Physical Activity and Diet Shape the Immune System during Aging

Abstract

With increasing age, the immune system undergoes a remodeling process, termed immunosenescence, which is accompanied by considerable shifts in leukocyte subpopulations and a decline in various immune cell functions. Clinically, immunosenescence is characterized by increased susceptibility to infections, a more frequent reactivation of latent viruses, decreased vaccine efficacy, and an increased prevalence of autoimmunity and cancer. Physiologically, the immune system has some adaptive strategies to cope with aging, while in some settings, maladaptive responses aggravate the speed of aging and morbidity. While a lack of physical activity, decreased muscle mass, and poor nutritional status facilitate immunosenescence and inflammaging, lifestyle factors such as exercise and dietary habits affect immune aging positively. This review will discuss the relevance and mechanisms of immunoprotection through physical activity and specific exercise interventions. In the second part, we will focus on the effect of dietary interventions through the supplementation of the essential amino acid tryptophan, n-3 polyunsaturated fatty acids, and probiotics (with a special focus on the kynurenine pathway).

Keywords: aging; exercise; immunosenescence; inflammaging; kynurenine pathway; nutrition.

Figure 1

Immune changes in the innate and adaptive immune system during aging in inactive individuals and in response to a physically active lifestyle.

Figure 2

Aging-associated increases in indoleamine 2,3-dioxygenase (IDO). The process of aging involves proinflammatory pathways, in which the formation of Th1-type cytokine interferon-γ (IFN-γ) is of the utmost relevance. IFN-γ stimulates several enzymes, including indoleamine 2,3-dioxygenase-1 (IDO), which degrades tryptophan into kynurenine, an integral defense mechanism in the cell-mediated immune response. In addition to its role in innate immunity, the kynurenine pathway also plays a role in the regulation of the immune response by slowing down T-cell proliferation. Some tryptophan catabolites have been shown to be involved in the feedback inhibition of T-cell activation via regulatory T-cells, and thus immunosuppression. A supply of certain nutrients and bioactive compounds (such as antioxidants, n-3 PUFAs, or probiotics) can suppress (“−”) IDO activity and slow down Th1-type immune activation cascades. On the other hand, physical exercise stimulates the (“+”) induction of IDO, which is associated with an accelerated tryptophan breakdown and an increased kynurenine/tryptophan ratio [76]. Kynurenine metabolites can affect the brain and several other organs in peripheral tissues, where they induce local and systemic adaptations (see the main text for a description) [67]. Therefore, it is likely that kynurenine and its metabolites may contribute to the mediation of the health benefits of exercise and nutritional supplements.