Calorie restriction, also known as dietary restriction in the scientific community, is the practice of consuming up to 40% fewer calories than usual, while still obtaining optimal levels of micronutrients. It produces sweeping changes in the operation of cellular metabolism, slows near all measures of aging, and extends life in mice. Thus for any particular aspect of aging, and here the focus is on chronic inflammation in the brain that accelerates progression of age-related neurodegeneration, it is possible to invest a great deal of time and effort into investigating just how calorie restriction slows it down.
This sort of work is of great scientific interest, as it will help researchers to build a comprehensive map of cellular metabolism and the changes that take place over the course of aging. It is not, however, a road to rejuvenation. Calorie restriction, like all approaches involving upregulation of cellular stress responses, has a much smaller effect on life span in humans than in short-lived species such as mice. There isn't a way to conjure a reversal of aging in the elderly from this biochemistry. That requires a completely different strategy, based on identification of root cause damage, and repair of that damage, as outlined in the SENS roadmap for development of rejuvenation therapies.
A growing body of evidence demonstrates that dietary restriction (DR) exerts its beneficial effects on brain aging at multiple levels. Although there is some degree of discrepancy across studies, likely due to the difference in the model organisms and experimental design, DR appears to mitigate all of the morphological and functional alterations in the brain associated with aging. A major hallmark of aging is systemic, low-grade chronic inflammation throughout the body, termed inflammaging. Notably, these inflammatory signs are similar to the ones associated with obesity and metabolic diseases, providing a possible glimpse into why DR exerts anti-inflammatory effects on aging-associated inflammation.
As with other organs, chronic low-grade inflammation is a common feature of the aged brain. Neuroinflammation is a host defense mechanism against harmful stimuli and damage in the brain. However, chronic inflammation can be deleterious in normal aging as well as in pathological aging related to neurodegenerative diseases. The central nervous system (CNS) is composed of heterogeneous cell types, including neurons, microglia, astrocytes, and oligodendrocytes. Although two major glial cell types, astrocytes and microglia, are known to be key players in inflammatory responses in the brain, it is now well recognized that all neural cells participate to some degree in the neuroinflammatory responses.
Neuroinflammation often manifests as astrogliosis, microgliosis, and an increase in secreted inflammatory mediators, such as cytokines, chemokines, and complement proteins. Accumulating evidence from clinical and basic research suggests that neuroinflammation is tightly connected to the decline in brain function during aging. Although the precise mechanisms of DR's neuroprotective functions are not fully elucidated, it has been suggested that DR exerts neuroprotective effects through multiple pathways, such as modulating metabolic rates, reducing oxidative stress, increasing anti-inflammatory responses, regulating insulin sensitivity, and improving synaptic plasticity and neurogenesis. All of the molecular changes induced by DR may directly or indirectly contribute to the regulation of neuroinflammation associated with aging and neurodegenerative diseases. DR may directly mitigate activation of glial cells and modulate expression of inflammatory cytokines and indirectly regulate neuroinflammation by reducing inflammatory stresses, such as accumulation of toxic proteins and oxidative stress.