Skip to main content

Advertisement

SpringerLink
Log in

Hutchinson–Gilford Progeria Syndrome: A Premature Aging Disease

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Progeria is sporadic, very rare, autosomal dominant, deadly childhood disorder. It is one of the progeroid syndromes also known as Hutchinson–Gilford progeria syndrome (HGPS). Aging is a developmental process that begins with fertilization and ends up with death involving a lot of environmental and genetic factors. The disease firstly involves premature aging and then death from complications of atherosclerosis such as myocardial infarction, stroke, atherosclerosis, or heart failure. The lifespan of the patient is normally up to teen age or early twenties. It is usually not inherited because a patient normally dies before the age of reproduction. The most important genetic linkage between progeria and aging is shortening of telomere ends with each replication cycle. The patients are normally observed to have extremely short telomeres. Currently, 90% of the patients are said to have de novo point mutations in the LMNA gene that substitute cytosine with thymine and have been found in individuals with HGPS. Lmna encodes lamins A and C, and the A-type lamins have important structural function in the nuclear envelope. The most common type of HGPS mutation is located at codon 608 (G608G). It could not be diagnosed at birth, but after the age of 2 years, visible, prominent symptoms can be observed. Still, lot of research is needed to solve this mystery; hopefully, future research on HGPS would provide important clues for progeria and other fatal age-related disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Hutchinson J (1886) Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages in a boy whose mother had been almost totally bald from alopecia areata from the age six. Medicochir Trans 69:473–477

    CAS  Google Scholar 

  2. Gilford H (1897) On a condition of mixed premature and immature development. Med Chirurg Trans 80:17–45

    Article  CAS  Google Scholar 

  3. Gilford H (1904) Progeria: a form of senilism. Practitioner 73:188–217

    Google Scholar 

  4. Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith ACM, Perry MB, Brewer CC, Zalewski C et al (2010) Phenotype and course of Hutchinson–Gilford progeria syndrome. N Engl J Med 358(6):592–604. doi:10.1056/NEJMoa0706898Published in final edited form as: N Engl J Med. 2008 February 7

  5. Hennekam RC (2006) Hutchinson–Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 140A:2603–2624. doi:10.1002/ajmg.a.31346

    Article  CAS  Google Scholar 

  6. Sternberg S (2003) Gene found for rapid aging disease in children. USA Today. http://www.usatoday.com/news/science/2003-04-16-agin-gene_x.htm. Retrieved 2006–12-13

  7. Steve Roach E, Miller VS (2004) Cambridge University Press, vol 36, p 150

  8. Rakha P, Gupta A, Dhingra G, Nagpal M (2011) Hutchinson–Gilford progeria syndrome: a review. Der Pharmacia Sinica 2(1):110–117

    CAS  Google Scholar 

  9. Hsiao K-J (1998) Adv Clin Chem 33:10

    Google Scholar 

  10. Quick facts as of April 1, 2017. Progeria Research Foundation. https://www.progeriaresearch.org/quick-facts/. Accessed 14 June 2017

  11. De Busk FL (1972) The Hutchinson-Gilford progeria syndrome. J Pediatr 90:697–724

    Article  Google Scholar 

  12. Beauregard S, Gilchrest BA (1987) Syndromes of premature aging. Dermatol Clin 5:109–121

    CAS  PubMed  Google Scholar 

  13. Brown WT, Kieras FJ, Houck GE Jr, Dutkowski R, Jenkins EC (1985) A comparison of adult and childhood progerias: Werner syndrome and Hutchinson-Gilford progeria syndrome. Adv Exp Med Biol 190:229–244

    Article  CAS  PubMed  Google Scholar 

  14. Brown WT (1987) Premature aging syndromes. Curr Probl Dermatol 17:152–165

    Article  CAS  PubMed  Google Scholar 

  15. Korf B (2008) N Engl J Med 358(6):552–555

    Article  CAS  PubMed  Google Scholar 

  16. Rakha P et al (2011) Der Pharmacia Sinica 2(1):110–117

    CAS  Google Scholar 

  17. Balin AD (ed) (1989) Contribution of in vitro skin fibroblast studies from individuals with genetic disease that predispose to accelerated aging phenomena to our understanding of the aging process. Raven Press, New York, pp. 93–9l 19

    Google Scholar 

  18. Progeria Research Foundation (2016) https://www.progeriaresearch.org/meet-the-kids/. Accessed 14 June 2017

  19. Pesce K, Rothe MJ (1996) The premature ageing syndromes. Clin Dermatol 14:161–170

    Article  CAS  PubMed  Google Scholar 

  20. Dyer CAE, Sinclair AJ (1998) The premature ageing syndromes: insights into the ageing process. Age Ageing 27:73–80

    Article  CAS  PubMed  Google Scholar 

  21. Bennett GCJ, Ebrahim S (1995) The essentials of health care in old age, 2nd edn. Oxford University Press, New York, pp. 3–10

    Google Scholar 

  22. Plasilova M, Chattopadhyay C, Pal P, Schaub NA, Buechner SA, Mueller H, Miny P, Ghosh A et al (2004) Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome. J Med Genet 41:609–614

  23. Smith ED, Kudlow BA, Frock RL, Kennedy BK (2005) A-type nuclear lamins, progerias and other degenerative disorders. Mech Ageing Dev 126:447–460

    Article  CAS  PubMed  Google Scholar 

  24. Kirkwood TB (2005) Understanding the odd science of aging. Cell 120:437–447

    Article  CAS  PubMed  Google Scholar 

  25. Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW (2005) DNA repair, genome stability, and aging. Cell 120:497–512

    Article  CAS  PubMed  Google Scholar 

  26. Decker ML, Chavez E, Vulto I, Lansdorp PM (2009) Telomere length in Hutchinson-Gilford progeria syndrome. Mech Ageing Dev 130(6):377–383

  27. Silvera VM, Gordon LB, Orbach DB, Campbell SE, Machan JT, Ullrich NJ (2013) Imaging characteristics of cerebrovascular arteriopathy and stroke in Hutchinson-Gilford progeria syndrome. Am J Neuroradiol 34(5):1091–1097

  28. Goss JR, Stolz DB, Robinson AR, Zhang M, Arbujas N, Robbins PD, Glorioso JC, Niedernhofer LJ (2010) Premature aging-related peripheral neuropathy in a mouse model of progeria. Mech Ageing Dev. doi:10.1016/j.mad.2011.04.010

    Google Scholar 

  29. Sarkar PK, Shinton RA (2001) Hutchinson-Gilford progeria syndrome. Postgrad Med J 77:312–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Olteanu I, Crisan M, Crisan D, Kozan A (2009) Hutchinson-Gilford syndrome. Journal Medical Aradean 02:13–18

    Google Scholar 

  31. Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I (1998) X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 19(1):6–7

    Article  Google Scholar 

  32. DeBusk FL (1972) The Hutchinson-Gilford progeria syndrome: report of 4 cases and review of the literature. J Pediatrics 80(4):697–724

    Article  CAS  Google Scholar 

  33. Uitto J (2001) Searching for clues to premature aging. The workshop on Hutchinson–Gilford Progeria Syndrome was held at Bethesda, MD, USA, 28 and 29 November

  34. Kumar S, Kumar A, Singla M, Singh A (2010) Hutchinson-Gilford syndrome (progeria). Int J Pharm Bio Sci 1(3)

  35. Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB et al (2008) Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 358:592–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dominguez-Gerpe L, Araijo-Vilar D (2008) Prematurely aged children; molecular alteration leading to Hutchinson-Gilford progeria and Werner syndromes. Current aging Sci 1:202–212

    Article  CAS  Google Scholar 

  37. Hennekam RC (2006) Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 140:2603–2624

    Article  PubMed  Google Scholar 

  38. Ackerman J, Gilbet-Barness E (2002) Hutchinson-Gilford progeria syndrome: a pathologic study. Pediatr Pathol Mol Med 21:1–13

    Article  PubMed  Google Scholar 

  39. Ishii T (1976) Progeria: autopsy report of one case, with a review of pathologic findings reported in a literature. J Am Geriatr Soc 24:193–202

    Article  CAS  PubMed  Google Scholar 

  40. Corcoy R, Aris A, de Leiva A (1989) Fertility in a case of progeria. Am J Med Sci 297:383–384

    Article  CAS  PubMed  Google Scholar 

  41. Sadeghi-Nejad A, Demmer L (2007) Growth hormone therapy in progeria. J Pediatr Endocrinol Metab 20(5):633–637

    Article  CAS  PubMed  Google Scholar 

  42. Hennekam RC (2006) Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet 140:2603–2624

    Article  PubMed  Google Scholar 

  43. Arlan L (1971) Am Heart J 82:287–289

    Article  Google Scholar 

  44. Gorlin RO, Sedano HO (1968) Progeria Hutchinson-Gilford syndrome. Mod Med 46:62

    Google Scholar 

  45. Batstone MD, Macleod AW (2002) Oral and maxillofacial surgical considerations for a case of Hutchinson-Gilford progeria. Int J Paediatr Dent 12:429–432

    Article  CAS  PubMed  Google Scholar 

  46. Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB et al (2008) Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 358:592–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shiraishi I, Hayashi S, Hirai E, Onouchi Z, Hamaoka K (2001) Fatal pulmonary hypertension associated with an atypical case of Hunchinson-Gilford progeria. Pediatr Cardiol 22:530–533

    Article  CAS  PubMed  Google Scholar 

  48. Stehbens WE, Wakefield SJ, Gilbert-Barness E, Olson RE, Ackerman J (1999) Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc Pathol 8:29–39

    Article  CAS  PubMed  Google Scholar 

  49. Atkins L (1954) Progeria: report of a case with post-mortem findings. N Engl J Med 250:1065–1069

    Article  CAS  PubMed  Google Scholar 

  50. Ishii T (1976) Progeria: autopsy report of one case, with a review of pathologic findings reported in the literature. J Am Geriatr Soc 24:193–202

    Article  CAS  PubMed  Google Scholar 

  51. Corcoy R, Aris A, de Leiva A (1989) Fertility in a case of progeria. Am J Med Sci 297:383–384

    Article  CAS  PubMed  Google Scholar 

  52. DeBusk FL (1972) The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr 80:697–724

    Article  CAS  PubMed  Google Scholar 

  53. Gabr M, Hashem N, Hashem M, Fahmi A, Safouh M (1960) Progeria, a pathologic study. J Pediatr 57:70–77

    Article  CAS  PubMed  Google Scholar 

  54. Dyck JD, David TE, Burke B, Webb GD, Henderson MA, Fowler RS (1987) Management of coronary artery disease in Hutchinson-Gilford syndrome. J Pediatr 111:407–410

    Article  CAS  PubMed  Google Scholar 

  55. Khalifa MM (1989) Hutchinson–Gilford progeria syndrome: report of a Libyan family and evidence of autosomal recessive inheritance. Clin Genet 35:125–132

    Article  CAS  PubMed  Google Scholar 

  56. Maciel AT (1988) Evidence for autosomal recessive inheritance of progeria (Hutchinson Gilford). Am J Med Genet 31:483–487

    Article  CAS  PubMed  Google Scholar 

  57. Brown WT (1979) Human mutations affecting aging—a review. Mech Ageing Dev 9:325–336

    Article  CAS  PubMed  Google Scholar 

  58. Delgado Luengo W, Rojas Martinez A, Ortiz Lopez R et al (2002) Del(1)(q23) in a patient with Hutchinson–Gilford progeria. Am J Med Genet 113:298–301

    Article  PubMed  Google Scholar 

  59. Brown WT, Adbenur J, Goonewardena P et al (1990) Hutchinson–Gilford progeria syndrome: clinical and metabolic abnormalities (abstract). Am J Hum Genet 47:A50

    Google Scholar 

  60. De Sandre-Giovannoli A, Bernard R, Cau P et al (2003) Lamin A truncation in Hutchinson–Gilford progeria. Science 300:2055

    Article  CAS  PubMed  Google Scholar 

  61. Cao H, Hegele RA (2003) Lmna is mutated in Hutchinson–Gilford progeria (MIM 176670) but not in Wiedemann–Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet 48:271–274

    Article  CAS  PubMed  Google Scholar 

  62. Shanker P, Vishisanth P, Vijay Nath D, Naveen C, Kiran Kumar Y, Venkateshwarlu P (2010) Progeria. A brief review. Intr J Pharma & Bio Sciences 1(2)

  63. Plasilova M, Chattopadhyay C, Pal P, Schaub NA, Buechner SA, Mueller H et al (2004) Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome. J Med Genet 41:609–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 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 41:304–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fukuchi K, Katsuya T, Sugimoto K, Kuremura M, Kim HD, Li L et al (2004) LMNA mutation in a 45 year old Japanese subject with Hutchinson-Gilford progeria syndrome. J Med Genet 41:e67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Verstraeten VL, Broers JL, van Steensel MA, Zinn-Justin S, Ramaekers FC, Steijlen PM et al (2006) Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation. Hum Mol Genet 15:2509–2522

    Article  CAS  PubMed  Google Scholar 

  67. Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y et al (2003) LMNA mutations in atypical Werner’s syndrome. Lancet 362:440–445

    Article  CAS  PubMed  Google Scholar 

  68. Cox LS, Faragher RG (2007) From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing. Cell Mol Life Sci 64:2620–2641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Scaffidi P, Misteli T (2006) Lamin A-dependent nuclear defects in human aging. Science 312(5776):1059–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wilson KL, Berk JM (2010) The nuclear envelope at a glance. J Cell Sci 123:1973–1978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Vergnes L, Peterfy M, Bergo MO, Young SG, Reue K (2004) Lamin B1 is required for mouse development and nuclear integrity. Proc Natl AcadSci USA 101:10428–10433

    Article  CAS  Google Scholar 

  72. Lammerding J, Fong LG, Ji JY, Reue K, Stewart CL et al (2006) Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem 281:25768–25780

    Article  CAS  PubMed  Google Scholar 

  73. Lin F, Worman HJ (1993) Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C. J Biol Chem 268:16321–16326

    CAS  PubMed  Google Scholar 

  74. Weber K, Plessmann U, Traub P (1989) Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina. FEBS Lett 257:411–414

    Article  CAS  PubMed  Google Scholar 

  75. Fong LG, Ng JK, Lammerding J, Vickers TA, Meta M, Cote N et al (2006) Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest 116:743–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Worman HJ, Ostlund C, Wang Y (2010) Diseases of the nuclear envelope. Cold Spring Harb Perspect Biol 2:a000760

    Article  PubMed  PubMed Central  Google Scholar 

  77. Worman HJ, Bonne G (2007) “Laminopathies”: a wide spectrum of human diseases. Exp Cell Res 313:2121–2133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. The Human Gene Mutation Database (at the Institute of Medical Genetics in Cardiff). http://www.hgmd.cf.ac.uk/ac/all.php. Accessed 14 June 2017

  79. Qin Z, Kalinowski A, Dahl KN, Buehler MJ (2011) Structure and stability of the lamin A tail domain and HGPS mutant. J Struct Biol. doi:10.1016/j.jsb.2011.05.015

    PubMed Central  Google Scholar 

  80. Sullivan T et al (1999) Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147:913–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Nikolova V et al (2004) Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. J Clin Invest 113:357–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. De Sandre-Giovannoli A et al (2002) Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot–Marie–Tooth disorder type 2) and mouse. Am J Hum Genet 70:726–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Broers JL, Ramaekers FC, Bonne G, Yaou RB, Hutchison CJ (2006) Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev 86:967–1008

    Article  CAS  PubMed  Google Scholar 

  84. Fong LG, Ng JK, Meta M, Cote N, Yang SH, Stewart CL et al (2004) Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc Natl Acad Sci U S A 101:18111–18116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Scaffidi P, Misteli T (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11:440–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL et al (2005) Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc Natl Acad Sci U S A 102:12873–12878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Gruber J, Lampe T, Osborn M, Weber K (2005) RNAi of FACE1 protease results in growth inhibition of human cells expressing lamin A: implications for Hutchinson-Gilford progeria syndrome. J Cell Sci 118:689–696

    Article  CAS  PubMed  Google Scholar 

  88. Subba RK (2007) Mechanisms of disease: DNA repair defects and neurological disease. Nat Clin Pract Neurol 3:162–172

    Article  Google Scholar 

  89. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X et al (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11:780–785

    Article  CAS  PubMed  Google Scholar 

  90. Manju K, Muralikrishna B, Parnaik VK (2006) Expression of disease causing lamin A mutants impairs the formation of DNA repair foci. J Cell Sci 119:2704–2714. doi:10.1242/jcs.03009

    Article  CAS  PubMed  Google Scholar 

  91. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR et al (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A 103:8703–8708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Varela I, Cadinanos J, Pendas AM, Gutierrez-Fernandez A, Folgueras AR, Sanchez LM et al (2005) Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437:564–568

    Article  CAS  PubMed  Google Scholar 

  93. Atadja P, Wong H, Garkavtsev I, Veillette C, Riabowol K (1995) Increased activity of p53 in senescing fibroblasts. Proc Natl AcadSci USA 92:8348–8352

    Article  CAS  Google Scholar 

  94. 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 8:394–404

    Article  CAS  PubMed  Google Scholar 

  95. Therizols P, Fairhead C, Cabal GG, Genovesio A, Olivo-Marin JC, Dujon B et al (2006) Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region. J Cell Biol 172:189–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Bridger JM, Kill IR (2004) Aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis. Exp Gerontol 39:717–724

    Article  CAS  PubMed  Google Scholar 

  97. Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB et al (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl AcadSci USA 101:8963–8968

    Article  CAS  Google Scholar 

  98. Hutchison CJ, Alvarez-Reyes M, Vaughan OA (2001) Lamins in disease: why do ubiquitously expressed nuclear envelope proteins give rise to tissue-specific disease phenotypes? J Cell Sci 114:9–19

    CAS  PubMed  Google Scholar 

  99. Worman HJ, Gundersen GG (2006) Here come the SUNs: a nucleocytoskeletal missing link. Trends Cell Biol 16:67–69

    Article  CAS  PubMed  Google Scholar 

  100. Eriksson M et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423(6937):293–398

    Article  CAS  PubMed  Google Scholar 

  101. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Cao K et al (2007) A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci U S A 104(12):4949–4954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. McClintock D et al (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One 2(12):E1269

    Article  PubMed  PubMed Central  Google Scholar 

  104. Eisch V, Lu X, Gabriel D, Djabali K (2016) Progerin impairs chromosome maintenance by depleting CENP-F from metaphase kinetochores in Hutchinson-Gilford progeria fibroblasts. Oncotarget 7(17):24700

    Article  PubMed  PubMed Central  Google Scholar 

  105. Holzenberger M (2004) The GH/IGF-I axis and longevity. Eur J Endocrinol 151(Suppl 1):S23–S27

    Article  CAS  PubMed  Google Scholar 

  106. Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E et al (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444:1038–1043

    Article  CAS  PubMed  Google Scholar 

  107. Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, Smoot LB, Gordon CM et al (2012) Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci USA 109(41):16666–16671

  108. Gordon LB, Massaro J, D’Agostino RB, Campbell SE, Brazier J, Brown WT, Kleinman ME, Kieran MW (2014) Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation 130(1):27–34 CIRCULATIONAHA-113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Gordon LB, Kleinman ME, Massaro JM, D'Agostino RB, Shappell H, Gerhard-Herman M, Smoot LB, Gordon CM et al (2016) Clinical trial of protein farnesylation inhibitors lonafarnib, pravastatin and zoledronic acid in children with Hutchinson-Gilford progeria syndrome. Circulation 134(2):114–125 CIRCULATIONAHA-116

  110. Everolimus and lonafarnib. Single arm. Phase I: lonafarnib with escalating doses of everolimus to determine MTD. Phase II: lonafarnib plus everolimus at MTD (efficacy assessment). https://clinicaltrials.gov/ct2/show/NCT02579044?term=progeria+everolimus&rank=1. Accessed 14 June 2017

  111. Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, Krainc D, Collins FS (2011) Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci Transl Med 3(89):89ra58. doi:10.1126/scitranslmed.3002346

Download references

Author information

Authors and Affiliations

  1. Department of Bioinformatics and Biotechnology, Faculty of Basic and Applied Sciences, International Islamic University, Islamabad, Pakistan

    Muhammad Saad Ahmed & Asif Mir

  2. Department of Biological Engineering/Institute of Biotransformation and Synthetic Biosystem, School of Life Sciences, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China

    Muhammad Saad Ahmed

  3. Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU), 11 Fucheng Road, Beijing, 100048, People’s Republic of China

    Sana Ikram

  4. Department of Bioinformatics, Hazara University, Mansehra, Pakistan

    Nousheen Bibi

  5. National Center for Bioinformatics, Quaid-e-Azam University, Islamabad, Pakistan

    Nousheen Bibi

Authors
  1. Muhammad Saad Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sana Ikram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nousheen Bibi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Asif Mir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Asif Mir.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmed, M.S., Ikram, S., Bibi, N. et al. Hutchinson–Gilford Progeria Syndrome: A Premature Aging Disease. Mol Neurobiol 55, 4417–4427 (2018). https://doi.org/10.1007/s12035-017-0610-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-017-0610-7

Keywords

Search

Navigation