Resting state fMRI reveals differential effects of glucose administration on central appetite signalling in young and old adults

Background: Healthy aging has been associated with reduced appetite and lower energy intake, which can lead to loss of bodyweight, undernutrition and related health problems. The causes for the decline in caloric intake are multifactorial, involving physiological and non-physiological processes. Aims: Here we examined the effect of glucose on brain function in healthy adults as well as age-related, physiological changes in brain responses associated with macronutrient intake. Methods: Using a randomized, double-blind, balanced cross-over design, younger (n = 16, aged 21–30) and older (n = 16, aged 55–78) adults received a drink containing glucose and a taste-matched placebo after an overnight fast. Blood glucose and hunger were assessed at baseline and 20 min post-ingestion, after which participants underwent resting state functional magnetic resonance imaging. Results: Frequency-dependent changes associated with glucose administration in slow-5 (0.01–0.027 Hz) and slow-4 (0.027–0.073 Hz) amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) of the blood oxygen level-dependent (BOLD) signal were investigated within the young healthy adults, and then extended to the older age group. Consistent with previous reports, glucose decreased amplitude in slow-5 fALFF within the left orbitofrontal cortex and insular cortex in the young adults. We observed a significant interaction in slow-5 ALFF and fALFF in the left insula, such that younger participants showed a decrease in BOLD amplitude, whereas older participants showed an increase, after glucose administration. We further observed an interaction in slow-4 ALFF in the occipital region and precuneus, with older participants showing an increase in magnitude of slow-4 ALFF and younger participants showing a decrease in the same measure. Conclusion: These age-related, frequency-dependent changes in the magnitude of the BOLD signal in the insula, a key region related to energy homeostasis following feeding, may point to a change in satiety or homeostatic signalling contributing to behavioural changes in energy intake during senescence.