Human Genetic Disorders That Feature Premature Onset and Accelerated Progression of Biological Aging

  • Samuel Goldstein

Abstract

Despite a burgeoning number of recent investigations and increasingly rigorous scrutiny, a universally acceptable definition of normal biological aging is still not available. The origins of senescence remain enigmatic, and little agreement exists regarding its true nature. While most would accept as genuine aging phenomena the diverse processes of hair graying, wrinkling of skin, and arteriosclerosis, they would, on the other hand, reserve embryogenesis, somatic growth, and pubescence for development. Both kinds of phenomena are clearly time-dependent, but the interface between them is often blurred (Goldstein, S., 1971a). The conceptual difficulty is exemplified by the frequent juxtaposition of involution and new development, even at early and middle stages of the life span (Saunders and Fallon, 1966). Cogent examples are the placenta vs. the fetus during gestation and the replacement of deciduous teeth by permanent dentition during infancy. During childhood, atrophy of the thymus occurs when virtually all other organs are growing and maturing, while the menopausal ovary involutes relatively abruptly in comparison with other organs in the middle-aged female. One could invoke examples of involution at the molecular level such as the loss during fetal life of various proteins including ϒ-hemoglobin, carcinoembryonic antigen, α-fetoprotein, and others (Gold, 1971). In short, attempts to delineate the point at which development is succeeded by aging may be futile, since both processes probably operate along the same continuum.

Keywords

Estrogen Dementia Radium Pancreatitis Anemia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alberti, K. G., Young, J. D., and Hockaday, T. O., 1974, Werner’s syndrome: Metabolic observations, Proc. R. Soc. Med. 67:36–38.PubMedGoogle Scholar
  2. Alton, D. J., McDonald, P., and Reilly, B. J., 1972, Cockayne’s syndrome: A report of three cases, Radiology 102:403–406.PubMedGoogle Scholar
  3. Ammann, A. J., Cain, W. A., Ishizaka, K., Hong, R., and Good, R. A., 1969, Immunoglobulin E deficiency in ataxia-telangiectasia, N. Engl. J. Med. 281:469–472.PubMedGoogle Scholar
  4. Andres, W., Pozefsky, T., Swerdloff, R. S., and Tobin, J. D., 1975, Effect of aging on carbohydrate metabolism, Adv. Metab. Disord. Suppl. 1:349–355.Google Scholar
  5. Atkins, L., 1954, Progeria: Report of a case with post-mortem findings, N. Engl. J. Med. 250:1065–1069.PubMedGoogle Scholar
  6. Bach, F. H., and van Rood, J. J., 1976, The major histocompatibility complex: Genetics and biology, N. Engl. J. Med. 295: 806–813, 872-878, 927-936.PubMedGoogle Scholar
  7. Balci, S., Say, B., and Kinik, E., 1970, Werner’s syndrome, Turk. J. Pediatr. 12:89–97.PubMedGoogle Scholar
  8. Benditt, E. P., and Benditt, J. M., 1973, Evidence for a monoclonal origin of human atherosclerotic plaques, Proc. Natl. Acad. Sci. U.S.A. 70:1753–1756.PubMedGoogle Scholar
  9. Bhakoo, O. N., Garg, S. K., and Sehgal, V. N., 1965, Progeria with unusual ocular manifestations: Report of a case with a review of the literature, Indian Pediatr. 2:164–169.PubMedGoogle Scholar
  10. Bingham, H. G., and Anderson, P. G., 1970, Coverage of cutaneous ulcers in Werner’s syndrome, Acta Derm.-Venereol. 50:237–239.PubMedGoogle Scholar
  11. Blinstrub, R. W., Lehman, R., and Steinberg, T. H., 1964, Poikiloderma congenitale: Report of two cases, Arch. Dermatol. 89:659–664.PubMedGoogle Scholar
  12. Blizzard, R. M., 1965, Dwarfism, in: Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence (L. Wilkins, ed.), pp. 160–194, Charles C. Thomas, Springfield, Illinois.Google Scholar
  13. Block, B., and Stauffer, H., 1929, Skin diseases of endocrine system (dyshormonal dermatoses): Poikiloderma-like changes in connection with underdevelopment of the sexual glands and dystrophia adiposogenitalis, Arch. Dermatol. Syphilol. 19:22–34.Google Scholar
  14. Boder, E., and Sedgwick, R. P., 1958, Ataxia-telangiectasia: A familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection, Pediatrics 21:526–554.PubMedGoogle Scholar
  15. Bottomley, W. K., and Box, J. M., 1976, Dental anomalies in the Rothmund-Thomson syndrome: Report of a case, Oral Surg. 4:321–326.Google Scholar
  16. Boué, A., Boué, J., Cure, S., Deluchat, C., and Perraudin, N., 1975, In vitro cultivation of cells from aneuploid human embryos: Initiation of cell lines and longevity of the culture, In Vitro 11:409–413.PubMedGoogle Scholar
  17. Boyd, M. W. J., and Grant, A. P., 1959, Werner’s syndrome (progeria of the adult): Further pathological and biochemical observations, Br. Med. J. 2:920–925.PubMedGoogle Scholar
  18. Bradley, M. O., Erickson, L. C., and Kohn, K. W., 1976, Normal DNA strand rejoining and absence of DNA crosslinking in progeroid and aging human cells, Mutat. Res. 37:279–292.PubMedGoogle Scholar
  19. Brautbar, C., Pellegrino, M. A., Ferrone, S., Reisfeld, R. A., Payne, R., and Hayflick, L., 1973, Fate of HL-A antigens in aging cultured human diploid cell strains. II. Quantitative absorption studies, Exp. Cell Res. 78:367–375.PubMedGoogle Scholar
  20. Bristow, J. H., 1973, Werner’s syndrome: Clinical features and cataract surgery, S. Afr. Med. J. 47:566–569.PubMedGoogle Scholar
  21. Brodrick, J. D., and Dark, A. J., 1973, Corneal dystrophy in Cockayne’s syndrome, Br. J. Opthalmol. 57:391–399.Google Scholar
  22. Bullock, J. D., and Howard, R.O., 1973, Werner’s syndrome, Arch. Ophthalmol. 90:53–56.PubMedGoogle Scholar
  23. Burch, P. R. J., and Milunsky, A., 1969, Early-onset diabetes mellitus in general and Down’s syndrome populations: Genetics, etiology, and pathogenesis, Lancet 1:554–558.PubMedGoogle Scholar
  24. Burnet, F. M., 1974, Intrinsic Mutagenesis: A Genetic Approach to Aging, John Wiley & Sons, New York.Google Scholar
  25. Burnett, J. W., 1968, Werner’s syndrome, South. Med. J. 61:207–209.PubMedGoogle Scholar
  26. Cahill, G. F., 1975, Disorders of carbohydrate metabolism, in: Textbook of Medicine (P. B. Beeson and W. McDermott, eds.), pp. 1599-1619, W. B. Saunders Co., Philadelphia. Cahill, G. F., Etzwiler, D. D., and Freinkel, N., 1976, “Control” and diabetes, N. Engl. J. Med. 294:1004–1005.Google Scholar
  27. Carr, D. H., 1975, Cytogenetics and the pathologist, Pathobiol. Annu. 10:93–144.Google Scholar
  28. Chaganti, R. S. K., Schonberg, S., and German, J., 1974, A manyfold increase in sister chromatid exchanges in Bloom’s syndrome lymphocytes, Proc. Natl. Acad. Sci. U.S.A. 71:4508–4512.PubMedGoogle Scholar
  29. Childs, B., and Der Kaloustian, V. M., 1968, Genetic heterogeneity, N. Engl. J. Med. 279: 1205–1212, 1267-1279.PubMedGoogle Scholar
  30. Cleaver, J. E., 1970, DNA damage and repair in light-sensitive human skin disease, J. Invest. Dermatol. 54:181–195.PubMedGoogle Scholar
  31. Cleaver, J. E., and Bootsma, D., 1975, Xeroderma pigmentosum: Biochemical and genetic characteristics, Annu. Rev. Genet. 9:19–38.PubMedGoogle Scholar
  32. Cleaver, J. E., Bootsma, D., and Friedberg, E., 1975, Human diseases with genetically altered DNA repair processes, Genetics 79:215–225.PubMedGoogle Scholar
  33. Cockayne, E. A., 1936, Dwarfism with retinal atrophy and deafness, Arch. Dis. Child. 11:1–8.PubMedGoogle Scholar
  34. Cohen, M. M., Shaham, M., Dagan, J., Shmueli, E., and Kohn, G., 1975, Cytogenetic investigations in families with ataxia-telangiectasia, Cytogenet. Cell Genet. 15:338–356.PubMedGoogle Scholar
  35. Cole, H. N., Giffen, H. K., Simmons, J. T., and Stroud, G. M., III, 1945, Congenital cataracts in sisters with congential ectoderma dysplasia, J. Am. Med. Assoc. 129:723–728.Google Scholar
  36. Coles, W. H., 1969, Ocular manifestations of Cockayne’s syndrome, Am. J. Ophthalmol. 67:762–764.PubMedGoogle Scholar
  37. Comfort, A., 1964, Ageing: The Biology of Senescence, Holt, Rinehart & Winston, New York.Google Scholar
  38. Comfort, A., 1969, Test-battery to measure ageing-rate in man, Lancet 2:1411–1415.PubMedGoogle Scholar
  39. Cotton, R. B., Keats, T. E., and McCoy, E. E., 1970, Abnormal blood glucose regulation in Cockayne’s syndrome, Pediatrics 46:54–60.PubMedGoogle Scholar
  40. Cox, R. P., 1974, Cell Communication, John Wiley & Sons, New York.Google Scholar
  41. Crapper, D. R., Dalton, A. J., Skopitz, M., Scott, J. W., and Hachinski, V. C., 1975, Alzheimer degeneration in Down syndrome: Electrophysiologic alterations and histopathologic findings, Arch. Neurol. 33:618–623.Google Scholar
  42. Creutzfeldt, W., Kobberling, J., and Neel, J. V. (eds.), 1975, The Genetics of Diabetes Mellitus, Springer-Verlag, New York.Google Scholar
  43. Cristofalo, V. J., 1972, Animal cell cultures as a model system for the study of aging, Adv. Gerontol. Res. 4:45–79.Google Scholar
  44. Crome, L., and Kanjilal, G. C., 1971, Cockayne’s syndrome: Case report, J. Neurol. Neurosurg. Psychiatry 34:171–178.PubMedGoogle Scholar
  45. Cunliffe, P. N., Mann, J. R., Cameron, A. H., Roberts, K. D., and Ward, H. W. C., 1975, Radio sensitivity in ataxia telangiectasia, Br. J. Radiol. 48:374–376.Google Scholar
  46. Dalton, A. J., Crapper, D. R., and Schlotterer, G. R., 1974, Alzheimer’s disease in Down’s syndrome: Visual retention deficits, Cortex 10:366–377.PubMedGoogle Scholar
  47. Danes, B. S., 1971, Progeria: A cell culture study on aging, J. Clin. Invest. 50:2000–2003.PubMedGoogle Scholar
  48. DeBusk, F. L., 1972, The Hutchinson-Gilford progeria syndrome: Report of four cases and review of the literature, J. Pediatr. 80(Part 2):695–724.Google Scholar
  49. Degreef, H., 1971, The Werner syndrome, Dermatologica 142:45–49.PubMedGoogle Scholar
  50. Diem, E., 1975, The Rothmund-Thomson syndrome: A case report, Hautarzt 26:425–429.PubMedGoogle Scholar
  51. Down, J. L. H., 1866, Observations on ethnic classification of idiots, Clin. Lect. Rep. London Hosp. 3:259–262.Google Scholar
  52. Driban, N. E., and Bertranou, E. G., 1975, Adult progeria (Werner’s syndrome), Med. Cutanea 3:213–222.Google Scholar
  53. Elmore, E., and Swift, M., 1976a, Growth of cultured cells from patients with Fanconi’s anemia, J. Cell. Physiol. 87: 229–234.Google Scholar
  54. Elmore, E., and Swift, M., 1976b, Growth of cultured cells from patients with ataxiatelangiectasia, J. Cell. Physiol. 89: 429–432.PubMedGoogle Scholar
  55. Engle, E., and Forbes, A. P. 1965, Cytogenetic and clinical findings in 48 patients with congenitally defective or absent ovaries, Medicine (Baltimore) 44:135–164.Google Scholar
  56. Epstein, C. J., Martin, G. M., Schultz, A. L., and Motulsky, A. G., 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.Google Scholar
  57. Epstein, J., Williams, J. R., and Little, J. B., 1973, Deficient DNA repair in human progeroid cells, Proc. Natl. Acad. Sci. U.S.A. 70:977–981.PubMedGoogle Scholar
  58. Epstein, J., Williams, J. R., and Little, J. B., 1974, Rate of DNA repair in progeric and normal human fibroblasts, Biochem. Biophys. Res. Commun. 59:850–856.PubMedGoogle Scholar
  59. Fajans, S. S., Floyd, J. C., Tattersall, R. B., Williamson, J. R., Pek, S., and Taylor C. I., 1976, The various faces of diabetes in the young, Arch. Intern. Med. 136:194–202.PubMedGoogle Scholar
  60. Faye, I., Ruscher, H., Marchand, J. P., Bloc, G., and Toure, M. F., 1973, A case of Werner’s syndrome, Bull. Soc. Med. Afr. Noire Lang. Fr. 18:564–566.PubMedGoogle Scholar
  61. Feigin, R. D., Vietti, T. J., Wyatt, R. G., Kaufman, D. G., and Smith, C. H., 1970, Ataxia telangiectasia with granulocytopenia, J. Pediatr. 77:431–438.PubMedGoogle Scholar
  62. Feingold, M., and Kidd, R., 1971, Progeria and scleroderma in infancy, Am. J. Dis. Child. 122:61–62.PubMedGoogle Scholar
  63. Felig, P., Wahren, J., Sherwin, R., and Hendler, R., 1976, Insulin, glucagon, and somatostatin in normal physiology and diabetes mellitus, Diabetes 25:1091–1099.PubMedGoogle Scholar
  64. Ferrari-Sacco, A., Carolei, P., Emanuele, B., Marasso, A., and Marengo, G., 1972, Etiopathogenetic, clinical and anatomo-histological notes on a very rare form of congenital anomaly (Werner’s syndrome or Rothmund-Thomson syndrome) associated with pulmonary tuberculosis, Minerva Med. 63:2563–2573.PubMedGoogle Scholar
  65. Finkelberg, R., 1976, Studies on cells from patients with Fanconi’s anemia, Ph.D. thesis, University of Toronto.Google Scholar
  66. Fleischmajer, R., and Nedwich, A., 1973a, Progeria (Hutchinson-Gilford), Arch. Dermatol. 107: 253–258.PubMedGoogle Scholar
  67. Fleischmajer, R., and Nedwich, A., 1973b, Werner’s syndrome, Am. J. Med. 54: 111–118.PubMedGoogle Scholar
  68. Forbes, A. P., and Engel, E., 1963, The high incidence of diabetes mellitus in 41 patients with onadal dysgenesis and their close relatives, Metabolism 12:428–439.PubMedGoogle Scholar
  69. Ford, C. E., Kones, K. W., Polani, P. E., DeAlmeida, J. C., and Briggs, J. H., 1959, A sex chromosome anomaly in a case of gonadal dysgenesis (Turner’s syndrome) Lancet 1:711.PubMedGoogle Scholar
  70. Franceschetti, A., 1953, Les dysplasies ectodermiques et les syndromes héréditaires apparantes, Dermatologica 106:129–156.PubMedGoogle Scholar
  71. Franks, L. M., 1972, The ultrastructure of tissue culture cells, Symp. Biol. Hung. 14:31–35.Google Scholar
  72. Fraser, G. R., and Friedmann, A. I., 1967, The Causes of Blindness in Childhood: A Study of 776 Children with Severe Visual Handicaps, Johns Hopkins University Press, Baltimore.Google Scholar
  73. Fratontoni, J. C., Hall, C. W., and Neufeld, E. F., 1968, Hurler and Hunter syndromes: Mutual correction of the defect in cultured fibroblasts, Science 162:570–572.Google Scholar
  74. Frenkel, G., 1970, Mucosal atrophy with special reference to the Werner syndrome, Dtsch. Zahnaerztl. Z. 25:1026–1029.PubMedGoogle Scholar
  75. Friedman, J. M., and Fialkow, P. J., 1976, Cell marker studies of human tumorigenesis, Transplant. Rev. 28:17–33.PubMedGoogle Scholar
  76. Fujimoto, W. Y., Green, M. L., and Seegmiller, J. E., 1969, Cockayne’s syndrome: Report of a case with hyperlipoproteinemia, hyperinsulinemia, renal disease, and normal growth hormone, J. Pediatr. 75:881–884.PubMedGoogle Scholar
  77. Gabr, M., Hashem, N., Hashem, F., Fahmi, A., and Safouh, M., 1960, Progeria, a pathologic study, J. Pediatr. 57:70–77.PubMedGoogle Scholar
  78. Galloway, S. M., and Evans, H. J., 1975, Sister chromatid exchange in human chromosomes from normal individuals and patients with ataxia telangiectasia, Cytogenet. Cell Genet. 15:17–29.PubMedGoogle Scholar
  79. Gardner, D. G., and Majka, M., 1969, The early formation of irregular secondary dentine in progeria, Oral Surg. Oral Med. and Oral Pathol. 28:877–884.Google Scholar
  80. Gerald, P. S., 1976, Current concepts in genetics—Sex chromosome disorders, N. Engl. J. Med. 294:706–708.PubMedGoogle Scholar
  81. German, J., 1974, Chromosomes and Cancer, John Wiley & Sons, New York.Google Scholar
  82. Gershon, D., and Gershon, H., 1976, An evaluation of the “error catastrophe” theory of ageing in the light of recent experimental results, Gerontology 22:212–219.PubMedGoogle Scholar
  83. Ghosh, S., and Berry, A. M., 1973, Progeria—A follow up of 8 years, Indian Pediatr. 10:45.PubMedGoogle Scholar
  84. Ghosh, S., and Varma, K. P. S., 1964, Progeria: Report of a case with review of the literature, Indian Pediatr. 1:146–155.PubMedGoogle Scholar
  85. Giacomini, F., and Rizzi, B., 1968, Considerations on the osteogenic healing process in a case of true progeria, Arch. Ortop. 81:379–389.PubMedGoogle Scholar
  86. Gibbs, D. D., 1967, Werner’s syndrome (progeria of the adult), Proc. R. Soc. Med. 60:135–136.PubMedGoogle Scholar
  87. Gilford, H., 1897, On the condition of mixed premature and immature development, Trans. Med.-Chir. Soc. Edinburgh 80:17–45.Google Scholar
  88. Gilkes, J. J., Sharvill, D. E., and Wells, R. S., 1974, The premature ageing syndromes: Report of eight cases and description of a new entity named metageria, Br. J. Dermatol. 91:243–262.PubMedGoogle Scholar
  89. Ginsberg-Fellner, F., and Knittle, J. L., 1973, Adipose tissue cellularity and metabolism in newly diagnosed juvenile diabetics, Diabetes 22:528–536.PubMedGoogle Scholar
  90. Goetz, I., Roberts, E., and Comings, D. E., 1975, Fibroblasts in Huntington’s disease, N. Engl. J. Med. 293:1225–1227.PubMedGoogle Scholar
  91. Gold, P., 1971, Antigenic reversion in human cancer, Annu. Rev. Med. 22:85–94.PubMedGoogle Scholar
  92. Goldstein, D. E., Drash, A., Gibbs, J., and Blizzard, R. M., 1970, Diabetes mellitus: The incidence of circulating antibodies against thyroid, gastric and adrenal tissue, J. Pediatr. 77:304–306.PubMedGoogle Scholar
  93. Goldstein, S., 1969, Lifespan of cultured cells in progeria, Lancet 1:424.PubMedGoogle Scholar
  94. Goldstein, S., 1971a, The biology of aging, N. Engl. J. Med. 285: 1120–1129.PubMedGoogle Scholar
  95. Goldstein, S., 1971b, On the pathogenesis of diabetes mellitus and its relationship to biological aging, Humangenetik 12: 83.PubMedGoogle Scholar
  96. Goldstein, S., 1971c, The role of DNA repair in aging of cultured fibroblasts from Xeroderma pigmentosum and normals, Proc. Soc. Exp. Biol. Med. 137: 730–734.Google Scholar
  97. Goldstein, S., 1978a, Senescence. I. Hormones and aging, in: Metabolic Basis of Endrocrinology (Degroot, Martins, Potts, Nelson, Winegrad, Odell, Steinberger, and Cahill, eds.), Grune and Stratton, New York (in press).Google Scholar
  98. Goldstein, S., 19786, Senescence. II. General and cellular aging, in: Metabolic Basis of Endocrinology (Degroot, Martins, Potts, Nelson, Winegrad, Odell, Steinberger, and Cahill, eds.), Grune and Stratton, New York (in press).Google Scholar
  99. Goldstein, S., and Moerman, E., 1975a, Heat-labile enzymes in skin fibroblasts from subjects with progeria, N. Engl. J. Med. 292: 1305–1309.PubMedGoogle Scholar
  100. Goldstein, S., and Moerman, E. J., 1975b, Heat-labile enzymes in Werner’s syndrome fibroblasts, Nature (London) 255: 159.Google Scholar
  101. Goldstein, S., and Moerman, E. J., 1976a, The Hutchinson—Gilford (progeria) syndrome: Heat-lability of enzymes, in red blood cells in a family, Clin. Res. 24:668A.Google Scholar
  102. Goldstein, S., and Moerman, E. J., 1916b, Defective proteins in normal and abnormal human fibroblasts during aging in vitro, Interdiscip. Top. Gerontol. 10: 24–43.Google Scholar
  103. Goldstein, S., and Niewiarowski, S., 1976, Increased procoagulant activity in cultured fibroblasts from progeria and Werner’s syndromes of premature ageing, Nature (London) 260:711–713.Google Scholar
  104. Goldstein, S., and Singal, D. P., 1974, Alteration of fibroblast gene products in vitro from a subject with Werner’s syndrome, Nature (London) 251:719–721.Google Scholar
  105. Goldstein, S., and Trieman, G., 1975, Glucose consumption by early and late-passage diploid human fibroblasts during growth and stationary phase, Experientia 31:177–180.PubMedGoogle Scholar
  106. Goldstein, S., Littlefield, J. W., and Soeldner, J. S., 1969, Diabetes mellitus and aging: Diminished plating efficiency of cultured human fibroblasts, Proc. Natl. Acad. Sci. U.S.A. 64:155–160.PubMedGoogle Scholar
  107. Goldstein, S., Moerman, E. J., Soeldner, J. S., Gleason, R. E., and Barnett, D. M., 1974, Diabetes mellitus and prediabetes: Decreased replicative capacity of cultured fibroblasts, J. Clin. Invest. 53: 27a–27b.Google Scholar
  108. Goldstein, S., Niewiarowski, S., and Singal, D. P., 1975, Pathological implications of cell aging in vitro, Fed. Proc. Fed. Am. Soc. Exp. Biol. 34:56–63.Google Scholar
  109. Goldstein, S., Stotland, D., and Cordeiro, R. A. J., 1976, Decreased proteolysis and increased amino acid efflux in aging human fibroblasts. Mech. Agein Dev. 5:221–233.Google Scholar
  110. Goldstein, S., Moerman, E. J., Soeldner, J. S., Gleason, R. E., and Barnett, D. M., 1978, Chronologic age and physiologic status: Effect on replicative lifespan of cultured human fibroblasts from diabetic, prediabetic and normal donors, Science (in press).Google Scholar
  111. Good, R. A., and Yunis, E., 1974, Association of autoimmunity, immunodeficiency and aging in man, rabbits and mice, Fed. Proc. Fed. Am. Soc. Exp. Biol. 33:2040–2050.Google Scholar
  112. Gotoff, S. P., Amirmokri, E., and Liebner, E. J., 1967, Ataxia telangiectasia, neoplasia, untoward response to X-irradiation, and tuberous sclerosis, Am. J. Dis. Child. 114:617–625.PubMedGoogle Scholar
  113. Gottron, H., 1940, Familiare akrogerie, Arch. Dermatol. Syphilol. 181:571–583.Google Scholar
  114. Greene, M. L., Glueck, C. J., Fujimoto, W. Y., and Seegmiller, J. E., 1970, Benign symmetric lipomatosis (Launois-Bensaude adenolipomatosis) with gout and hyperlipoproteinemia, Am. J. Med. 48: 239–246.PubMedGoogle Scholar
  115. Griffin, J. E., Punyashthiti, K., and Wilson, J. D., 1976, Dihydrotestosterone binding by cultured human fibroblasts: Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance, J. Clin. Invest. 57:1342–1351.PubMedGoogle Scholar
  116. Grunebaum, M., 1973, Progeria, Postgrad. Med. 53:221–222.PubMedGoogle Scholar
  117. Gsell, O., and Haensch, G., 1971, Werner’s syndrome: A case report on premature aging, Schweiz. Med. Wochenschr. 101:418–421.PubMedGoogle Scholar
  118. Haerer, A. F., Jackson, J. F., and Evers, C. G., 1969, Ataxia-telangiectasia with gastric adenocarcinoma, J. Am. Med. Assoc. 210:1884–1887.Google Scholar
  119. Hall, B. D., Berg, B. O., Rudolph, R. S., and Epstein, C. J., 1974, Pseudoprogeria-Hallermann-Streiff (PHS) syndrome, Birth Defects: Orig. Artic. Ser. 10:137–146.Google Scholar
  120. Hamlin, C. R., Kohn, R. R., and Luschin, J. H., 1975, Apparent accelerated aging of human collagen in diabetes mellitus, Diabetes 24:902–904.PubMedGoogle Scholar
  121. Harnden, D. G., 1974, Ataxia telangiectasia syndrome: Cytogenetic and cancer aspects, in: Chromosomes and Cancer (J. German, ed.), pp. 619–636, John Wiley & Sons, New York.Google Scholar
  122. Hart, R. W., and Trosko, J. E., 1976, DNA repair processes in mammals, Interdiscip. Top. Gerontol. 9:134–167.Google Scholar
  123. Haslam, R. J., and Goldstein, S., 1974, Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro: Effects of prostaglandin E1 and of adrenaline, Biochem. J. 144:253–263.PubMedGoogle Scholar
  124. Hassell, T. M., Page, R. C., Narayanan, S., and Cooper, C. G., 1976, Diphenylhydantoin (Dilantin) gingival hyperplasia: Drug-induced abnormality of connective tissue, Proc. Natl. Acad. Sci. U.S.A. 73:2909–2912.PubMedGoogle Scholar
  125. Hayflick, L., 1965, The limited in vitro lifetime of human diploid cell strains, Exp. Cell Res. 37:614–636.PubMedGoogle Scholar
  126. Hecht, F., Koler, R. D., Rigas, D. A., Dahnke, G. S., Case, M. P., Tisdale, V., and Miller, R. W., 1966, Leukemia and lymphocytes in ataxia-telangiectasia, Lancet 2:1193.Google Scholar
  127. Hecht, F., McCaw, B. K., and Koler, R. D., 1973, Ataxia-telangiectasia-Clonal growth of translocation lymphocytes, N. Engl. J. Med. 289:286–291.PubMedGoogle Scholar
  128. Hernandez, A. L., DeLeon, B., Garcia de la Puenti, S., and Del Castillo, V., 1975, Ultrastructural renal lesions in the Cockayne syndrome: A case report, Rev. Invest. Clin. 27:153–158.PubMedGoogle Scholar
  129. Higurashi, M., and Conen, P. E., 1973, In vitro chromosomal radiosensitivity in chromosomal breakage syndromes, Cancer 32:380–383.PubMedGoogle Scholar
  130. Hoar, D. I., 1975, Phenotypic manifestations of ataxia-telangiectasia, Lancet 2:1048.PubMedGoogle Scholar
  131. Hoar, D. I., and Sargent, P., 1976, Chemical mutagen hypersensitivity in ataxia-telangiectasia, Nature (London) 261:590–592.Google Scholar
  132. Holliday, R., Porterfield, J. S., and Gibbs, D. D., 1974, Premature ageing and occurrence of altered enzyme in Werner’s syndrome fibroblasts, Nature (London) 248:762–763.Google Scholar
  133. Hopkins, D. J., and Horan, E. C., 1970, Glaucoma in the Hallermann-Streiff syndrome, Br. J. Ophthalmol. 54:416–422.PubMedGoogle Scholar
  134. Hoppe, W., and Koritsch, H. D., 1972, Another case of meningioma in a patient with Werner’s syndrome, Psychiatr. Neurol. Med. Psychol. 24:611–617.Google Scholar
  135. Howell, T. H., 1975, Old Age, p. 115, H. K. Lewis, London.Google Scholar
  136. Huang, K.-E., 1975, Pituitary response to synthetic luteinizing hormone-releasing hormone in patients with Turner’s syndrome, J. Clin. Endocrinol. Metab. 41:771–776.PubMedGoogle Scholar
  137. Huang, S.-W., and Maclaren, N. K., 1976, Insulin-dependent diabetes: A disease of autoaggression, Science 192:64–66.PubMedGoogle Scholar
  138. Hutchinson, D., 1971, Oral manifestations of oculomandibulodyscephaly with hypotrichosis (Hallermann-Streiff syndrome), Oral Surg. Oral Med. Oral Pathol. 31:234–244.PubMedGoogle Scholar
  139. Hutchinson, J., 1886, Congenital absence of hair and mammary glands, Trans. Med.-Chir. Soc. Edinburgh 69:473–477.Google Scholar
  140. 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.PubMedGoogle Scholar
  141. Ishii, T., and Hosoda, Y., 1974, Autopsy of Werner’s syndrome, Jpn. J. Geriatr. 11:408–415.Google Scholar
  142. Ishii, T., and Hosoda, Y., 1975, Werner’s syndrome: Autopsy report of one case, with a review of pathologic findings reported in the literature, J. Am. Geriatr. Soc. 23:145–154.PubMedGoogle Scholar
  143. Jervis, G. A., 1970, Premature senility in Down’s syndrome, Ann. N. Y. Acad. Sci. 171:559–561.Google Scholar
  144. Johansen, K. Soeldner, J. S., Gleason, R. E., Gottlieb, M. S., Park, B. N., Kaufmann, R. L., and Tan, M. H., 1975, Serum insulin and growth hormone response patterns in monozygotic twin siblings of patients with juvenile-onset diabetes, N. Engl. J. Med. 293:57–61.PubMedGoogle Scholar
  145. Jones, K. L., Smith, D. W., Harvey, M. A., Hall, B. D., and Quan, L., 1975, Older paterna age and fresh gene mutation: Data on additional disorders, J. Pediatr. 86:84–88.PubMedGoogle Scholar
  146. Kaiman, H., Lambie, R. W., and Metzl, 1969, Progeria: Case description, Clin. Pediatr. (Philadelphia) 8:411–415.Google Scholar
  147. Kato, H., and Stich, H. F., 1976, Sister chromatid exchanges in aging and repair-dehcient human fibroblasts, Nature (London) 260:447–448.Google Scholar
  148. Kaufman, M., Straisfeld, C., and Pinsky, L., 1977, Expression of androgen-responsive properties in human skin fibroblast strains of genital and nongenital origin, Somat. Cell Genet. 3:17–25.PubMedGoogle Scholar
  149. Keay, A. J., Oliver, M. F., and Boyd, G. S., 1955, Progeria and atherosclerosis, Arch. Dis. Child. 30:410–414.PubMedGoogle Scholar
  150. Kidd, R. L., and Wilgram, G. F., 1972, Morphea and progeria, Arch. Dermatol. 105:770–771.PubMedGoogle Scholar
  151. Kohn, R. R., 1975, Aging and cell division, Science 188:203–204.PubMedGoogle Scholar
  152. Korein, J., Steinman, P. A., and Senz, E. H., 1961, Ataxia-telangiectasia: Report of a case and review of the literature, Arch. Neurol. 4:272–280.PubMedGoogle Scholar
  153. Kraus, B. S., Gottlieb, M. A., and Meliton, H. R., 1970, The dentition in Rothmund’s syndrome, J. Am. Dent. Assoc. 81:895–915.PubMedGoogle Scholar
  154. Kristensen, J. K., 1975, Poikiloderma congénitale—An early case of Rothmund-Thomson’s syndrome, Ada Derm.-Venereol. 55:316–318.Google Scholar
  155. Kulenkamp, D., Scholz-Kordan, D., Passarge, E., Rudiger, H. W., and Ruprecht, K. W., 1973, Werner’s syndrome: A hereditable disorder of multiple organ systems, Andrologie 5:299–310.PubMedGoogle Scholar
  156. Kvale, P. A., Rutt, W. M., Birk, R. E., and Eyler, W. R., 1965, Werner’s syndrome, Henry Ford Hosp. Med. J. 13:411–420.PubMedGoogle Scholar
  157. Land, V. J., and Nogrady, M. B., 1969, Cockayne’s syndrome, J. Can. Assoc. Radiol. 20:194–203.PubMedGoogle Scholar
  158. Lanning, M., and Simil, A. S., 1970, Cockayne’s syndrome: Report of a case with normal intelligence, Z. Kinderheilkd. 109:70–75.PubMedGoogle Scholar
  159. Larregue, M., Cathelineau, G., Binet, O., Lhullier, N., Timsit, E., and Graciansky, P. De, 1974, Werner’s syndrome and hyperinsulinic diabetes, Ann. Dermatol. Syphiligr. 101:135–144.Google Scholar
  160. Latt, S. A., Stetten, G. M., Juergens, L. A., Buchanan, G. R., and Gerald, P. S., 1975, Induction by alklyating agents of sister chromatid exchanges and chromatid breaks in Fanconi’s anemia, Proc. Natl. Acad. Sci. U.S.A. 72:4066–4070.PubMedGoogle Scholar
  161. Leaf, A., 1973, Unusual longevity: The common denominator, Hosp. Pract. 8:79–86.Google Scholar
  162. Le Guilly, Y., Simon, M., Lenoir, P., and Bourel, M., 1973, Long-term culture of human adult liver cells: Morphological changes related to in vitro senescence and effect of donor’s age on growth potential, Gerontologia 19:303–313.PubMedGoogle Scholar
  163. Lelis, I. I., 1975, Progeria of adults (Werner’s syndrome) Ter. Arkh. 47(1):99–102.PubMedGoogle Scholar
  164. Lenz, W. D., and Majewski, F., 1974, A generalized disorder of the connective tissues with progeria, choanal atresia, symphalangism, hypoplasia of dentine and craniodiaphyseal hypostosis, Birth Defects: Orig. Artic. Ser. 10:133–136.Google Scholar
  165. Lestradet, H., Deschamps, I., and Giron, B., 1976, Insulin and free fatty acid levels during oral glucose tolerance tests and their relation to age in 70 healthy children, Diabetes 25:505–508.PubMedGoogle Scholar
  166. Levin, S., and Perlov, S., 1971, Ataxia-telangiectasia in Israel, with observations on its relationship to malignant disease, Isr. J. Med. Sci. 7:1535–1541.PubMedGoogle Scholar
  167. Levine, M. D., Alexander, E., and Rimoin, D. L., 1975, Progeroid syndrome, Birth Defects: Orig. Artie. Ser. 11:308–309.Google Scholar
  168. Lewis, M. B., 1972, Rothmund-Thomson syndrome and fibrocystic disease, Australas. J. Dermatol. 13:105–106.PubMedGoogle Scholar
  169. Lieberman, M. W., 1976, Approaches to the analysis of fidelity of DNA repair in mammalian cells, Int. Rev. Cytol. 45:1–23.PubMedGoogle Scholar
  170. Like, A. A., and Rossini, A. A., 1976, Streptozotocin-induced pancreatic insulitis: A new model of diabetes mellitus, Science 193:415–417.PubMedGoogle Scholar
  171. Lindeman, R. D., 1975, Age changes in renal function, in: The Physiology and Pathology of Human Aging (R. Goldman and M. Rockstein, eds.), pp. 19–38, Academic Press, New York.Google Scholar
  172. Lindsten, J., 1963, in: The Nature and Origin of X Chromosome Aberrations in Turner’s Syndrome (Almquist and Wiksell, eds.), Stockholm.Google Scholar
  173. Lindsten, J., Cerasi, E., Luft, R., and Hultquist, G., 1967, The occurrence of abnormal insulin and growth hormone (HGH) responses to sustained hyperglycaemia in a disease with sex chromosome aberrations (Turner’s syndrome): Including a histological study of the pancreas in two such patients, Acta Endocrinol.(Copenhagen) 56: 107–131.Google Scholar
  174. Linn, S., Kairis, M., and Holliday, R., 1976, Decreased fidelity of DNA polymerase activity isolated from aging human fibroblasts, Proc. Natl. Acad. Sci. U.S.A. 73:2818–2822.PubMedGoogle Scholar
  175. Lisker, R., and Cobo, A., 1970, Chromosome breakage in ataxia-telangiectasia, Lancet 1:618.PubMedGoogle Scholar
  176. Little, J. B., Epstein, J., and Williams, J. R., 1975, Repair of DNA strand breaks in progeric fibroblasts and aging human diploid cells, Basic Life Sci. 58:793–800.Google Scholar
  177. Lodi, A., Ravaglia, G., Grigioni, F., Ravaioli, R., and Gritti, F., 1974, Endocrine and morphological aspects of Werner’s syndrome, J. Clin. Med. 55:652–674.Google Scholar
  178. Louis-Bar, D., 1941, Sur un syndrome progressif comprenant des télangiectasies capillaires cutanées et conjonctivales, à disposition naevoïde et des troubles cérébelleux, Confin. Neurol. 4:32–42.Google Scholar
  179. MacDonald, W. B., Fitch, K. D., and Lewis, I. C., 1960, Cockayne’s syndrome: A heredo-familial disorder of growth and development, Pediatrics 25:997–1007.PubMedGoogle Scholar
  180. Macleod, W., 1966, Progeria, Br. J. Radiol. 39:224–226.PubMedGoogle Scholar
  181. MacNamara, B. G., Farn, K. T., Mitra, A. K., Lloyd, J. K., and Fosbrooke, A. S., 1970, Progeria: Case report with long-term studies of serum lipids, Arch. Dis. Child. 45:553–560.PubMedGoogle Scholar
  182. Malamud, N., 1972, Neuropathology of organic brain syndromes associated with aging, in: Aging and the Brain (CM. Gaitz, ed.), pp. 63–87, Plenum Press, New York.Google Scholar
  183. Marble, A., and Ramos, E., 1971, Cancer and diabetes, in: Joslin’s Diabetes Mellitus (A. Marble, P. White, R. F. Bradley, and L. P. Krall, eds.), pp. 695–700, Lea & Febiger, Philadelphia.Google Scholar
  184. Marcondes, E., Campos, J. V., Barbieri, D., Quarentei, G., and Cavallo, A., 1969, Progeria: Case report with progressive systemic sclerotic manifestations since birth, Rev. Hosp. Clin. Fac. Med. Univ. Sao Paulo 24:147–154.Google Scholar
  185. Margolin, F. R., and Steinbach, H. L., 1968, Progeria: Hutchinson-Gilford syndrome, Am. J. Roentgenol. Radium Ther. Nucl. Med. 103:173–178.PubMedGoogle Scholar
  186. Marks, H. H., and Krall, L. P., 1971, Onset, course, prognosis and mortality in diabetes mellitus, in: Joslin’s Diabetes Mellitus (A. Marble, P. White, R. F. Bradley, and L. P. Krall, eds.), pp. 209–254, Lea & Febiger, Philadelphia.Google Scholar
  187. Martin, G. M., 1977, Genetic syndromes in man with potential relevance to the pathobiology of aging, in: Genetic Effects on Aging, Birth Defects: Orig. Artic. Ser. (D. Bergsma and D. E. Harrison, eds.) The National Foundation-March of Dimes, New York (in press).Google Scholar
  188. Martin, G. M., Sprague, CA., and Epstein, C.J., 1970, Replicative life-span of cultivated human cells: Effects of donor’s age, tissue, and genotype, Lab. Invest. 23:86–92.PubMedGoogle Scholar
  189. Martin, G. M., Sprague, C. A., Norwood, T. H., and Pendergrass, W. R., 1974, Clonal selection, attenuation and differentiation in an in vitro model of hyperplasia, Am. J. Pathol. 74:137–154.PubMedGoogle Scholar
  190. Martin, J. J., Deberot, R., Philippart, M., Van Acker, K. J., and Hooft, C., 1971, Peculiar dysmorphic syndrome with orthochromatic leucodystrophy: Discussion of its relationship with Cockayne’s syndrome and Pelizaeus-Merzbacher’s disease, Acta Neuropathol. 18:224–233.PubMedGoogle Scholar
  191. Maurer, R. M., and Langford, O. L., 1967, Rothmund’s syndrome: A cause of résorption of phalangeal tufts and dystrophic calcification, Radiology 89:706–708.PubMedGoogle Scholar
  192. McCaw, B. K., Hecht, F., Harnden, D. G., and Teplitz, R. L., 1975, Somatic rearrangement of chromosome 14 in human lymphocytes, Proc. Natl. Acad. Sci. U.S.A. 72:2071–2075.PubMedGoogle Scholar
  193. McFarlin, D. W., Strober, W., and Waldmann, T. A., 1972, Ataxia telangiectasia, Medicine (Baltimore) 51:281–314.Google Scholar
  194. McKusick, V. A., 1963, Medical genetics, 1962, J. Chronic Dis. 16:457–634.PubMedGoogle Scholar
  195. McKusick, V. A., 1975, Mendelian Inheritance in Man—Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes, Johns Hopkins University Press, Baltimore.Google Scholar
  196. McKusick, V. A., and Cross, H. E., 1966, Ataxia-telangiectasia and Swiss-type agammaglobulinemia: Two genetic disorders of the immune mechanism in related Amish sibships, J. Am. Med. Assoc. 195:739–745.Google Scholar
  197. Meissner, W. A., and Legg, M. A., 1971, The pathology of diabetes, in: Joslin’s Diabetes Mellitus (A. Marble, P. White, R. F. Bradley, and L. P. Krall, eds.), pp. 157–190, Lea & Febiger, Philadelphia.Google Scholar
  198. Menkes, J. H., and Stein, N., 1973, Fibroblast cultures in Huntington’s disease, N. Engl. J. Med. 288:856–857.PubMedGoogle Scholar
  199. Miller, M. E., and Chatten, J., 1967, Ovarian changes in ataxia telangiectasia, Acta Paediatr. Scand. 56:559–561.PubMedGoogle Scholar
  200. Miller, R. W., 1970, Neoplasia and Down’s syndrome, Ann. N. Y. Acad. Sci. 171:637–644.Google Scholar
  201. Moosa, A., and Dubowitz, V., 1970, Peripheral neuropathy in Cockayne’s syndrome, Arch. Dis. Child. 45:674–677.PubMedGoogle Scholar
  202. Moossey, J., 1967, The neuropathology of Cockayne’s syndrome, J. Neuropathol. Exp. Neurol. 26:654–660.Google Scholar
  203. Morgan, J. L., Holcomb, T. M., and Morrissey, R. W., 1968, Radiation reaction in ataxia telangiectasia, Am. J. Dis. Child. 116:577–558.Google Scholar
  204. Morse, L. S., and Pauling, C., 1975, Induction of error-prone repair as a consequence of DNA ligase deficiency in E. coli, Proc. Natl. Acad. Sci. U.S.A. 72:4645–4649.Google Scholar
  205. Mostafa, A. H., and Gabr, M., 1954, Heredity in progeria: With follow-up of two affected sisters, Arch. Pediatr. 71:163–172.PubMedGoogle Scholar
  206. Muller, J., Kunkov, A. A., and Kepertov, A. A., 1969, Werner’s syndrome: Case report, Wien. Z. Inn. Med. Ihre Grenzgeb. 50:112–116.Google Scholar
  207. Murphy, R., and Achkar, E. J., 1966, Werner’s syndrome, Lahey Clin. Found. Bull. 15: 1–7.PubMedGoogle Scholar
  208. Neill, C. A., and Dingwall, M. M., 1950, A syndrome resembling progeria: A review of two cases, Arch. Dis. Child. 25: 213–223.PubMedGoogle Scholar
  209. Nelson, P. G., Pyke, D. A., Cudworth, A. G., Woodrow, J. C., and Batchelor, J. R., 1975, Histocompatibility antigens in diabetic identical twins, Lancet 2:193–194.PubMedGoogle Scholar
  210. Neufeld, E. F., Lim, T. W., and Shapiro, L. J., 1975, Inherited disorders of lysosomal metabolism, Annu. Rev. Biochem. 44:357–376.PubMedGoogle Scholar
  211. Nielsen, J., Johansen, K., and Yde, H., 1969, The frequency of diabetes mellitus in patients with Turner’s syndrome and pure gonadal dysgenesis, Acta Endocrinol. (Copenhagen) 62:251–269.Google Scholar
  212. Nienhaus, A. J., De Jong, B., and Kate, L. P. Ten, 1971, Fibroblast culture in Werner’s syndrome, Humangenetik 13:244–246.PubMedGoogle Scholar
  213. Nissim, J. E., 1971, Rothmund syndrome, Birth Defects: Orig. Artie. Ser. 7:294–295.Google Scholar
  214. Norman, R. M., and Tingey, A. H., 1966, Syndrome of micrencephaly, strio-cerebellar calcifications and leucodystrophy, J. Neurol. Neurosurg. Psychiatry 29:157–163.Google Scholar
  215. Nowell, P. C., 1976, The clonal evolution of tumor cell populations: Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression, Science 194:23–28.PubMedGoogle Scholar
  216. Oates, R. K., Lewis, M. B., and Walker-Smith, J. A., 1971, The Rothmund-Thomson syndrome: Case report of an unusual syndrome, Aust. Paediatr. J. 7:103–107.PubMedGoogle Scholar
  217. Ohno, T., and Hiroaka, M., 1966, Renal lesions in Cockayne’s syndrome, Tohoku J. Exp. Med. 89:151–166.PubMedGoogle Scholar
  218. Orgel, L. E., 1973, Ageing of clones of mammalian cells, Nature (London) 243: 441–445.Google Scholar
  219. Oxford, J. M., Harnden, D. G., Parrington, J. M., and Delhanty, J. D., 1975, Specific chromosome aberrations in ataxia telangiectasia, J. Med. Genet. 12:251–262.PubMedGoogle Scholar
  220. Ozonoff, M. B., and Clemett, A. R., 1967, Progressive osteolysis in progeria, Am. J. Roentgenol. Radium Ther. Nucl. Med. 100:75–79.PubMedGoogle Scholar
  221. Paddison, R. M., Moossy, J., Derbes, V. J., and Kloepfer, H. W., 1963, Cockayne’s syndrome: A report of five new cases with biochemical, chromosomal, dermatologie, genetic and neuropathologic observations, Dermatol. Trop. Ecol. Geogr. 2:195–203.Google Scholar
  222. Palmer, G., 1966, Rothmund-Thomson syndrome, Australas. J. Dermatol. 8:253–254.Google Scholar
  223. Palumbo, P. J., Elveback, L. R., Chu, C.-P., Connolly, D. C., and Kurland, L. T., 1976, Diabetes mellitus: Incidence, prevalence, survivorship, and causes of death in Rochester, Minnesota, 1945-1970, Diabetes 25:566–573.PubMedGoogle Scholar
  224. Paterson, D., 1922, Case of progeria, Proc. R. Soc. Med. 16:42.Google Scholar
  225. Paterson, M. C., Smith, B. P., Lohman, P. H. M., Anderson, A. K., and Fishman, L., 1976, Defective excision repair of ϒ-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts, Nature (London) 260:444–447.Google Scholar
  226. Payer, G., 1969, Two cases of Werner’s syndrome, Klin. Monatsbl. Augenheilkd. 155:901–904.PubMedGoogle Scholar
  227. Penrose, L. S., and Smith, G. F., 1966, Down’s Anomaly, Churchill, London.Google Scholar
  228. Perlman, H. H., Luscombe, H. A., and Rosenberg, P. E., 1967, Poikiloderma congénitale of Thomson-Rothmund vs. localized linear scleroderma, Arch. Dermatol. 96:593–594.PubMedGoogle Scholar
  229. Perry, R. P., 1976, Processing of RNA, Annu. Rev. Biochem. 45:605–630.PubMedGoogle Scholar
  230. Peterson, R. D. A., Kelly, W. D., and Good, R. A., 1964, Ataxia-telangiectasia: Its association with a defective thymus, immunological-deficiency disease and malignancy, Lancet 1:1189–1193.PubMedGoogle Scholar
  231. Peterson, R. D. A., Cooper, M. D., and Good, R. A., 1966, Lymphoid tissue abnormalities associated with ataxia-telangiectasia, Am. J. Med. 41:342–359.PubMedGoogle Scholar
  232. Pfeiffer, R. A., and Backmann, K. D., 1973, An atypical case of Cockayne’s syndrome, Clin. Genet. 4:28–32.PubMedGoogle Scholar
  233. Piazzini, M., Conti, C., Guazzelli, R., and Bigozzi, U., 1976, On a rare case of progeria in brother and sister, Acta Med. Auxol. 8:75–79.Google Scholar
  234. Poon, P. K., O’Brien, R. L., and Parker, J. W., 1974, Defective DNA repair in Fanconi’s anaemia, Nature (London) 250:223–225.Google Scholar
  235. Predescu, V., Christodorescu, D., Coltoiu, A., Costiner, E., Hagiopol, V., and Alexianu, M., 1973, Cockayne’s syndrome, Arch. Fr. Pediatr. 30:527–532.PubMedGoogle Scholar
  236. Rainbow, A. J., and Howes, M., 1977, Decreased repair of gamma ray damaged DNA in progeria, Biochem. Biophys. Res. Commun. 77:714–719.Google Scholar
  237. Rary, J. M., Bender, M. A., and Kelly, T. E., 1975, A 14/14 marker chromosome lymphocyte clone in ataxia telangiectasia, J. Hered. 66:33–35.PubMedGoogle Scholar
  238. Rasio, E., Antaki, A., and Van Campenhout, J., 1976, Diabetes mellitus in gonadal dysgenesis: Studies of insulin and growth hormone secretion, Eur. J. Clin. Invest. 6:59–66.PubMedGoogle Scholar
  239. Rava, G., 1967, Su un nucleo familiare di progeria, Minerva Med. 58:1502–1509.PubMedGoogle Scholar
  240. Regan, J. D., and Setlow, R. B., 1974, DNA repair in human progeroid cells, Biochem. Biophys. Res. Common. 59:858–864.Google Scholar
  241. Reichel, W., and Garcia-Bunuel, R., 1970, Pathologic findings in progeria: Myocardial fibrosis and lipofuscin pigment, Am. J. Clin. Pathol. 53:243–253.PubMedGoogle Scholar
  242. Reichel, W., Garcia-Bunuel, R., and Dilallo, J., 1971a, Progeria and Werner’s syndrome as models for the study of normal human aging, J. Am. Geriatr. Soc. 19: 369–375.PubMedGoogle Scholar
  243. Reichel, W., Bailey, J. A., Zigel, S., Garcia-Bunuel, R., and Knox, G., 1971b, Radiological findings in progeria, J. Am. Geriatr. Soc. 19:657–674.PubMedGoogle Scholar
  244. Reiss, U., and Gershon, D., 1976, Rat liver Superoxide dismutase: Purification and age-related modifications, Eur. J. Biochem. 63:617–623.PubMedGoogle Scholar
  245. Remsen, J. F., and Cerutti, P. A., 1976, Deficiency of gamma-ray excision repair in skin fibroblasts from Fanconi’s anemia, Proc. Natl. Acad. Sci. U.S.A. 73:2419–2423.PubMedGoogle Scholar
  246. Renold, A. E., Stauffacher, W., and Cahill, G. F. Jr., 1972, Diabetes mellitus, in: The Metabolic Bases of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), pp. 83–118, McGraw-Hill, New York.Google Scholar
  247. Reye, C., and Mosman, N. S. W., 1960, Ataxia-telangiectasia, Am. J. Dis. Child. 99:238–247.Google Scholar
  248. Reynolds, C., O’Duffy, J. D., and Sams, W., 1972, Werner’s syndrome: Case report of a variant, Minn. Med. 55:917–921.PubMedGoogle Scholar
  249. Rheinwald, J. G., and Green, H., 1975, Serial cultivation of strains of human epidermal keratinocytes: The formation of keratinizing colonies from single cells, Cell 6:331–337.PubMedGoogle Scholar
  250. Richards, D., 1974, Werner’s syndrome, Proc. R. Soc. Med. 67:721–722.Google Scholar
  251. Riggs, W., and Seibert, J., 1972, Cockayne’s syndrome: Roentgen findings, Am. J. Roentgenol. Radium Ther. Nucl. Med. 116:623–633.PubMedGoogle Scholar
  252. Rosen, R. S., Cimini, R., and Coblentz, D., 1970, Werner’s syndrome, Br. J. Radiol. 43:193–198.PubMedGoogle Scholar
  253. Rosenbloom, A. L., and Debusk, F. L., 1971, Progeria of Hutchinson-Gilford: A caricature of aging, Am. Heart J. 83:287–289.Google Scholar
  254. Rosenbloom, A. L., Karacan, I. J., and DeBusk, F. L., 1970, Sleep characteristics and endocrine response in progeria, J. Pediatr. 77:692–695.PubMedGoogle Scholar
  255. Rosenbloom, A. L., Wheeler, L., Bianchi, R., Chin, F. T., Tiwary, C. M., and Grgic, A., 1975, Age-adjusted analysis of insulin responses during normal and abnormal glucose tolerance tests in children and adolescents, Diabetes 24:820–828.PubMedGoogle Scholar
  256. Rosenbloom, A. L., Goldstein, S., and Yip, C. C., 1976, Insulin binding to cultured human fibroblasts increases with normal and precocious aging, Science 193:412–415.PubMedGoogle Scholar
  257. Rothmund, A., 1868, Über Kataracten in Verbindung mit einer eigenthen Haut Degeneration, Graefe. Arch. Ophthalmol. 14:159–182.Google Scholar
  258. Rothstein, M., 1977, Recent developments in the age-related alteration of enzymes: A review, Mech. Ageing Dev. 6:241–257.PubMedGoogle Scholar
  259. Rowe, J. W., Andres, R., Tobin, J. D., Norrs, A. H., and Shock, N. W., 1976, The effect of age on creatinine clearance in man: A cross-sectional and longitudinal study, J. Gerontol. 31:155–163.PubMedGoogle Scholar
  260. Rowlatt, U., 1969, Cockayne’s syndrome: Report of case with necropsy findings, Acta Neuropathol. 14:52–61.PubMedGoogle Scholar
  261. Roy, S., Srivastava, R. N., Gupta, P. C., and Mayekar, G., 1973, Ultrastructure of peripheral nerve in Cockayne’s syndrome, Acta Neuropathol. 24:345–349.PubMedGoogle Scholar
  262. Roychoudhury, D. S., and Banerjee, A. K., 1968, Heredofamilial study of Weber-Cockayne disease, Bull. Calcutta Sch. Trop. Med. 16:12–13.PubMedGoogle Scholar
  263. Rubin, P., and Casarett, G. W., 1968, Clinical Radiation Pathology, pp. 881–893, W. B. Saunders Co., Philadelphia.Google Scholar
  264. Ruddle, F. H., and Creagan, R. P., 1975, Parasexual approaches to the genetics of man, Annu. Rev. Genet. 9:407–486.PubMedGoogle Scholar
  265. Ryan, J. M., and Cristofalo, V. J., 1975, Chromatin template activity during aging in vitro, Exp. Cell Res. 90:456–458.PubMedGoogle Scholar
  266. Saunders, J. W., and Fallon, J. F., 1966, Cell death in morphogenesis, in: Major Problems in Developmental Biology (M. Locke, ed.), pp. 289–314, Academic Press, New York.Google Scholar
  267. Schalch, D. S., McFarlin, D., and Barlow, M. H., 1970, An unusual form of diabetes mellitus in ataxia telangiectasia, N. Engl. J. Med. 282:1396–1402.PubMedGoogle Scholar
  268. Schmickel, R. D., Chu, E. H. Y., and Trosko, J., 1975, The definition of a cellular defect in two patients with Cockayne syndrome, Pediatr. Res. 9: 317 (abstract).Google Scholar
  269. Schneider, E. L., and Chase, G. A., 1976, Relationship between age of donor and in vitro life span of human diploid fibroblasts, Interdiscip. Top. Gerontol. 10:62–69.Google Scholar
  270. Schneider, E. L., and Epstein, C. J., 1972, Replication rate and lifespan of cultured fibroblasts in Down’s syndrome, Proc. Soc. Exp. Biol. Med. 141:1092–1096.PubMedGoogle Scholar
  271. Schneider, E. L., and Mitsui, Y., 1976, The relationship between in vitro cellular aging and in vivo human age, Proc. Natl. Acad. Sci. U.S.A. 73:3584–3588.PubMedGoogle Scholar
  272. Schneider, E. L., and Shorr, S. S., 1975, Alteration in cellular RNA’s during the in vitro lifespan of cultured human diploid fibroblasts, Cell 6:179–184.PubMedGoogle Scholar
  273. Schumacher, K., Rodermund, O. E., and Doepfmer, R., 1969, Werner’s syndrome: Contribution to symptomatology and etiology, Arch. Klin. Med. 216:116–147.PubMedGoogle Scholar
  274. Segal, D. J., and McCoy, E. E., 1974, Studies on Down’s syndrome in tissue culture. I. Growth rates and protein contents of fibroblast cultures, J. Cell. Physiol. 83:85–90.PubMedGoogle Scholar
  275. Sexton, G. B., 1954, Thomson’s syndrome (poikiloderma congénitale), Can. Med. Assoc. J. 70:662–665.PubMedGoogle Scholar
  276. Shuster, J., Hart, Z., Stimson, C. W., Brough, A. J., and Poulik, M. D., 1966, Ataxiatelangiectasia with cerebellar tumor, Pediatrics 37:776–786.PubMedGoogle Scholar
  277. Siemens, H. W., 1963, The lens, in: Genetics and Ophthalmology (P. J. Waardenburg, A. Franceschetti, and D. Klein, eds.), p. 896, Charles C. Thomas, Springfield, Illinois. Silver, H. K., 1966, Rothmund-Thomson syndrome: An oculocutaneous disorder, Am. J. Dis. Child. 111:182–190.Google Scholar
  278. Simig, I., and Fizelov, A. E., 1976, Werner’s syndrome, Cesk. Oftalmol. 32:45–49.PubMedGoogle Scholar
  279. Singal, D. P., and Blajchman, M. A., 1973, Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus, Diabetes 22:429–432.PubMedGoogle Scholar
  280. Singal, D. P., and Goldstein, S., 1973, Absence of detectable HL-A antigens on cultured fibroblasts in progeria, J. Clin. Invest. 52:2259–2263.PubMedGoogle Scholar
  281. Smith, D. W., 1976, Ataxia-telangiectasia syndrome in: Recognizable Patterns of Human Malformation, pp. 102–103, W. B. Saunders Co., Philadelphia.Google Scholar
  282. Smith, G. F., and Berg, J. M., 1976, Down’s Anomaly, pp. 239–246, Churchill Livingstone, Edinburgh.Google Scholar
  283. Sourander, P., Bonnevier, J. O., and Olsson, Y., 1966, A case of ataxia telangiectasia with lesions in the spinal cord, Acta Neurol. Scand. 42:354–366.PubMedGoogle Scholar
  284. Spark, H., 1965, Cachetic dwarfism resembling the Cockayne-Neill type, J. Pediatr. 66:41–47.PubMedGoogle Scholar
  285. Spence, A. M., and Herman, M. M., 1973, Critical re-examination of the premature aging concept in progeria: A light and electron microscopic study, Mech. Ageing Dev. 2:211–227.PubMedGoogle Scholar
  286. Sri-Skanda-Rajah-Sivayoham, I., and Ratnaike, V. T., 1975, Rothmund-Thomson syndrome in an Oriental patient, Ann. Ophthalmol. 7:417–420.PubMedGoogle Scholar
  287. Srivastava, R. N., Gupta, P. C., Mayekar, G., and Roy, S., 1974, Cockayne’s syndrome in two sisters, Acta Paediatr. Scand. 63:461–464.PubMedGoogle Scholar
  288. Stearns, E. L., MacDonnell, J. A., Kaufman, B. J., Padua, R., Lucman, T. S., Winter, J. S. D., and Faiman, C., 1974, Declining testicular function with age, Am. J. Med. 57:761–766.PubMedGoogle Scholar
  289. Steele, R. W., and Bass, J. W., 1970, Hallermann-Streiff syndrome: Clinical and prognostic considerations, Am. J. Dis. Child. 120:462–465.PubMedGoogle Scholar
  290. Stein, G. S., and Stein, J. L., 1976, In vitro studies of transcription as a function of age in mammalian cells, Interdiscip. Top. Gerontol. 10:83–99.Google Scholar
  291. Strober, W., Wochner, R. D., Barlow, M. H., McFarlin, D. E., and Waldmann, T. A., 1968, Immunoglobulin metabolism in ataxia telangiectasia, J. Clin. Invest. 47:1905–1915.PubMedGoogle Scholar
  292. Tadjoedin, M. K., and Fraser, F. C., 1965, Heredity of ataxia telangiectasia (Louis-Bar syndrome), Am. J. Dis. Child. 110:64–68.PubMedGoogle Scholar
  293. Talbot, N. B., Butler, A. M., Pratt, E. L., MacLachlan, E. A., and Tannheimer, J., 1945, Progeria: Clinical, metabolic and pathologic studies on a patient, Am. J. Dis. Child. 69:267–279.Google Scholar
  294. Tanenbaum, M. H., 1965, Werner’s syndrome: Progeria of the adult, Arch. Intern. Med. 116:499–504.PubMedGoogle Scholar
  295. Tao, L. C., Stecker, E., and Gardner, H. A., 1971, Werner’s syndrome and acute myeloid leukemia, Can. Med. Assoc. J. 105:951–953.PubMedGoogle Scholar
  296. Tattersall, R. B., and Fajans, S. S., 1975, A difference between the inheritance of classical juvenile-onset and maturity-onset type of diabetes of young people, Diabetes 24:44–53.PubMedGoogle Scholar
  297. Taylor, A. M. R., Harnden, D. G., Arlett, C. F., Harcourt, S. A., Lehmann, A. R., Stevens, S., and Bridges, B. A., 1975, Ataxia telangiectasia: A human mutation with abnormal radiation sensitivity, Nature (London) 258:427–429.Google Scholar
  298. Taylor, W. B., 1957, Rothmund’s syndrome—Thomson’s syndrome, Arch. Dermatol. 75:236–244.Google Scholar
  299. Taymor, M. L., Toshihiro, A., and Pheteplace, C., 1968, Serum levels of FSH and LH by radioimmunoassay, in: Gonadotropins 1968, Proceedings of the Workshop Conference—Vista Hermosa, More., Mexico (Rosemberg, ed.), pp. 349–365, Geron-X, California.Google Scholar
  300. Thannhauser, S. J., 1945, Werner’s syndrome (progeria of the adult) and Rothmund’s syndrome: Two types of closely related heredofamilial atrophic dermatosis with juvenile cataracts and endocrine features: A critical study with five new cases, Ann. Intern. Med. 23:559.Google Scholar
  301. Thomsen, M., Platz, P., Ortved Andersen, O., Christy, M., Lyngsoe, J., Nerup, J., Rasmussen, K., Ryder, L. P., Staub Nelsen, L., and Svejgaard, A., 1975, MLC typing in juvenile diabetes mellitus and idiopathic Addison’s disease, Transplant. Rev. 22:125–147.PubMedGoogle Scholar
  302. Thomson, M. S., 1936, Poikiloderma congénitale, Br. J. Dermatol. 48: 221–234.Google Scholar
  303. Tibbetts, P. G., Rose, H. D., and Kersting, D. W., 1968, Werner’s syndrome, Wis. Med. J. 67: 550–557.PubMedGoogle Scholar
  304. Tokunaga, M., Futami, T., Wakamatsu, E., Endo, M., and Yosizawa, Z., 1975, Werner’s syndrome as “hyaluronuria,” Clin. Chim. Acta 62:89–96.PubMedGoogle Scholar
  305. Turner, H. H., 1938, A syndrome of infantilism, congenital webbed neck and cubitus valgus, Endocrinology 23:566–574.Google Scholar
  306. Ufermann, K., Heege-Dohr, R., and Kosenow, W., 1973, Ocular manifestation in Cockayne’s syndrome, Klin. Monatsbl. Augenheilkd. 162:655–658.PubMedGoogle Scholar
  307. Ungar, B., Stocks, A. E., Martin, F. I. R., Whittingham, S., and Mackay, I. R., 1968, Intrinsic factor antibody, parietal-cell antibody, and latent pernicious anemia in diabetes mellitus, Lancet 2:415–418.PubMedGoogle Scholar
  308. Unger, R. H., 1976, Diabetes and the alpha cell, Diabetes 25:136–151.PubMedGoogle Scholar
  309. Valdiserri, L., and Stricchiola, G., 1974, Hutchinson-Gilford progeria in a 14-year-old adolescent, Chir. Organi Mov. 61:291–300.PubMedGoogle Scholar
  310. Van Campenhout, J., Antaki, A., and Rasio, E., 1973, Diabetes mellitus and thyroid autoimmunity in gonadal dysgenesis, Fertil. Steril. 24:1–9.PubMedGoogle Scholar
  311. Vandaele, R., 1973, Werner’s syndrome: Familial ulcerous scleroderma with cataract and diabetes, Arch. Belg. Dermatol. Syphiligr. 29:251–254.PubMedGoogle Scholar
  312. Viegas, J., Souza, P. L., and Salzano, F. M., 1974, Progeria in twins, J. Med. Genet. 11:384–386.PubMedGoogle Scholar
  313. Villee, D. B., Nichols, G., Jr., and Talbot, N. B., 1969, Metabolic studies in two boys with classical progeria, Pediatrics 43: 207–216.PubMedGoogle Scholar
  314. Vincent, R. A., Sheridan, R. B., and Huang, P. C., 1975, DNA strand breakage repair in ataxia telangiectasia fibroblast-like cells, Mutat. Res. 33:357–366.PubMedGoogle Scholar
  315. Vracko, R., and Benditt, E. P., 1974, Manifestations of diabetes mellitus: Their possible relationships to an underlying cell defect, Am. J. Pathol. 75:204–223.PubMedGoogle Scholar
  316. Vracko, R., and Benditt, E. P., 1975, Restricted replicative life-span of diabetic fibroblasts in vitro: Its relation to microangiopathy, Fed. Proc. Fed. Am. Soc. Exp. Biol. 34:68–70.Google Scholar
  317. Wahl, J. W., and Ellis, P. P., 1965, Rothmund-Thomson syndrome, Am. J. Ophthalmol. 60: 722–726.PubMedGoogle Scholar
  318. Walburg, H. E., 1975, Radiation-induced life shortening and premature aging, Adv. Radiat. Biol. 5:145–179.Google Scholar
  319. Waldmann, T. A., and McIntire, K. R., 1972, Serum-alpha-fetoprotein levels in patients with ataxia-telangiectasia, Lancet 2:1112–1115.PubMedGoogle Scholar
  320. Wells, R. S., 1972, Werner’s syndrome: Acrogeria, Proc. R. Soc. Med. 65:525–526.PubMedGoogle Scholar
  321. Welsh, O., 1975, Study of a family with a new progeroid syndrome, Birth Defects: Orig. Artie. Ser. 11:25–38.Google Scholar
  322. Werder, E. A., Murset, G., Illig, R., and Prader, A., 1975, Hypogonadism and parathyroid adenoma in congenital poikiloderma (Rothmund-Thomson syndrome), Clin. Endocrinol. (Oxford) 4: 75–82.Google Scholar
  323. Werner, O., 1904, Über Katarakt in Verbindung mit Sklerodermie (doctoral dissertation, Kiel University), Schmidt and Klaunig, Kiel, Germany.Google Scholar
  324. Wertelecki, W., Fraumeni, J. F., and Mulvihill, J. J., 1970, Non-gonadal neoplasia in Turner’s syndrome, Cancer 26:485–488.PubMedGoogle Scholar
  325. Wicks, A. C., and Wall, D. W., 1974, Werner’s syndrome: A case report in a Rhodesian African, Cent. Afr. J. Med. 20:251–254.PubMedGoogle Scholar
  326. Wiedemann, H. R., 1969, Some progeroid cases and their diagnostic classification, Z. Kinderheilkd. 107:91–106.PubMedGoogle Scholar
  327. Yasuhara, M., Kiyokane, K., Sakai, T., Oiwa, T., and Hashi, N., 1974, A case of Werner’s syndrome, Jpn. J. Hum. Genet. 19:86–87.Google Scholar
  328. Zacharski, L. R., and McIntyre, O. R., 1973, Tissue factor (thromboplastin, Factor III) synthesis by cultured cells, J. Med. 4:118–131.Google Scholar
  329. Zackai, A. H., Weber, D., and Noth, R., 1974, Cardiac findings in Werner’s syndrome, Geriatrics 29:141–148.PubMedGoogle Scholar
  330. Zamith, V. A., Campos, J. V., and Chizzotti, M. T., 1974, Rothmund’s syndrome: Serum and urine aminogram—Study of a family, Rev. Bras. Pesqui. Med. Biol. 7:23–27.PubMedGoogle Scholar
  331. Zeldis, S. M., Nemerson, Y., Pitlick, F. A., and Lentz, T. L., 1972, Tissue factor (thromboplastin): Localization to plasma membranes by peroxidase-conjugated antibodies, Science 175: 766–768.PubMedGoogle Scholar
  332. Zonana, J., and Rimoin, D. L., 1976, Current concepts in genetics: Inheritance of diabetes mellitus, N. Engl. J. Med. 295:603–605.PubMedGoogle Scholar
  333. Zucker-Franklin, D., Rifkin, H., and Jacobson, H. G., 1968, Werner’s syndrome: An analysis of ten cases, Geriatrics 23:123–135.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • Samuel Goldstein
    • 1
  1. 1.Departments of Medicine and BiochemistryMcMaster UniversityHamiltonCanada

Personalised recommendations