title: Calorie restriction reduces the influence of glucoregulatory dysfunction on regional brain volume in aged rhesus monkeys.
abstract: Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19-31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships.
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
authors.forename: Auriel A
authors.initials: AA
authors.lastname: Willette
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.forename: Ricki J
authors.initials: RJ
authors.lastname: Colman
authors.forename: Erik K
authors.initials: EK
authors.lastname: Kastman
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Field
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Alexander
authors.forename: Aadhavi
authors.initials: A
authors.lastname: Sridharan
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Rozalyn
authors.initials: R
authors.lastname: Anderson
authors.forename: Mary-Lou
authors.initials: ML
authors.lastname: Voytko
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Kemnitz
authors.forename: Richard H
authors.initials: RH
authors.lastname: Weindruch
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism; D031204:Caloric Restriction; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin; D008253:Macaca mulatta; D008297:Male; D015398:Signal Transduction
chemical_list: D007328:Insulin; D005947:Glucose