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Differential effects of IGF-1 deficiency during the life span on structural and biomechanical properties in the tibia of aged mice

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Abstract

Advanced aging is associated with the loss of structural and biomechanical properties in bones, which increases the risk for bone fracture. Aging is also associated with reductions in circulating levels of the anabolic signaling hormone, insulin-like growth factor (IGF)-1. While the role of IGF-1 in bone development has been well characterized, the impact of the age-related loss of IGF-1 on bone aging remains controversial. Here, we describe the effects of reducing IGF-1 at multiple time points in the mouse life span—early in postnatal development, early adulthood, or late adulthood on tibia bone aging in both male and female igf f/f mice. Bone structure was analyzed at 27 months of age using microCT. We find that age-related reductions in cortical bone fraction, cortical thickness, and tissue mineral density were more pronounced when IGF-1 was reduced early in life and not in late adulthood. Three-point bone bending assays revealed that IGF-1 deficiency early in life resulted in reduced maximum force, maximum bending moment, and bone stiffness in aged males and females. The effects of IGF-1 on bone aging are microenvironment specific, as early-life loss of IGF-1 resulted in decreased cortical bone structure and strength along the diaphysis while significantly increasing trabecular bone fraction and trabecular number at the proximal metaphysis. The increases in trabecular bone were limited to males, as early-life loss of IGF-1 did not alter bone fraction or number in females. Together, our data suggest that the age-related loss of IGF-1 influences tibia bone aging in a sex-specific, microenvironment-specific, and time-dependent manner.

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Acknowledgments

The authors would like to thank Julie Farley and Joanna Hudson for their assistance isolating tissues and Dr. Timothy Griffin for his critical comments on the manuscript. This work was supported by NIH R01AG038747 to WES and the Donald W. Reynolds Foundation.

Author contributions

NMA, JCH, PNE, and ELH performed experiments. NA, JCH, SL, AY, MBH, and WES analyzed data and interpreted results. NMA prepared figures and drafted the manuscript. NMA, JCH, PNE, MBH, and WES edited/revised manuscript. NMA, JCH, PNE, MBH, and WES designed research.

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Authors and Affiliations

  1. Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, 975 NE 10th Street, SLY-BRC 1303, Oklahoma City, OK, 73104, USA

    Nicole M. Ashpole, Sreemathi Logan, Erik L. Hodges, Andriy Yabluchanskiy & William E. Sonntag

  2. Department of Immunology/Rheumatology/Allergy Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Jacquelyn C. Herron & Mary Beth Humphrey

  3. Department of Biomedical Engineering, University of Alabama Birmingham, Birmingham, AL, USA

    Patrick N. Estep

  4. Department of Veteran’s Affairs, Oklahoma City, OK, 73104, USA

    Mary Beth Humphrey

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  1. Nicole M. Ashpole
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  2. Jacquelyn C. Herron
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Correspondence to Nicole M. Ashpole.

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Ashpole, N.M., Herron, J.C., Estep, P.N. et al. Differential effects of IGF-1 deficiency during the life span on structural and biomechanical properties in the tibia of aged mice. AGE 38, 38 (2016). https://doi.org/10.1007/s11357-016-9902-5

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