|Tracking changes in hypothalamic IGF-1 sensitivity with aging and caloric restriction.
F. Yaghmaie , O. Saeed , S.A. Garan , A.M. Gouw , P. Jafar , J. Kaur , S. Nijjar , P.S. Timiras , H. Sternberg , M.A. Voelker .  Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA,  New York Medical College, Valhalla, New York, USA,  Aging Research Centre, Waterloo, Ontario, Canada,  Department of Molecular and Cell Biology, University of California, Berkeley, USA,  BioTime, Inc., Berkeley, California, USA
Manipulating IGF-1 signaling in the neuroendocrine system reliably extends the mammalian lifespan, yet the basic descriptive biology concerning IGF-1 Receptor (IGF-1R) density and distribution throughout the lifespan is lacking. By tracking changes in hypothalamic IGF-1 sensitivity with both normal aging and life-long caloric restriction, the IGF-1R biomarkers of aging can be determined while simultaneously evaluating the role of IGF-1 signaling in CR’s life extending effect. Of the hypothalamic nuclei that express IGF-1 Receptor (IGF-1R), the cells of the Supraoptic nucleus (SON) and Paraventricular nucleus (PVN) display the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, this investigation counted IGF-1R-immunoreactive and non-immunoreactive cells in the SON and PVN 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 hypothalamus. Results show that both SON and PVN lose about one-third of IGF-1R immunoreactive cells with normal aging. Also, Old-CR mice lost higher numbers of IGF-1R non-immunoreactive cells while maintaining similar counts of IGF-1R immunoreactive cells in comparison to Old-Al mice. Consequently, Old-CR mice show a higher percentage of IGF-1R immunoreactive cells reflecting increased hypothalamic sensitivity to IGF-1 in comparison to normally aging mice. Supported by NIH AG19145-05 and BioTime, Inc.