title: Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice.
abstract: Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF-1R), the cells of the supraoptic nucleus (SON) display some of the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22 months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each section of supraoptic hypothalamus. Results show that while the total number of cells in the SON of ad-libitum fed mice does not change significantly with aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad-libitum fed mice with aging. In contrast to this, calorie restricted mice show both a decline in the total number of cells and IGF-1R immunoreactive cells in the SON with age, but with the decrease in the latter being notably attenuated when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR induces greater loss in the total number of cells in the SON with age, it reduces the degree of age-dependent loss seen in IGF-1R expressing cells. As a result, when compared to Old-AL mice, the SON of Old-CR mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging.
authors.affiliation: Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Yaghmaie
authors.forename: O
authors.initials: O
authors.lastname: Saeed
authors.forename: S A
authors.initials: SA
authors.lastname: Garan
authors.forename: M A
authors.initials: MA
authors.lastname: Voelker
authors.forename: A M
authors.initials: AM
authors.lastname: Gouw
authors.forename: W
authors.initials: W
authors.lastname: Freitag
authors.forename: H
authors.initials: H
authors.lastname: Sternberg
authors.forename: P S
authors.initials: PS
authors.lastname: Timiras
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D002452:Cell Count / Q000379:methods; D007032:Hypothalamus, Anterior / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*
chemical_list: D007334:Insulin-Like Growth Factor I