Age-associated alterations in immune function and inflammation.

Immunosenescence is a term used to describe the age-related changes in the immune system. Immunosenescence is associated with complex alterations and dysregulation of immune function and inflammatory processes. Age-related changes in innate immune responses including alterations in chemotactic, phagocytic, and natural killing functions, impaired antigen presenting capacity, and dysregulated inflammatory response have been described. The most striking and best characterized feature of immunosenescence is the decline in both number and function of T cells. With age there is decreased proliferation, decreased number of antigen-naïve T cells, and increased number of antigen-experienced memory T cells. This decline in naïve T cell population is associated with impaired immunity and reduced response to new or mutated pathogens. While the absolute number of peripheral B cells appears constant with age, changes in B cell functions including reduced antibody production and response and cell memory have been described. However, the main alteration in cell-mediated function that has been reported across all species with aging is those observed in in T cell. These T cell mediated changes have been shown to contribute to increased susceptibility to infection and cancer in older adults. In addition to functional and phenotype alterations in immune cells, studies demonstrate that circulating concentrations of inflammatory mediators in older adults are higher than those of young. This low grade, chronic inflammatory state that occurs in the context of aging has been termed "inflammaging". This review will focus on age-related changes in the immune system including immunosenescence and inflammation as well as the functional consequences of these age-related alterations for the aged.

Regulatory role of vitamin E in the immune system and inflammation.

Vitamin E, a potent lipid-soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell-based, pre-clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α-tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non-α-alpha-tocopherol vitamin E on immune cell function as well as their potential clinical application. © 2018 IUBMB Life, 71(4):487-494, 2019.

Perspective: Should Vitamin E Recommendations for Older Adults Be Increased?

Current vitamin E requirements are uniformly applied across the population for those >14 y of age. However, aging is associated with alterations in cellular and physiologic functions, which are affected by vitamin E. Therefore, it is questionable whether vitamin E requirements can be uniformly applied to all adult age categories. With aging, there is dysregulation of the immune system in which there are decreased cell-mediated and pathogen defense responses coupled with an overactive, prolonged inflammatory state. Both animal and human studies in the aged suggest that intake above currently recommended levels of vitamin E may improve immune and inflammatory responses and be associated with a reduced risk of infectious disease. We review the evidence that was considered in establishing the current requirements for vitamin E and highlight data that should be considered in determining the vitamin E requirements in older adults, particularly focusing on the evidence suggesting a benefit of increased vitamin E intake on immune function and inflammatory processes and resistance to infection. The main objective of this Perspective is to initiate the discussion of whether the current Dietary Reference Intake for vitamin E should be increased for the older population. We make this suggestion on the basis of mechanistic studies showing biological plausibility, correction of a major cellular dysfunction in older adults, and strong evidence from several animal and a few human studies indicating a reduction in risk and morbidity from infections.