Reductions in serum IGF‐1 during aging impair health span

Aging Cell

Zhenwei Gong⁷  Oran Kennedy²  Hui Sun³  YingJie Wu³  Garry A Williams³  Laura Klein⁷  Luis Cardoso⁶  Ronald W. Matheny Jr⁴  Gene B. Hubbard⁵  Yuji Ikeno⁵  Roger P. Farrar¹  Mitchell B Schaffler⁶  Martin L Adamo⁴  Radhika H Muzumdar⁷ 

[1]Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, USA

[2]Department of Orthopaedic Surgery, New York University, Hospital for Joint Diseases,  NY, NY, USA

[3]David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA

[4]Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX, USA

[5]Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA

[6]Department of Biomedical Engineering, The City College of New York, New York, NY, USA

[7]Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA

关键词: aging;    bone;    growth hormone;    IGF;    insulin‐sensitivity;    LID;    lifespan;    liver;    tumor;   

DOI  :  10.1111/acel.12188

来源: Wiley

【 摘 要 】

Summary

In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF-1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/IGF-1 axis are unable to clearly distinguish between developmental and age-related effects of GH/IGF-1 on health. To overcome this caveat, we developed an inducible liver IGF-1-deficient (iLID) mouse that allows temporal control of serum IGF-1. Deletion of liver Igf -1 gene at one year of age reduced serum IGF-1 by 70% and dramatically impaired health span of the iLID mice. Reductions in serum IGF-1 were coupled with increased GH levels and increased basal STAT5B phosphorylation in livers of iLID mice. These changes were associated with increased liver weight, increased liver inflammation, increased oxidative stress in liver and muscle, and increased incidence of hepatic tumors. Lastly, despite elevations in serum GH, low levels of serum IGF-1 from 1 year of age compromised skeletal integrity and accelerated bone loss. We conclude that an intact GH/IGF-1 axis is essential to maintain health span and that elevated GH, even late in life, associates with increased pathology.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.