Aging is associated with a multitude of metabolic changes that increase the incidence of acute and chronic neurological disorders. Cerebral metabolism requires a large quantity of energy. Mitochondria, the cellular organelles responsible for energy production, are particularly affected in older brain tissue. Impaired mitochondria generate less energy and emit toxic byproducts that further harm the brain.
Our research team studies the role of cellular metabolism and, more specifically, modulators of mitochondrial function, in brain aging and in age-related neurological disorders. Our research focuses mainly on Alzheimer’s disease. Within this context, we have discovered that ketones, a group of physiological compounds that are produced by the liver after fasting or consumption of the low-carbohydrate, high-fat ketogenic diet, protect neurons in various models of neurological disease by enhancing mitochondrial function.
Our efforts are aimed at characterizing the neuroprotective properties of ketones in acute and chronic neurological disorders and at identifying underlying molecular mediators that will be amenable to pharmacological intervention. We are focusing on sirtuins, a family of enzymes implicated in cellular metabolism and survival.
Our research team has shown that the activity of mitochondria, the principal sources of cellular energy, decreases as the brain ages. In experimental models, mitochondrial activity is further impaired when the biochemical and pathological changes that occur in Alzheimer’s disease and in Parkinson’s disease are replicated.
In our model of Alzheimer’s disease, the worsening of mitochondrial function was attributed to amyloid beta, a small protein fragment that is increased in the brains of patients affected by the disease. We were the first to demonstrate that enhancing mitochondrial function using ketones, a family of physiological compounds that are naturally produced by the liver after fasting or consumption of a low-carbohydrate, high-fat ketogenic diet, alleviates the toxic effects of amyloid beta and improves neuronal health.
Our research is funded by the Barrow Neurological Foundation and by the Arizona Department of Health Services through the Arizona Alzheimer Consortium.