphology by inhibition of prenylation does not affect lifespan in Caenorhabditis elegans. Nucleus 1(6):499–505. doi:10.4161/nucl.1.6.13223

    PubMed Central  PubMed  Google Scholar 

  • Bar DZ, Neufeld E, Feinstein N, Gruenbaum Y (2009) Gliotoxin reverses age-dependent nuclear morphology phenotypes, ameliorates motility, but fails to affect lifespan of adult Caenorhabditis elegans. Cell Motil Cytoskelet 66(10):791–797. doi:10.1002/cm.20347

    Article  CAS  Google Scholar 

  • Chen D, Thomas EL, Kapahi P (2009) HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet 5(5):e1000486. doi:10.1371/journal.pgen.1000486

    Article  PubMed Central  PubMed  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. doi:10.1038/nature01629

    Article  CAS  PubMed  Google Scholar 

  • Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV, Edgley ML, Larsen PL, Riddle DL (1998) Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150(1):129–155

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed Central  PubMed  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 USA 102(46):16690–16695

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512. doi:10.1038/nature08980

    Article  CAS  PubMed  Google Scholar 

  • Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278(5341):1319–1322

    Article  CAS  PubMed  Google Scholar 

  • Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389(6654):994–999. doi:10.1038/40194

    Article  CAS  PubMed  Google Scholar 

  • Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G (1999) A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13(11):1438–1452

    Article  CAS  PubMed Central  PubMed  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. doi:10.1016/j.ajhg.2011.04.010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Raz V, Vermolen BJ, Garini Y, Onderwater JJ, Mommaas-Kienhuis MA, Koster AJ, Young IT, Tanke H, Dirks RW (2008) The nuclear lamina promotes telomere aggregation and centromere peripheral localization during senescence of human mesenchymal stem cells. J Cell Sci 121(Pt 24):4018–4028. doi:10.1242/jcs.034876

    Article  CAS  PubMed  Google Scholar 

  • Reddy S, Comai L (2012) Lamin A, farnesylation and aging. Exp Cell Res 318(1):1–7. doi:10.1016/j.yexcr.2011.08.009

    Article  CAS  PubMed  Google Scholar 

  • Righolt CH, van ‘t Hoff ML, Vermolen BJ, Young IT, Raz V (2011) Robust nuclear lamina-based cell classification of aging and senescent cells. Aging (Albany NY) 3(12):1192–1201

    CAS  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stiernagle T (2006) Maintenance of C. elegans. WormBook:1–11. doi:10.1895/wormbook.1.101.1

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Wolkow CA, Munoz MJ, Riddle DL, Ruvkun G (2002) Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway. J Biol Chem 277(51):49591–49597. doi:10.1074/jbc.M207866200

    Article  CAS  PubMed  Google Scholar 

  • Worman HJ (2012) Nuclear lamins and laminopathies. J Pathol 226(2):316–325. doi:10.1002/path.2999

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

We wish to thank Y. Gruenbaum for the PD4810 strain and J. Rueda-Carrasco for technical assistance as well as M. Artal-Sanz, A.M. Brokate-Llanos and A. Miranda-Vizuete for discussion on the manuscript. This work was funded by the Autonomous Government of Andalusia (P07-CVI-02697). In addition, we wish to acknowledge Fundación Ramón Areces for a fellowship to ER. Some nematode strains used in this work were provided by the “Caenorhabditis Genetic Center”, which is funded by the NIH National Center for Research Resources (NCRR).

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Correspondence to Peter Askjaer or Manuel J. Muñoz.

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Pérez-Jiménez, M.M., Rodríguez-Palero, M.J., Ródenas, E. et al. Age-dependent changes of nuclear morphology are uncoupled from longevity in Caenorhabditis elegans IGF/insulin receptor daf-2 mutants. Biogerontology 15, 279–288 (2014). https://doi.org/10.1007/s10522-014-9497-0

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