GeroScience

, Volume 39, Issue 2, pp 129–145

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

  • Nicole M. Ashpole
  • Sreemathi Logan
  • Andriy Yabluchanskiy
  • Matthew C. Mitschelen
  • Han Yan
  • Julie A. Farley
  • Erik L. Hodges
  • Zoltan Ungvari
  • Anna Csiszar
  • Sixia Chen
  • Constantin Georgescu
  • Gene B. Hubbard
  • Yuji Ikeno
  • William E. Sonntag
Original Article

DOI: 10.1007/s11357-017-9971-0

Cite this article as:
Ashpole, N.M., Logan, S., Yabluchanskiy, A. et al. GeroScience (2017) 39: 129. doi:10.1007/s11357-017-9971-0

Abstract

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igff/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Keywords

Insulin-like growth factor-1 Somatomedin C Aging Longevity Cancer Pathology 

Supplementary material

11357_2017_9971_MOESM1_ESM.pdf (992 kb)
ESM 1(PDF 991 kb)

Funding information

Funder NameGrant NumberFunding Note
National Institute on Aging
  • R01-AG038747
  • R01-AG047879
  • F32-AG048728
American Federation for Aging Research
    Ellison Medical Foundation
      Arkansas Claude Pepper Older Americans Independence Center
      • P30-AG028718
      Oklahoma Center for the Advancement of Science and Technology
        San Antonio Nathan Shock Center
          Oklahoma Nathan Shock Center
          • P30-AG050911
          Donald W. Reynolds Foundation

            Copyright information

            © American Aging Association 2017

            Authors and Affiliations

            • Nicole M. Ashpole
              • 2
            • Sreemathi Logan
              • 1
            • Andriy Yabluchanskiy
              • 1
            • Matthew C. Mitschelen
              • 1
            • Han Yan
              • 1
            • Julie A. Farley
              • 1
            • Erik L. Hodges
              • 1
            • Zoltan Ungvari
              • 1
            • Anna Csiszar
              • 1
            • Sixia Chen
              • 3
            • Constantin Georgescu
              • 4
            • Gene B. Hubbard
              • 5
              • 6
            • Yuji Ikeno
              • 5
              • 6
            • William E. Sonntag
              • 1
            1. 1.Reynolds Oklahoma Center on Aging, Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
            2. 2.Department of BioMolecular SciencesUniversity of MississippiOxfordUSA
            3. 3.Department of Biostatistics and EpidemiologyUniversity of Oklahoma Health Sciences CenterOklahomaUSA
            4. 4.Oklahoma Medical Research FoundationOklahomaUSA
            5. 5.The Barshop Institute for Longevity and Aging Studies and Department of PathologyThe University of Texas Health Science Center at San AntonioSan AntonioUSA
            6. 6.Research ServiceAudie L. Murphy VA HospitalSan AntonioUSA

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