The practice of calorie restriction slows aging and extends healthy life, quite dramatically so in short-lived species, and far more modestly in long-lived species. All of the mechanisms of aging, the forms of damage that accumulate in old tissues and the outcomes of that damage, are affected. Some are affected more than others, however. So it is possible to see some aspects of aging that are less robustly responsive to calorie restriction, such as loss of cognitive function, as noted here.
It is interesting to speculate on the specific mechanisms involved in an age-related decline that responds well to life-long calorie restriction, but very poorly to calorie restriction initiated in later life. We know for example that structural damage to the brain occurs in conjunction with vascular aging, meaning increased blood pressure, reduced integrity of the blood-brain barrier, and so forth. The brain regenerates poorly, so this is a form of damage that accumulates over time and will not be remediated by the later adoption of calorie restriction and a corresponding reduction in blood pressure.
Calorie restriction (CR) has been considered the most effective non-pharmacological intervention to counteract aging-related diseases and improve longevity. This intervention has shown beneficial effects in the prevention and treatment of several chronic diseases and functional declines related to aging, such as Parkinson's, Alzheimer's, and neuroendocrine disorders. However, the effects of CR on cognition show controversial results since its effects vary according to intensity, duration, and the period of CR.
Here we present some of the results of the last ten years of studies with CR at different stages of life on neurodegenerative diseases such as Alzheimer's disease. Some investigations associating CR with physical exercise have also been presented. Together this association is the main non-pharmacological strategy to prolong longevity and quality of life. We also presented some substances that mimic the effects of CR and would be potential drugs to mimic the beneficial effects of CR in individuals with some restrictions on intervention. Several studies have also been carried out not only in conventional laboratory animals but also in some wild models since CR can be an environmental factor that interferes with the survival and perpetuation of species.
This information can show the different effects of CR on cognition depending on the period in which it is initiated, its intensity and duration in different animal models, and how it can interfere with the quality of life of individuals. These studies contribute to a better understanding of the mechanisms related to CR in cognition and support future studies with humans. CR may be a potential alternative to the treatment of comorbidities related to mental healthy and cognition.
We conclude that CR between 20% and 40% initiated in the first month of life would attenuate age-related cognitive declines in experimental animals, in healthy and pathological aging, such as in Alzheimer's disease. CR may not reverse the harmful effects of aging on cognition if starts later. In addition, CR also attenuates cognitive deficits resulting from obesity and brain injuries such as traumatic brain. Finally, CR can improve cognition, when performed with moderate intensity and early in life. When performed intensely and later in experimental animals, CR may be deleterious for cognition.