Skip to main content
SpringerLink
Log in

Embryonic Stem Cells: Prospects of Regenerative Medicine for the Treatment of Human Aging

  • Chapter
  • First Online:
The Future of Aging

Abstract

The human somatic/germ-line dichotomy is characterized by somatic cell lineages displaying a finite replicative capacity and germ-line cells that possess the potential for replicative immortality. The in vitro culture of somatic cells has demonstrated that in the absence of genotoxic stress, replicative senescence is due to the repression of telomerase activity and a resulting progressive shortening of telomeres. A growing body of data supports the role of telomeric DNA damage not merely in senescence in vitro, but in age-related disease and in premature aging syndromes such as Werner syndrome. The unique properties of cultured human embryonic stem (hES) cells, such as their replicative immortality through a high level of telomerase expression, makes these cells an attractive source for the manufacture of young human cell types of all types. The emerging technologies allowing the reprogramming of a patient’s somatic cells back to a germ-line state and the resetting of telomere length has enabled the emerging field of regenerative medicine, focused on discovering primitive embryonic cell types useful in repairing tissues afflicted with degenerative disease. While in principle, all somatic cell types could be manufactured from hES cells, some cell types appear to be the easiest to scale, purify, and engraft in adult tissues, and are therefore likely to be the first to be developed as viable products for the treatment of age-related degenerative disease.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams B, Xiao Q, Xu Q (2007) Stem cell therapy for vascular diseases. Trends Cardiovasc Med 17:246–251

    CAS  PubMed  Google Scholar 

  • Allshire RC, Gosden JR, Cross SH, Cranston G, Rout D, Sugawara N, Szostak JW, Fantes PA, Hastie ND (1988) Telomeric repeat from T thermophila cross hybridizes with human telomeres. Nature 332:656–659

    CAS  PubMed  Google Scholar 

  • Allshire RC, Dempster M, Hastie ND (1989) Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res 17:4611–4627

    CAS  PubMed  Google Scholar 

  • American Heart Association (2008) Heart disease and stroke statistics–2006 update A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113: e85–e151

    Google Scholar 

  • Amrani M, Goodwin AT, Gray CC, Yacoub MH (1996) Ageing is associated with reduced basal and stimulated release of nitric oxide by the coronary endothelium Acta Physiol Scand 157:79–84

    CAS  Google Scholar 

  • Artandi SE Alson S, Teitze MK, Sharpless NE, Ye S, Greenberg RA, Castrillon DH, Horner JW, Weiler SR, Carrasco RD, DePinho RA (2002) Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc Natl Acad Sci USA 99:8191–8196

    CAS  PubMed  Google Scholar 

  • Bai Y, Murnane JP (2003) Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Hum Genet 113:337–347

    CAS  PubMed  Google Scholar 

  • Balbarini A, Barsotti MC, Di Stefano R, Leone A, Santoni T (2007) Circulating endothelial progenitor cells characterization, function, and relationship with cardiovascular risk factors. Curr Pharm Des 13:1699–1713

    CAS  PubMed  Google Scholar 

  • Bandyopadhyay D, Gatza C, Donehower LA, Medrano EE (2005) Analysis of cellular senescence in culture in vivo: the senescence-associated beta-galactosidase assay. Curr Protoc Cell Biol Chapter 18:Unit 189

  • Barberi T, Klivenyi P, Calingasan NY, Lee H, Kawamata H, Loonam K, Perrier AL, Bruses J, Rubio ME, Topf N, Tabar V, Harrison NL, Beal MF, Moore MA, Studer L (2003) Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice. Nat Biotechnol 21:1200–1207

    CAS  PubMed  Google Scholar 

  • Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A, Kellner L, Stanzel BV, Jahn C, Feichtinger H (2004) Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci 45:4151–4160

    PubMed  Google Scholar 

  • Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu C-P, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of cell life-span by introduction of telomerase into normal human cells. Science 279:349–352

    CAS  PubMed  Google Scholar 

  • Boilson BA, Kiernan TJ, Harbuzariu A, Nelson RE, Lerman A, Simari RD (2008) Circulating CD34+ cell subsets in patients with coronary endothelial dysfunction. Nat Clin Pract Cardiovasc Med 5:489–496

    CAS  PubMed  Google Scholar 

  • Brevini TA, Antonini S, Pennarossa G, Gandolfi F (2008) Recent progress in embryonic stem cell research and its application in domestic species. Reprod Domest Anim 43(Suppl 2):193–199

    PubMed  Google Scholar 

  • Butler, RN (2008) The longevity revolution: the benefits and challenges of living a long life. Publlic Affairs, New York

    Google Scholar 

  • Canela A, Martin-Caballero J, Flores JM, Blasco MA (2004) Constitutive expression of Tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert Mice. Mol Cell Biol 24:4275–4293

    CAS  PubMed  Google Scholar 

  • Canela A, Vera E, Klatt P, Blasco MA (2007) High-thoughput telomere length quantification by FISH and its application to human population studies. Proc Natl Acad Sci USA 104:5300–5305

    CAS  PubMed  Google Scholar 

  • Carrel A (1912) On the permanent life of tissues outside of the organism. J Exp Med 15:516–527

    CAS  PubMed  Google Scholar 

  • Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361:393–395

    CAS  PubMed  Google Scholar 

  • Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA (2004) Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 36:877–882

    CAS  PubMed  Google Scholar 

  • Chiu C-P, Dragowska W, Kim NW, Vaziri H, Yui J, Thomas TE, Harley CB, Lansdorp, PM (1996) Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14:239–248

    CAS  PubMed  Google Scholar 

  • Chung JH and Eun HC (2007) Angiogenesis in skin aging and photoaging. J Dermatol 34:593–600

    CAS  PubMed  Google Scholar 

  • Cibelli JB, Kiessling AA, Cunniff K, Richards C, Lanza RP, West MD (2001) Somatic cell nuclear transfer in humans: Pronuclear and early embryonic development. e-biomed: J Regen Med 2:25–31

    Google Scholar 

  • Cibelli JB, Lanza RP, Campbell KHS, West MD (2002a) Principles of Cloning. Academic Press, New York

    Google Scholar 

  • Cibelli JB, Grant KA, Chapman KB, Cunniff K, Worst T, Green HL, Walker SJ, Gutin PH, Vilner L, Tabar V, Dominko T, Kane J, Wettstein PJ, Lanza RP, Studer L, Vrana KE, West MD (2002b) Parthenogenetic stem cells in nonhuman primates. Science 295:819

    CAS  PubMed  Google Scholar 

  • Clark AJ, Ferrier P, Aslam S, Burl S, Denning C, Wylie D, Ross A, de Sousa P, Wilmut I, Cui W (2003) Proliferative lifespan is conserved after nuclear transfer. Nat Cell Biol 5(6):535–538

    CAS  PubMed  Google Scholar 

  • Coffey PJ, Girman S, Wang SM, Hetherington L, Keegan DJ, Adamson P, Greenwood J, Lund RD (2002) Long-term preservation of cortically dependent visual function in RCS rats by transplantation. Nat Neurosci 5:53–56

    CAS  PubMed  Google Scholar 

  • Constantinescu D, Gray HL, Sammak PJ, Schatten GP, Csoka AB (2006) Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells 24(1):177–185

    CAS  PubMed  Google Scholar 

  • Cooke HJ, Smith BA (1986) Variability at the telomeres of the human X/Y pseudoautosomal region. Cold Spring Harb Symp Quant Biol 51 Pt1:213–219

    CAS  PubMed  Google Scholar 

  • Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S (1992) Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 11:1921–1929

    CAS  PubMed  Google Scholar 

  • Counter CM, Botelho FM, Wang P, Harley CB, Bacchetti S (1994) Stabilization of short telomeres and telomerase activity accompany immortalization of Epstein-Barr virus-transformed human B lymphocytes. J Virol 68:3410–3414

    CAS  PubMed  Google Scholar 

  • Coutts M, Keirstead HS. (2008) Stem cells for the treatment of spinal cord injury. Exp Neurol 209(2):368–77

    CAS  PubMed  Google Scholar 

  • Crabbe L, Verdun RE, Haggblom CI, Karlseder J (2004) Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306:1951–1953

    CAS  PubMed  Google Scholar 

  • Crabbe L, Jauch A, Naeger CM, Holtgreve-Grez H, Karlseder J (2007) Telomere dysfunction as a cause of genomic instability in Werner syndrome. Proc Natl Acad Sci USA 104:2205–2210

    CAS  PubMed  Google Scholar 

  • Cristofalo VJ (2005) SA beta Gal staining: biomarker or delusion. Exp Gerontol 40:836–838

    CAS  PubMed  Google Scholar 

  • Cristofalo VJ, Kabakjian J (1975) Lysosomal enzymes and aging in vitro: subcellular enzyme distribution and effect of hydrocortisone on cell life-span. Mech Ageing Dev 4:19–28

    CAS  PubMed  Google Scholar 

  • Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG, Beck JC (1998) Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci USA 95:10614–10619

    CAS  PubMed  Google Scholar 

  • D’Adda Di Fagagna F, 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 426:194–198

    PubMed  Google Scholar 

  • D’Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotech 24:1392–1401

    Google Scholar 

  • da Cruz L, Chen FK, Ahmado A, Greenwood J, Coffey P (2007) RPE transplantation and its role in retinal disease. Prog Retin Eye Res 26:598–635

    PubMed  Google Scholar 

  • D’Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, Vollrath D (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9:645–651

    PubMed  Google Scholar 

  • Da Silva MA, Yamada N, Clarke NM, Roach HI (2008) Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res Nov 4 [Epub ahead of print]

    Google Scholar 

  • DeCaprio JA, Ludlow JW, Figge J, Shew J-Y, Huang C-M, Lee W-H, Marsilio E, Paucha E, Livingston DM (1988) SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54:275–283

    CAS  PubMed  Google Scholar 

  • de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–2110

    PubMed  Google Scholar 

  • Dell’Orco RT, Mertens JG, Kruse PF (1973) Doubling potential, calendar time, and senescence of human diploid cells in culture. Exp Cell Res 77(1):36–360

    Google Scholar 

  • Di Micco R, Cicalese A, Fumagalli M, Dobreva M, Verrecchia A, Pelicci PG, di Fagagna F (2008) DNA damage response activation in mouse embryonic fibroblasts undergoing replicative senescence and following spontaneous immortalization. Cell Cycle 7:3601–3606

    PubMed  Google Scholar 

  • Ding SL, Shen CY (2008) Model of human aging: recent findings on Werner’s and Hutchinson-Gilford progeria syndromes. Clin Interv Aging 3:431–444

    CAS  PubMed  Google Scholar 

  • Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2004) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22:53–54

    CAS  PubMed  Google Scholar 

  • Effros RB, Allsopp R, Chiu C-P, Hausner MA, Hirji K, Wang L, Harley CB, Villeponteau B, West MD, Giorgi JV (1996) Shortened telomeres in the expanded CD28- CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. AIDS 10:F17–F22

    CAS  PubMed  Google Scholar 

  • Eller MS, Liao X, Liu S, Hanna K, Bäckvall H, Opresko PL, Bohr VA, Gilchrest BA (2006) A role for WRN in telomere-based DNA damage responses. Proc Natl Acad Sci USA 103:15073–15078

    CAS  PubMed  Google Scholar 

  • Epstein CJ, Martin GM, Schultz AI, Motulsky AG (1966) Werner’s syndrome: a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore) 45:177–221

    CAS  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    CAS  PubMed  Google Scholar 

  • Evans MJ, Gurer C, Loike JD, Wilmut I, Schnieke AE, Schon EA (1999) Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep. Nat Genet 23:90–93

    CAS  PubMed  Google Scholar 

  • Fauce SR, Jamieson BD, Chin AC, Mitsuyasu RT, Parish ST, Ng HL, Kitchen CM, Yang OO, Harley CB, Effros RB (2008) Telomerase-based pharmacologic enhancement of antiviral function of human CD8+ T lymphocytes. J Immunol 181:7400–7406

    CAS  PubMed  Google Scholar 

  • Feng J, Funk WD, Wang S-S, Weinrich SL, Avilion AA, Chiu C-P, Adams R, Chang E, Allsopp RC, Siyuan Le J-Y, West MD, Harley CB, Andrews WH, Greider CW, Villeponteau BV (1995) The RNA Component of Human Telomerase. Science 269:1236–1241

    CAS  PubMed  Google Scholar 

  • Forsyth NR, Evans AP, Shay JW, Wright WE (2003) Developmental differences in the immortalization of lung fibroblasts by telomerase. Aging Cell 2:235–243

    CAS  PubMed  Google Scholar 

  • Freberg CT, Dahl JA, Timoskainen S, Collas P (2007) Epigenetic reprogramming of OCT4 and NANOG regulatory regions by embryonal carcinoma cell extract. Mol Biol Cell 18:1543–1553

    CAS  PubMed  Google Scholar 

  • Friedman DM (2007) The Immortalists. HarperCollins Publishers, New York

    Google Scholar 

  • Friedman DS, O’Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572

    PubMed  Google Scholar 

  • Gallimore PH, Lecane PS, Roberts S, Rookes SM, Grand RJ, Parkhill J (1997) Adenovirus type 12 early region 1 B 54 K protein significantly extends the life span of normal mammalian cells in culture. J Virol 71:6629–6640

    CAS  PubMed  Google Scholar 

  • Garcia-Cao I, Garcia-Cao M, Martin-Caballero J, Criado LM, Klatt P, Flores JM, Weill JC, Blasco MA, Serrano M (2002) ‘‘Super p53’ mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 21:6225–6235

    CAS  PubMed  Google Scholar 

  • Genovese J, Cortes-Morichetti M, Chachques E, Frati G, Patel A, Chachques JC (2007) Cell based approaches for myocardial regeneration and artificial myocardium. Curr Stem Cell Res Ther 2:121–127

    CAS  PubMed  Google Scholar 

  • Girardi AJ, Jensen FC, Koprowski H (1965) SV40-induced transformation of human diploid cells: Crisis and recovery. J Cell Physiol 65:69–83

    CAS  PubMed  Google Scholar 

  • Gonzales-Suarez E, Samper E, Flores JM, Blasco MA (2000) Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat Genet 26:114–117

    Google Scholar 

  • Gonzales-Suarez E, Samper E, Ramirez A, Flores JM, Martin-Caballero J, Jorcano JL, Blasco MA (2001) Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J 20:2619–2630

    Google Scholar 

  • Green MR (1989) When the products of oncogenes and anti-oncogenes meet. Cell 56:1–3

    CAS  PubMed  Google Scholar 

  • Greider CW, Blackburn EH (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405–413

    CAS  PubMed  Google Scholar 

  • Greider CW, Blackburn EH (1987) The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell 51:887–898

    CAS  PubMed  Google Scholar 

  • Greider CW, Blackburn EH (1989) A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337:331–337

    CAS  PubMed  Google Scholar 

  • Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Mammalian telomeres end in a large duplex loop. Cell 97:503–514

    CAS  PubMed  Google Scholar 

  • Halliday TR, Adler K (eds) (1986) Reptiles & Amphibians. Torstar Books, p. 101

    Google Scholar 

  • Harley CB, Kim NW, Prowse KR, Weinrich SL, Hirsch KS, West MD, Bacchetti S, Hirte HW, Counter CM, Greider CW, Piatyszek MA, Wright WE, Shay JW (1994) Telomerase, Cell Immortality, and Cancer. Cold Spring Harbor Symposium on Quantitative Biology LIX:307–315 Cold Spring Harbor Press, Cold Spring Harbor, NY

    Google Scholar 

  • Harley, CB, Futcher, AB, Greider, CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    CAS  PubMed  Google Scholar 

  • Harrison DE, Astle CM, Delaittre JA (1978) Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging. J Exp Med 147:1526–1531

    CAS  PubMed  Google Scholar 

  • Haruta M (2005) Embryonic stem cells: potential source for ocular repair. Semin Ophthalmol 20:17–23

    PubMed  Google Scholar 

  • Hasenmaile S, Pawelec G, Wagner W (2003) A lack of telomeric non-reciprocal recombination (TENOR) may account for the premature proliferation blockade of Werner’s syndrome fibroblasts. Biogerontology 4:253–273

    CAS  PubMed  Google Scholar 

  • Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC (1990) Telomere reduction in human colorectal carcinoma and with ageing. Nature 346:866–868

    CAS  PubMed  Google Scholar 

  • Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    CAS  PubMed  Google Scholar 

  • Hayflick L (1968) Human cells and aging. Sci Am 218:32–37

    CAS  PubMed  Google Scholar 

  • Hayflick L (1992) Aging, longevity, and immortality in vitro. Exp Gerontol 27:363–368

    CAS  PubMed  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    CAS  PubMed  Google Scholar 

  • Henderson ER, Blackburn EH (1989) An overhanging 3’ terminus is a conserved feature of telomeres. Mol Cell Biol 9:345–348

    CAS  PubMed  Google Scholar 

  • Horikawa I, Chiang YJ, Patterson T, Feigenbaum L, Leem S-H, Michishita E, Larionov V, Hodes RJ, Barrett JC (2005) Differential cis-regulation of human versus mouse TERT gene expression in vivo: Identification of a human-specific repressive element. Proc Natl Acad Sci USA 102:18437–18442

    CAS  PubMed  Google Scholar 

  • Itahana K, Campisi J, Dimri, GP (2007) Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay. Methods Mol Biol 371:21–31

    CAS  PubMed  Google Scholar 

  • Jeyapalan JC, Ferreira M Sedivy JM Herbig U (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev 128:36–44

    CAS  PubMed  Google Scholar 

  • Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection Nat Genet 27:247–254

    CAS  Google Scholar 

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PLC, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2014

    CAS  PubMed  Google Scholar 

  • Klimanskaya I, Hipp J, Rezai KA, West M, Atala A, Lanza R (2004) Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells 6(3):217–245

    CAS  PubMed  Google Scholar 

  • Komatsumoto S, and Nara M (1995) Changes in the level of endothelin-1 with aging. Nippon Ronen Igakkai Zasshi 32:664–669

    Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Lanza RP, Cibelli JB, West MD (1999a) Human therapeutic cloning. Nat Med 5(9):975–977

    CAS  PubMed  Google Scholar 

  • Lanza RP, Cibelli JB, West MD (1999b) Prospects for the use of nuclear transfer in human transplantation. Nat Biotech 17(12):1171–1174

    CAS  Google Scholar 

  • Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, Mak J, Schertzer M, Chavez EE, Sawyer N, Lansdorp PM, West MD (2000) Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 288:665–669

    CAS  PubMed  Google Scholar 

  • Lanza RP, Cibelli JB, West MD, Dorff E, Tauer C, Green RM (2001) The ethical reasons for stem cell research. Science 292(5520):1299b

    Google Scholar 

  • Lanza RP, Chung HY, Yoo JJ, Wettstein PJ, Blackwell C, Borson N, Hofmeister E, Schuch G, Soker S, Moraes CT, West MD, Atala A (2002) Generation of histocompatible tissues using nuclear transplantation. Nat Biotech 20(7):689–696

    CAS  Google Scholar 

  • Lanza R, Moore MA, Wakayama T, Perry AC, Shieh J-H, Hendrikx J, Leri A, Chimenti S, Monsen A, Nurzynska D, West MD, Kajstura J, Anversa P (2004) Regeneration of infarcted heart with stem cells derived by nuclear transplantation. Circ Res 94(6):820–827

    CAS  PubMed  Google Scholar 

  • Lanza R, Shieh J-H, Wettstein PJ, Sweeney RW, Wu K, Weisz A, Borson N, Henderson B, West MD, Moore MAS (2005) Long-term bovine hematopoietic engraftment with clone-derived stem cells. Cloning Stem Cells 7(2):95–106

    CAS  PubMed  Google Scholar 

  • Le Couteur DG, Cogger VC, McCuskey RS, DE Cabo R, Smedsrød B, Sorensen KK, Warren A, Fraser R (2007) Age-related changes in the liver sinusoidal endothelium: a mechanism for dyslipidemia. Ann NY Acad Sci 1114:79–87

    Google Scholar 

  • Le Douarin NM (1984) Ontogeny of the peripheral nervous system from the neural crest and the placodes: a developmental model studied on the basis of the quail-chick chimaera system. Harvey Lect 1984–1985;80:137–186

    Google Scholar 

  • Le Maitre CL, Freemont AJ, Hoyland JA (2007) Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther 9:R45

    PubMed  Google Scholar 

  • Lee HW, Blasco MA, Gottlieb GJ, Horner JW 2nd, Greider CW, DePinho RA (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392:569–574

    CAS  PubMed  Google Scholar 

  • Li B, Jog SP, Reddy S, Comai L (2008) WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-mediated telomere shortening. Mol Cell Biol 28:1892–1904

    PubMed  Google Scholar 

  • Lillard-Wetherell K, Machwe A, Langland GT, Combs KA, Behbehani GK, Schonberg SA, German J, Turchi JJ, Orren DK, Groden J (2004) Association and regulation of the BLM helicase by the telomeric proteins TRF1 and TRF2. Hum Mol Genet 13:1919–1932

    CAS  PubMed  Google Scholar 

  • Liu D, O’Connor MS, Qin J, Songyang, Z (2004) Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J Biol Chem 279:51338–51342

    CAS  PubMed  Google Scholar 

  • Liu L, Bailey SM, Okuka M, Muñoz P, Li C, Zhou L, Wu C, Czerwiec E, Sandler L, Seyfang A, Blasco MA, Keefe DL (2007) Telomere lengthening early in development. Nat Cell Biol 9:1436–1441

    CAS  PubMed  Google Scholar 

  • Liu Y, Wang Y, Rusinol AE, Sinensky MS, Liu J, Shell SM, Zou Y (2008) Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation or prelamin A. FASEB J 22:603–611

    CAS  PubMed  Google Scholar 

  • Lombard DB, Beard C, Johnson B, Marciniak RA, Dausman J, Bronson R, Buhlmann JE, Lipman R, Curry R, Sharpe A, Jaenisch R, Guarente L (2000) Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Mol Cell Biol 20:3286–3291

    CAS  PubMed  Google Scholar 

  • Long DA, Mu W, Price KL, Johnson RJ (2005) Blood vessels and the aging kidney. Nephron Exp Nephrol 101:e95–e99

    PubMed  Google Scholar 

  • Lu SJ, Feng Q, Caballero S, Chen Y, Moore MA, Grant MB, Lanza, R (2007) Generation of functional hemangioblasts from human embryonic stem cells. Nat Methods 4:501–509

    CAS  PubMed  Google Scholar 

  • Lund RD, Adamson P, Sauve Y, Keegan DJ, Girman SV, Wang S, Winton H, Kanuga N, Kwan AS, Beauchene L, Zerbib A, Hetherington L, Couraud PO, Coffey P, Greenwood J (2001) Sub-retinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats. Proc Natl Acad Sci USA 98:9942–9947

    CAS  PubMed  Google Scholar 

  • Lund RD, Wang S, Klimanskaya I, Holmes T Ramos-Kelsey R, Lu B, Girman S, Bischoff N, Sauve Y, Lanza R (2006) Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 8:189–199

    CAS  PubMed  Google Scholar 

  • Lundblad V, Szostak JW (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57:633–643

    CAS  PubMed  Google Scholar 

  • Machwe A, Xiao L, Orren DK (2004) TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene 23:149–156

    CAS  PubMed  Google Scholar 

  • Martin GM (1981) Isolation of pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638

    CAS  PubMed  Google Scholar 

  • Matheu A, Pantoja C, Efeyan A, Criado LM, Martin-Caballero J, Flores JM, Klatt P, Serrano M (2004) Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging. Genes Dev 18:2736–2746

    CAS  PubMed  Google Scholar 

  • Matheu A, Maraver A, Klatt P, Flores I, Garcia-Cao I, Borras C, Flores JM, Vinã J, Blasco MA, Serrano M (2007) Delayed aging through damage protection by the Arf/p53 pathway. Nature 448:375–379

    CAS  PubMed  Google Scholar 

  • Matsunaga H, Handa JT, Aotaki-Keen A, Sherwood SW, West MD, Hjelmeland LM (1999) Beta-galactosidase histostochemistry and telomere loss in senescent retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 40:197–202

    CAS  PubMed  Google Scholar 

  • McKay R, Kittappa R (2008) Will stem cell biology generate new therapies for Parkinson’s disease? Neuron 58:659–661

    CAS  PubMed  Google Scholar 

  • McLaren A (1992) Embryology. The quest for immortality. Nature 359:482–483

    CAS  PubMed  Google Scholar 

  • McLaren A (2001) Mammalian germ cells: birth, sex, and immortality. Cell Struct Funct 26:119–122

    CAS  PubMed  Google Scholar 

  • McLeod DS, Taomoto M, Otsuji T, Green WR, Sunness JS, Lutty GA (2002) Quantifying changes in RPE and choroidal vasulature in eyes with age-related macular degeneration. Invest Ophthalmol Vis Sci 43:1986–1993

    PubMed  Google Scholar 

  • Meier A, Fiegler H, Muñoz P, Ellis P, Rigler D, Langford C, Blasco MA, Carter N, Jackson SP (2007) Spreading of mammalian DNA-damage response factors studied by ChIP-chip at damaged telomeres. EMBO J 26:2707–2718

    CAS  PubMed  Google Scholar 

  • Minamino T, and Komuro I (2008a) Role of telomeres in vascular senescence. Front Biosci 13:2971–2979

    CAS  PubMed  Google Scholar 

  • Minamino T, Komuro I (2008b) Vascular aging: insights from studies on cellular senescence, stem cell aging, and progeroid syndromes. Nat Clin Pract Cardiovasc Med 5:637–648

    CAS  PubMed  Google Scholar 

  • Mogford JE, Liu WR, Reid R, Chiu C-P, Said H, Chen SJ, Harley CB, Mustoe TA (2006) Adenoviral human telomerase reverse transcriptase dramatically improves ischemic wound healing without detrimental immune response in an aged rabbit model. Hum Gene Ther 17:651–660

    CAS  PubMed  Google Scholar 

  • Morgan R, Jarzabek V, Jaffe JP, Hecht BK, Hecht F, Sandberg AA (1986) Telomeric fusion in pre-T-cell acute lymphoblastic leukemia. Hum Genet 73:260–263

    CAS  PubMed  Google Scholar 

  • Morin GB (1989) The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59:521–529

    CAS  PubMed  Google Scholar 

  • Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, Wu JR (1988) A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 85:6622–6626

    CAS  PubMed  Google Scholar 

  • Muntoni A, Neumann AA, Hills M, Reddel RR (2008) Telomere elongation involves intra-molecular DNA replication in cells utilizing Alternative Lengthening of Telomeres. Hum Mol Genet 2008 Dec 18 [Epub ahead of print]

    Google Scholar 

  • Nagy A, Gertsenstein M, Vintersten K, Behringer R (eds) (2003) Manipulating the mouse embryo: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • Nakajima M, Hashimoto M, Wang F, Yamanaga K, Nakamura N, Uchida T, Yamanouchi K (1997) Aging decreases the production of PGI2 in rat aortic endothelial cells. Exp Gerontol 32:685–693

    CAS  PubMed  Google Scholar 

  • Nakamura AJ, Chiang YJ, Hathcock KS, Horikawa I, Sedelnikova OA, Hodes RJ, Bonner WM (2008) Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence. Epigenetics Chromatin 1:6

    PubMed  Google Scholar 

  • Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277:955–959

    CAS  PubMed  Google Scholar 

  • Neubert K, Haberland A, Kruse I, Wirth M, Schimke I (1997) The ratio of formation of prostacyclin/thromboxane A2 in HUVEC decreased in each subsequent passage. Prostaglandins 54:447–462

    CAS  PubMed  Google Scholar 

  • Niida H, Matsumoto T, Satoh H, Shiwa M, Tokutake Y, Furuichi Y, Shinkai, Y (1998) Severe growth defect in mouse cells lacking the telomerase RNA component. Nat Genet 19:203–206

    CAS  PubMed  Google Scholar 

  • Norrback KF, Hultdin M, Dahlenborg K, Osterman P, Carlsson R, Roos G (2001) Telomerase regulation and telomere dynamics in germinal centers. Eur J Haematol 67:309–317

    CAS  PubMed  Google Scholar 

  • Oikawa S, Kawanishi S (1999) Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett 453:365–368

    CAS  PubMed  Google Scholar 

  • Olovnikov AM (1971) Principles of marginotomy in template synthesis of polynucleotides. Doklady Akad Nauk SSSR 201:1496–1499

    CAS  Google Scholar 

  • Orren DK, Theodore S, Machwe A (2002) The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry 41:13483–13488

    CAS  PubMed  Google Scholar 

  • Prowse KR, Greider CW (1995) Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci USA 92(11):4818–4822

    CAS  PubMed  Google Scholar 

  • Rathjen J, Lake JA, Bettess MD, Washington JM, Chapman G, Rathjen PD (1999) Formation of a primitive ectoderm like cell population, EPL cells, from ES cells in response to biologically derived factors. J Cell Sci 112(Pt 5):601–612

    CAS  PubMed  Google Scholar 

  • Ray FA, Meyne J, Kraemer PM (1992) SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts. Mutat Res 284:265–273

    CAS  PubMed  Google Scholar 

  • Rea MA, Zhou L, Qin Q, Barrandon Y, Easley KW, Gungner SF, Phillips MA, Holland WS, Gumerlock PH, Rocke DM, Rice RH (2006) Spontaneous immortalization of human epidermal cells with naturally elevated telomerase. J Invest Dermatol 126:2507–2515

    CAS  PubMed  Google Scholar 

  • Robertson E, Bradley A, Kuehn M, Evans M. (1986) Germ-line transmission of genes into cultured pluripotent cells by retroviral vector. Nature 323(6087):445–448

    CAS  PubMed  Google Scholar 

  • Roy NS, Cleren C, Singh SK, Yang L, Beal MF, Goldman SA (2006) Functional emgraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat Med 12:1259–1268

    CAS  PubMed  Google Scholar 

  • Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M, Lansdorp PM (1999) Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med 190:157–167

    CAS  PubMed  Google Scholar 

  • Sato I, Kaji K, Morita I, Nagao M, Murota S (1993) Augmentation of endothelin-1, prostacyclin and thromboxane A2 secretion associated with in vitro ageing in cultured human embilical vein endothelial cells. Mech Ageing Dev 71:73–84

    CAS  PubMed  Google Scholar 

  • Scheidtmann KH, Haber A (1990) Simian virus 40 T antigen induces or activates a protein kinase which phosphorylates the transformation-associated protein p53. J Virol 64:672–679

    CAS  PubMed  Google Scholar 

  • Schneider EL, Mitsui Y (1976) The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA 73:3584–3588

    CAS  PubMed  Google Scholar 

  • Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Differentiation of immortal cells inhibits telomerase activity. Proc Natl Acad Sci USA 95:13726–13731

    CAS  Google Scholar 

  • Sharma HW, Sokoloski JA, Perez JR, Maltese JY, Sartorelli AC, Stein CA, Nichols G, Khaled Z, Telang NT, Narayanan R (1995) Differentiation of immortal cells inhibits telomerase activity. Proc Natl Acad Sci USA 92:12343–12346

    CAS  PubMed  Google Scholar 

  • Shay JW, Wright WE (1989) Quantitation of the frequency of immortalization of normal human diploid fibroblasts by SV40 large T-antigen. Exp Cell Res 184:109–118

    CAS  PubMed  Google Scholar 

  • Shay JW, West MD, Wright WE (1992) Re-expression of senescent markers in de-induced reversibly immortalized cells. Exp Gerontol 27:477–492

    CAS  PubMed  Google Scholar 

  • Shay JW, Wright WE, Werbin H (1993) Toward a molecular understanding of human breast cancer: a hypothesis. Breast Cancer Res Treat 25:83–94

    CAS  PubMed  Google Scholar 

  • Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE (1999) Analysis of telomere lengths in cloned sheep. Nature 399(6734):316–317

    CAS  PubMed  Google Scholar 

  • Shiga T, Shirasawa H, Shimizu K, Dezawa M, Masuda Y, Simizu B (1997) Normal human fibroblasts immortalized by introduction of human papillomavirus type 16 (HPV-16) E6-E7 genes. Microbiol Immunol 41:313–319

    CAS  PubMed  Google Scholar 

  • Slagboom PE, Droog S, Boomsma DI (1994) Genetic determination of telomere size in humans: A twin study of three age groups. Am J Hum Genet 55:876–882

    CAS  PubMed  Google Scholar 

  • Smith JR, Venable S, Roberts TW, Metter EJ, Monticone R, Schneider EL (2002) Relationship between in vivo age and in vitro aging: assessment of 669 cell cultures derived from members of the Baltimore Longitudinal Study of Aging. J Gerontol A Biol Sci Med Sci 57: B239–246

    PubMed  Google Scholar 

  • Spyridopoulos I, Dimmeler S (2007) Can telomere length predict cardiovascular risk? Lancet 365:81–82

    Google Scholar 

  • Stauffer BL, Westby CM, DeSouza CA (2008) Endothelin-1, aging, and hypertension. Curr Opin Cardiol 23:350–355

    PubMed  Google Scholar 

  • Stevens LC. (1980) Teratocarcinogenesis and spontaneous parthenogenesis in mice. Results Probl Cell Differ 11:265–274.

    CAS  PubMed  Google Scholar 

  • Suda Y, Suzuki M, Ikawa Y, Aizawa S (1987) Mouse embryonic stem cells exhibit indefinite proliferative potential. J Cell Physiol 133:197–201

    CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    CAS  PubMed  Google Scholar 

  • Takai H, Smogorzewska A, de Lange T (2003) DNA damage foci at dysfunctional telomeres. Curr Biol 13:1549–1556

    CAS  PubMed  Google Scholar 

  • Taranger CK, Noer A, Sørensen AL, Håkelien AM, Boquest AC, Collas P (2005) Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Mol Biol Cell 16:5719–5735

    CAS  PubMed  Google Scholar 

  • Terry DF, Nolan VG, Andersen SL, Perls TT, Cawthon R (2008) Association of longer telomeres with better health in centenarians. J Gerontol A Biol Sci Med Sci 63:809–812

    PubMed  Google Scholar 

  • Thomson JA, Itskovitx-Eldor J, Shapiro SS, Waknitz MA, Swiergierl JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    CAS  PubMed  Google Scholar 

  • Tokunaga O, Yamada T, Fan JL, Watanabe T (1991) Age-related decline in prostacyclin synthesis by human aortic endothelial cells: Qualitative and quantitative analysis. Am J Pathol 138:941–949

    CAS  PubMed  Google Scholar 

  • Tomas-Loba A, Flores I Fernandez-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borras C, Matheu A, Klatt P, Flores JM, Vina J, Serrano M, Blasco MA (2008) Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135:609–622

    CAS  PubMed  Google Scholar 

  • Toulouse A, Sullivan AM (2008) Progress in parkinson’s disease – where do we stand? Prog Neurobiol Jun 5 [Epub ahead of print]

    Google Scholar 

  • Toussaint O, Medrano EE, von Zglinicki T (2000) Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol 35:927–945

    CAS  PubMed  Google Scholar 

  • Tsonis PA. (2008) Stem cells and blastema cells. Curr Stem Cell Res Ther 3(1):53–54

    CAS  PubMed  Google Scholar 

  • Umemura T, Soga J, Hidaka T, Takemoto H, Nakamura S, Jitsuiki D, Nishioka K, Goto C, Teragawa H, Yoshizumi M, Chayama K, Higashi Y (2008) Aging and hypertension are independent risk factors for reduced number of circulating endothelial progenitor cells. Am J Hypertens 21:1203–1209

    CAS  PubMed  Google Scholar 

  • Ungewitter E and Scrable H (2008) Antagonistic pleiotropy and p53. Mech Ageing Dev Jul 1 [Epub ahead of print]

    Google Scholar 

  • Vickers M, Brown GC, Cologne JB Kyoizumi S (2000) Modelling haemopoietic stem cell division by analysis of mutant red cells. Br J Haematol 110:54–62

    CAS  PubMed  Google Scholar 

  • von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27:339–344

    Google Scholar 

  • Vulliamy TJ, Knight SW, Mason PJ, Dokal I (2001a) Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenital. Blood Cells Mol Dis 27:353–357

    CAS  PubMed  Google Scholar 

  • Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001b) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenital. Nature 413:432–435

    CAS  PubMed  Google Scholar 

  • Wakayama T, Shinkai Y, Tamashiro KL, Niida H, Blanshard DC, Ogura A, Tanemura K, Tachibana M, Perry AC, Colgan DF, Mombaerts P, Yanagimachi R (2000) Cloning of mice to six generations. Nature 407(6802):318–319

    CAS  PubMed  Google Scholar 

  • Walen KH, Arnstein P (1986) Induction of tumorigenesis and chromosomal abnormalities in human amniocytes infected with simian virus 40 and Kirsten sarcoma virus. In Vitro Cell Dev Biol 22:57–65

    CAS  PubMed  Google Scholar 

  • Wang RC, Smogorzewska A, de Lange T (2004) Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119:355–368

    CAS  PubMed  Google Scholar 

  • Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239:197–201

    CAS  PubMed  Google Scholar 

  • Weismann A (1891) Essays upon heredity and kindred biological problems Vol I. Clarendon Press

    Google Scholar 

  • West MD (1994) The cellular and molecular biology of skin aging. Arch Dermatol 130:87–95

    CAS  PubMed  Google Scholar 

  • West MD (2003) The immortal cell. Doubleday, New York

    Google Scholar 

  • West MD, Pereira-Smith OM, Smith JR (1989) Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity. Exp Cell Res 184:138–147

    CAS  PubMed  Google Scholar 

  • West MD, Shay JW, Wright WE, Linskens MHK (1996) Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence. Exp Gerontol 31:175–193

    CAS  PubMed  Google Scholar 

  • West MD, Sargent RG, Long J, Brown C, Chu J-S, Kessler S, Derugin N, Sampathkumar J, Burrows C, Vaziri H, Williams R, Chapman KB, Larocca D, Loring JF, Murai J (2008) The ACTCellerate Initiative: large-scale combinatorial cloning of novel human embryonic stem cell derivatives. Reg Med 3(3):287–308

    CAS  Google Scholar 

  • West MD, Mason C (2007) Mapping the human embryome:1 to 10e13 and all the cells in between. Reg Med 2(4):329–333

    CAS  Google Scholar 

  • Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385(6619):810–813

    CAS  PubMed  Google Scholar 

  • Wright WE, Hayflick L (1975) Nuclear control of cellular aging demonstrated by hybridization of anucleate and whole cultured normal human fibroblasts. Exp Cell Res 96:133–121

    Google Scholar 

  • Wright WE, Pereira-Smith OM, Shay JW (1989) Reversible cellular senescence: Implications for immortalization of normal human diploid fibroblasts. Mol Cell Biol 9:3088–3092

    CAS  PubMed  Google Scholar 

  • Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW (1996) Telomerase activity in human germline and embryonic tissues and cells. Dev Genet 18:173–179

    CAS  PubMed  Google Scholar 

  • Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH (2006) Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart Cell 127:1137–1150

    CAS  Google Scholar 

  • Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, Wynford-Thomas D, Faragher RG, Kipling D (2000) Telomerase prevents the accelerated cell aging of Werner syndrome fibroblasts. Nat Genet 24:16–17

    CAS  PubMed  Google Scholar 

  • Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H (2005) Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 66:276–85

    CAS  PubMed  Google Scholar 

  • Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, Yamamoto H, Ide T, Utakoji T (1996) Telomerase activity in normal human epithelial cells Oncogene 13:433–439

    CAS  Google Scholar 

  • Yavuz BB, Yavuz B, Sener DD, Cankurtaran M, Halil M, Ulger Z, Nazli N, Kabakci G, Aytemir K, Tokgozoglu L, Oto A, Ariogul S (2008) Advanced age is associated with endothelial dysfunction in healthy elderly subjects. Gerontology 54:153–156

    CAS  PubMed  Google Scholar 

  • Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD (1996) Positional cloning of the Werner’s syndrome gene. Science 272:258–262

    CAS  PubMed  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    CAS  PubMed  Google Scholar 

  • Zhang X, Bok D (1998) Transplantation of retinal pigment epithelial cells and immune response in the subretinal space. Invest Ophthalmol Vis Sci 39:1021–1027

    CAS  PubMed  Google Scholar 

  • Zhong Z, Deane R, Ali Z, Parisi M, Shapovalov Y, O’Banion MK, Stojanovic K, Sagare A, Boillee S, Cleveland DW, Zlokovic BV (2008) ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 11:420–422

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CEO, BioTime, Inc. and Embryome Sciences, Inc., Alameda, CA, USA

    Michael D. West (CEO)

Authors
  1. Michael D. West
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael D. West .

Editor information

Editors and Affiliations

  1. Intervene Biomedical, LLC, Box 478, Norco, CA, 92860, USA

    Gregory M. Fahy

  2. BioTime, Inc., 1301 Harbor Bay Parkway, Alameda, CA, 94502, USA

    Michael D. West

  3. Institute of Molecular Biology Department of Chemistry and Biochemistry Young Hall, University of California, Los Angeles, CA, 90095-1569, USA

    L. Stephen Coles

  4. Critical Care Research, Inc., 10743 Civic Center Drive, Rancho Cucamonga, CA, 91730, USA

    Steven B. Harris

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

West, M.D. (2010). Embryonic Stem Cells: Prospects of Regenerative Medicine for the Treatment of Human Aging. In: Fahy, G.M., West, M.D., Coles, L.S., Harris, S.B. (eds) The Future of Aging. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3999-6_14

Download citation

Publish with us

Policies and ethics

Search

Navigation