Intermittent Fasting is Protective Against the Effects of Vascular Aging in the Brain

Researchers here show that, in mice, intermittent fasting can protect against the damage done by cardiovascular aging that leads to a reduced blood supply to the brain. Forms of calorie restriction, such as intermittent fasting, are generally beneficial for long term health. This is well demonstrated in both mice and humans, though only short-lived species exhibit significant gains in life span as a result. It is interesting to note the opinion that intermittent fasting may be better than straight calorie restriction when it comes to mitigation of pathological mechanisms in neurodegenerative conditions.

Vascular cognitive impairment (VCI) embodies a spectrum of cognitive deficits that range from mild cognitive impairment to vascular dementia (VaD). VCI is associated with cerebrovascular diseases that arise from vascular pathological processes such as atherosclerosis, microvascular protein deposits, haemorrhages and microbleeds. These vascular pathologies lead to a state of reduced blood flow to the brain that is referred to as chronic cerebral hypoperfusion (CCH). Decreased cerebral perfusion has been reported to correlate with dementia severity, and has shown to be a predictive marker to identify individuals with mild cognitive impairment who develop dementia. CCH induces a cascade of cellular and molecular mechanisms that contributes to the pathogenesis of VCI - including oxidative stress and inflammation.

Intermittent fasting (IF) is defined as an eating pattern that cycles between periods of eating and fasting. IF has been extensively reported to extend both health and lifespan, and decrease the development of age-related disorders including cardiovascular, metabolic, and neurodegenerative diseases. Recently, IF has gained much interest as being more effective than caloric restriction for inducing neuroprotective effects in the brain.

In this study, we demonstrate for the first time that IF promotes neuroprotective effects in a model of VaD by maintaining the integrity of the neurovascular structures in the brain. We specifically show that IF attenuated vascular pathology by reducing microvascular leakage and blood-brain barrier dysfunction, while maintaining the expression of tight junction (TJ) proteins. IF was also effective in decreasing white matter lesion formation, hippocampal neuronal cell death and cell death markers, while maintaining myelin basic protein levels. Our data suggest that the effects of IF on the structural integrity of the neurovasculature may be mediated through mechanisms that decrease oxidative stress and matrix metalloproteinase expression. Overall, our findings indicate that prophylactic IF may be a potential therapy in reducing and preventing neurovascular pathology associated with VaD.