The immune system declines with age, becoming overactive and inflammatory (inflammaging) while at the same time losing its capacity to destroy pathogens and errant cells (immunosenescence), and also becoming dysregulated and harmful in its participate in processes of tissue maintenance. It is well established that the practice of either intermittent fasting or calorie restriction can slow the progression of aging and, specifically, improve the function of the aging immune system. Since these interventions appear to produce their beneficial effects on cell behavior largely through improved autophagy, autophagy should most likely be the starting point for any consideration of how immune function is improved.
Autophagy is a complex set of processes that maintain the health of a cell by recycling excess and damaged proteins and structures, delivering them to a lysosome where they are dismantled into raw materials for further protein synthesis. Many of the approaches shown to modestly slow aging in laboratory species involve improvements in autophagy, as they are all different ways to tinker with the extensive regulatory machinery that controls the cellular response to low nutrient availability.
Up to a point, greater autophagy protects against damage and cell stress, and this adds up over time. Improved autophagy can reduce the pace at which cells become senescent, and thus lower the overall burden of lingering senescent cells in aged tissues. This reduces pro-inflammatory signaling. Similarly, improved autophagy can dampen innate immune reactions to the molecular damage of aging.
Fasting and calorie restriction modulate age-associated immunosenescence and inflammaging
Aging is a complex process, associated with the accumulation of damaged molecules, progressive loss in structure and function of cells, tissues, and organs, and increased vulnerability to death. Even if the aging process is multifaceted and diverse, laboratory manipulation of genes in different laboratory model animals has increased the lifespan of these organisms. Most genes that are associated with increasing lifespan are part of the nutrient-sensing pathway and the mutation in these genes mimics the state of food shortage. Different mechanisms of fasting and calorie restriction (CR) have been linked with healthy aging trajectories in different organisms. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored.
Alongside other systems in the body, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. Of the two systems, the adaptive part of the immune system is most impacted by aging. Inflammation is a crucial process that facilitates the maintenance and restoration of tissue and the clearance of pathogens. On the other hand, chronic inflammatory processes are linked with different pathologies, like rheumatoid arthritis. Aside from this pathological involvement of chronic inflammation, the aging process is linked with a low-grade, chronic, and sterile inflammation (an inflammation without infection) termed as "inflammaging."
In general, evidence-based scientific experiments on fasting and calorie restriction have shown to promote healthy aging as well as to alleviate some markers of immunosenescence and inflammaging. Thus, similar to regular exercise, a vegetarian diet, etc., fasting/calorie restriction should also be considered part of a healthy lifestyle. Furthermore, fasting and calorie restriction increases the fitness of the immune system in fighting infection and cancer which are more common in the elderly. However, more data are needed especially on nutritional approaches including, the amount of nutrients, type of nutrients, and combination of nutrients that promote healthy aging and an effective immune response in humans. Furthermore, strategies on how to integrate fasting/calorie restriction in boosting immune response like the length of the intervention, and at what age is best to start fasting still need to be standardized so that its actual effect on the aging immune system can be clarified and used.
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