Diet modulates brain network stability, a biomarker for brain aging, in young adults
Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether die...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2020
|
| _version_ | 1797104453700026368 |
|---|---|
| author | Mujica-Parodi, LR Amgalan, A Sultan, SF Antal, B Sun, X Skiena, S Lithen, A Adra, N Ratai, E-M Weistuch, C Govindarajan, ST Strey, HH Dill, KA Stufflebeam, SM Veech, RL Clarke, K |
| author_facet | Mujica-Parodi, LR Amgalan, A Sultan, SF Antal, B Sun, X Skiena, S Lithen, A Adra, N Ratai, E-M Weistuch, C Govindarajan, ST Strey, HH Dill, KA Stufflebeam, SM Veech, RL Clarke, K |
| author_sort | Mujica-Parodi, LR |
| collection | OXFORD |
| description | Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (D-β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain. |
| first_indexed | 2024-03-07T06:34:01Z |
| format | Journal article |
| id | oxford-uuid:f6fc8cbb-c3de-4269-a87d-eb76f4fa135a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:34:01Z |
| publishDate | 2020 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:f6fc8cbb-c3de-4269-a87d-eb76f4fa135a2022-03-27T12:39:17ZDiet modulates brain network stability, a biomarker for brain aging, in young adultsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f6fc8cbb-c3de-4269-a87d-eb76f4fa135aEnglishSymplectic ElementsNational Academy of Sciences2020Mujica-Parodi, LRAmgalan, ASultan, SFAntal, BSun, XSkiena, SLithen, AAdra, NRatai, E-MWeistuch, CGovindarajan, STStrey, HHDill, KAStufflebeam, SMVeech, RLClarke, KEpidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (D-β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain. |
| spellingShingle | Mujica-Parodi, LR Amgalan, A Sultan, SF Antal, B Sun, X Skiena, S Lithen, A Adra, N Ratai, E-M Weistuch, C Govindarajan, ST Strey, HH Dill, KA Stufflebeam, SM Veech, RL Clarke, K Diet modulates brain network stability, a biomarker for brain aging, in young adults |
| title | Diet modulates brain network stability, a biomarker for brain aging, in young adults |
| title_full | Diet modulates brain network stability, a biomarker for brain aging, in young adults |
| title_fullStr | Diet modulates brain network stability, a biomarker for brain aging, in young adults |
| title_full_unstemmed | Diet modulates brain network stability, a biomarker for brain aging, in young adults |
| title_short | Diet modulates brain network stability, a biomarker for brain aging, in young adults |
| title_sort | diet modulates brain network stability a biomarker for brain aging in young adults |
| work_keys_str_mv | AT mujicaparodilr dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT amgalana dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT sultansf dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT antalb dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT sunx dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT skienas dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT lithena dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT adran dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT rataiem dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT weistuchc dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT govindarajanst dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT streyhh dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT dillka dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT stufflebeamsm dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT veechrl dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults AT clarkek dietmodulatesbrainnetworkstabilityabiomarkerforbrainaginginyoungadults |