期刊
GEROSCIENCE
卷 39, 期 2, 页码 129-145出版社
SPRINGER
DOI: 10.1007/s11357-017-9971-0
关键词
Insulin-like growth factor-1; Somatomedin C; Aging; Longevity; Cancer; Pathology
资金
- National Institute on Aging [R01-AG038747, R01-AG047879, F32AG048728]
- American Federation for Aging Research (AFAR Breakthroughs in Gerontology Award)
- Ellison Medical Research Foundation Senior Scholar Award
- Arkansas Claude Pepper Older Americans Independence Center at University of Arkansas Medical Center [P30 AG028718]
- Oklahoma Center for the Advancement of Science and Technology
- San Antonio Nathan Shock Center Pathology Core [P30 AG013319]
- Oklahoma Nathan Shock Center of Excellence in the Biology of Aging [P30 AG050911]
- Donald W. Reynolds Foundation
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 igf(f/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.
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