Chilean scientists have identified a particular mechanism underpinning how ketogenic diets improve brain performance in older male mice – raising questions about the role of diet in ageing and brain health.
Research at Universidad de Chile, published in Cell Reports Medicine, found cycling male mice between a control diet and ketogenic diet improves signalling that occurs between synapses in the brain.
The ‘keto diet’ focuses on foods that provide lots of healthy fats, adequate amounts of protein and very few carbohydrates; the goal is to get more calories from fat than carbs. It works by depleting the body’s sugar reserves; as a result, it will start to break down fat for energy, triggering production of molecules called ‘ketones’ that the body uses for fuel; when the body burns fats, it can also lead to weight loss.
Previous US research had shown giving male mice a cyclic ketogenic diet reduced their midlife risk of death and prevented memory decline associated with normal ageing.
Chilean lead author Professor Christian González-Billault told medicalnewstoday.com the previous studies showed ‘improvement in specific behavioural tasks routinely used in animal experimentation to evaluate memory and learning.
‘Such an improvement convinced us to go deeper into the molecular mechanisms that explain that positive response on one side, but also prompted us to include several other assessments at different levels, ranging from the whole organism level to the molecular functions, to understand why the diet was beneficial in aged animals.’
They kept 19 male mice aged 20-23 months (‘old age’ in mice) on a control diet or a ketogenic diet cycled with the control diet every other week; for 12 weeks the metabolic parameters of the mice were measured, and for 5 weeks after that mice were kept on their diets and subjected to behavioural testing.
Results indicated the ketogenic diet was associated with lower blood sugar and improved memory and motor ability in older mice, with improved plasticity in the hippocampus brain region of older mice. Further testing showed this improved plasticity in mice kept on a ketogenic diet cycled with a control diet was due to a molecule called a ‘ketone body’ (produced when levels of glucose are low), activating a signalling pathway between the synapses.
Professor González-Billault noted: ‘We focused our attention on aged mice because previous work showed the effect of the diet in young animals was milder and, in some cases, did not show significant differences with a control diet. These antecedents suggest one of the beneficial roles of the diet would be maintaining resilience in aged mice, improving their physiological functions as they age.
‘This concept is fundamental in the ageing field because it relates to the difference between lifespan (all our vital trajectory from birth to death) and healthspan (the part of our vital trajectory free from chronic diseases).’
He also noted: ‘Why this is not happening when animals are younger still merits more study. However, we could speculate internal resilience mechanisms present while we are young are enough to compensate for or overcome damage induced in cells, tissues, organs and the organism.’
