Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence

PLoS One

Shozo Yamada¹  Kenichi Yoshida²  Yutaka Takahashi²  Kentaro Suda²  Wataru Ogawa²  Yukiko Odake²  Michiko Takahashi²  Ryusaku Matsumoto²  Hironori Bando²  Hitoshi Nishizawa²  Genzo Iguchi³  Hidenori Fukuoka³ 

[1] Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Minato-ku, Tokyo, Japan;Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan;Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Hyogo, Japan

关键词: Telomeres;    Telomere length;    Acromegaly;    Fibroblasts;    Diabetes mellitus;    Death rates;    Senescence;    Hypertension;   

DOI  :  10.1371/journal.pone.0140189

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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. Conclusion 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.

【 授权许可】

CC BY