title: Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.
abstract: OBJECTIVE
  Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases.
  
  
  METHODS
  We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts.
  
  
  RESULTS
  Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence.
  
  
  CONCLUSIONS
  Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Matsumoto
authors.affiliation: Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Hyogo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Fukuoka
authors.affiliation: Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Hyogo, Japan.
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Odake
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Bando
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suda
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Minato-ku, Tokyo, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000172:Acromegaly / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016922:Cellular Senescence; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D059506:Telomere Shortening
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I