Healthy Aging

Combating Age-Related Immune Decline: Can Nutrition Help?

A look at nutritional factors that keep immune defenses strong, even in older adults

The immune system is a critical component of health throughout life. However, on the front and back end of the years we spend on this planet, our immune defenses aren’t particularly impressive. In infancy, while the immune system is developing, much of our immune defenses come from breast milk, and when we are elderly, our immune system essentially goes on retirement as well – to some extent it stops learning and doesn’t have the capacity to combat invaders like it once did. This unfortunate decline in immune function with aging is known as immunosenescence.[1],[2],[3]

Clinically, immunosenescence contributes to the increased susceptibility to infections, and the decreased efficacy of vaccines, as we age.[4],[5],[6] About half of individuals over age 65 who are vaccinated for influenza, for example, do not produce enough antibodies to protect against future infections.[7] Thus, while the elderly are in great need of vaccines, at the same time they may have a poorer response.

On the good news side, a myriad of studies suggest that better nutrition can improve immune function at any age, even in those who have already reached senior status.[8],[9],[10]  People who manage to live a long and healthy life typically consume plant-based diets that include a variety of fruits, vegetables, legumes, nuts, and whole grains, and often include fish.[11] Plant-based diets, such as the Mediterranean diet, provide relatively high levels of dietary fiber, antioxidants (including polyphenols), vitamins, and minerals. In a 12-month study of more than 1,200 individuals aged 65–79 years, a Mediterranean diet intervention was shown to improve the gut microbiome, reduce frailty, and enhance innate immune function.[12],[13]

Micronutrient deficiencies contribute to immunosenescence

People who live to be 100 years old are rarely deficient in zinc, suggesting that adequate zinc levels may contribute to their longevity.

Various micronutrients are essential for immunocompetence, including vitamins A, C, D, and E; B vitamins (B2, B6, B12, folic acid); and the minerals iron, selenium, and zinc.[14] A recent study revealed substantial inadequacies in vitamins A, C, D, E, and zinc across the population.[15] Deficiencies of these nutrients increase the risk of infections, especially in the elderly.[14],[16],[17]

Zinc is one of the main micronutrients in this regard.[17],[18],[19] The age-related decline in immunity is controlled in part by thymulin, a zinc-containing hormone produced by the thymus gland that regulates the production and maturation of a type of white blood cell known as the T-lymphocyte, or simply, T cell.[20] Zinc deficiency leads to a decline in T-cell numbers, lower activity of natural killer (NK) cells and cytotoxic T cells, and reduced levels of interferon (a cytokine involved in viral killing).[19],[20] All of these changes impair the ability to fight infections.[21]

Fortunately, correcting zinc deficiency can reverse many of these effects. In older adults, zinc supplementation has been shown to increase the numbers of innate and adaptive immune cells, reduce the risk of respiratory infections, and improve the antibody response to vaccines.[18],[22],[23],[24],[25],[26],[27] People who live to be 100 years old are rarely deficient in zinc, suggesting that adequate zinc levels may contribute to their longevity.[28],[29]

The importance of dietary fiber and the microbiome

One of the best things you can do for your health (at any age) is to consume plenty of fiber.

The gut harbors a diverse microbial community that gradually changes in composition as we age. Populations of friendly bacteria decline, while microbial species associated with inflammation become more abundant.[30],[31],[32],[33] These microbial shifts correlate with poor health in the elderly.30,[34],[35]

Short-chain fatty acids (SCFAs), specifically acetate, propionate, and butyrate, are a well-recognized link between the gut microbiota and the immune system.[36],[37],[38] SCFAs are generated by beneficial microbes, including bifidobacteria, and they have been shown to stimulate the production and activity of various immune cells.[37],[39],[40] As the populations of beneficial bacteria decline with age, there is a corresponding decline in SCFAs, which exacerbates immunosenescence.[41],[42],[43],[44]

Interestingly, SCFAs are almost exclusively derived from bacterial fermentation of non-digestible dietary fiber.[45],[46] In fact, the amount and type of fiber we consume on a daily basis is the most important determinant of SCFA levels.[47],[48],[49],[50] Western diets that emphasize processed foods are associated with low levels of SCFAs, while high-fiber, plant-based diets are associated with healthier amounts of these important metabolites.[51],[52],[53],[54],[55]

High fiber intakes are associated with a lower risk of infectious diseases and mortality from all causes.[56],[57] In healthy volunteers aged 65-85 years with low fruit and vegetable (FV) intakes, increasing FV consumption from two to five servings per day was shown to reduce the risk of infections and boost the response to a pneumonia vaccine.[58] In terms of diet, one of the best things you can do for your health (at any age) is to consume plenty of fiber.[51],[59],[60]

Prebiotics help fill the “fiber gap”

Prebiotic supplementation has been shown to increase the populations of beneficial bacteria and the production of immune-boosting SCFAs at all ages.

Most Americans do not consume enough dietary fiber to meet the needs for good health.[61],[62] The so-called “fiber gap” can trigger a substantial decline in microbial diversity and in beneficial metabolites such as SCFAs.[62]

Prebiotics can help fill the gap, especially for individuals who have difficulty consuming enough fiber on a daily basis.[46] Well-known prebiotics include inulin and various oligosaccharides (small carbohydrates), such as xylo-, galacto-, and fructo-oligosaccharides (XOS, GOS, FOS), which have demonstrated positive health effects in aging and elderly individuals.[63],[64],[65],[66],[67]

Prebiotic supplementation has been shown to increase the populations of beneficial bacteria and the production of immune-boosting SCFAs at all ages.[64],[68],[69],[70],[71],[72] In clinical studies, prebiotic supplementation has been shown to reduce the risk of infections in the elderly.[73],[74],[75] Higher baseline bifidobacteria counts enhance the effects of prebiotics, which explains why prebiotics and probiotics are often combined, as discussed below.[76]

Although they are not strictly classified as prebiotics, plant-derived polyphenols – such as those found in berries and grape seed extracts – have been shown to promote the growth of bifidobacteria.[77],[78],[79] They also have antioxidant effects throughout the body,[80] which is important because antioxidant levels typically decline with age.[81] The consumption of polyphenols has been linked to a reduced risk of many age-related diseases.[3],[82],[83]

Probiotic organisms support a healthy microbiome as we age

Probiotic supplementation has been shown to increase the activity or numbers of immune cells in elderly individuals.

One of the major genera of bacteria in the colon is bifidobacteria, and their decline contributes to poor health and immunosenescence in the aged.[84],[85] By contrast, healthy aging is associated with a greater abundance of these and other beneficial bacteria.[86],[87],[88]

Supplementation with probiotic bifidobacteria, such as B. lactis, B. bifidum and/or B. breve, can help boost bifidobacteria populations in elderly individuals.[89],[90] Also, probiotics are often combined with prebiotics in order to “seed” the microbiome with beneficial bacteria, then “feed” them to help them grow. In a controlled four-week trial in adults with an average age of 71 years, supplementation with a mixture of probiotics and prebiotics (B. lactis, B. bifidum, inulin, and FOS) was shown to increase the abundance and diversity of bifidobacterial populations.[90] 

In a clinical study of volunteers (median age of 69 years) who consumed milk supplemented with B. lactis for three weeks, there were increases in the proportions of total, helper, and activated T cells and NK cells.[91] The greatest improvements were found in individuals who had the poorest immune responses at the beginning of the study; therefore, these aspects of immunosenescence were reversible. Supplementation with bifidobacteria also has been shown to delay immunosenescence in animal models.[92]

Another major class of probiotics, Lactobacillus, is capable of activating immune cells directly by making use of receptors found on the surface of white blood cells.[93],[94],[95] In various studies with elderly individuals, supplementation with L. rhamnosus, L. paracasei, L. casei, and/or or L. plantarum has been shown to increase the activity or numbers of immune cells,[92],[96] reduce the incidence and/or duration of infections,[96],[97],[98],[99],[100] and improve the antibody response to vaccines.[101],[102]

Beta-glucans have unique nutritional properties

Supplementation with yeast β-glucan reduced the incidence and duration of upper respiratory tract infections.

Found in medicinal mushrooms and edible yeast, β-glucan is a polysaccharide that is highly valued for its health-promoting properties. β-glucans from these sources have prebiotic properties, as they have been shown to increase the quantities of bifidobacteria and SCFAs in human studies.[103],[104],[105] β-glucan is also found in baker’s yeast (Saccharomyces cerevisiae) and in a well-known probiotic yeast, Saccharomyces boulardii.[106],[107]

Mushroom and yeast β-glucans can directly activate the immune system.[108],[109],[110] Studies in animal models of aging suggest that β-glucans are capable of boosting adaptive (T cell and antibody-mediated) immunity, thereby counteracting immunosenescence.[111]

Consistent with this finding, a placebo-controlled trial in adults (ages 50 to 68 years) showed that supplementation with yeast β-glucan (250 mg/day for 90 days) increased the ability of blood cells to produce interferon, and reduced the incidence and duration of upper respiratory tract infections.[112] Clinical research of a particular blend of mushroom extracts and natural hemicellulose compounds (which also have similar prebiotic and immune-stimulating effects) also found that this combination boosted immune defenses, including in the immunosuppressed.[113]

S. boulardii serves not only as a probiotic,[114],[115] but also as a prebiotic,[110],[116] and an immunomodulator. The consumption of a nutritional formula containing S. boulardii lysate, colostrum-derived lactoferrin, and other components has been shown to stimulate NK cells in elderly subjects who were immune-compromised.[117] This is an important finding, since an age-associated decline in NK activity contributes to immunosenescence.[21],[118]

S. boulardii is renowned for its ability to ameliorate dysbiosis and diarrhea in individuals taking antibiotics.[103],[119],[120] The consumption of S. boulardii has been shown to reduce the risk of a serious gastrointestinal infection known as Clostridium difficile,[121] which disproportionately affects the elderly.[122],[123],[123]

Summing up

Immunosenescence is strongly influenced by diet and nutrition. Diets that are high in fiber, antioxidants, and other key nutrients help support healthy aging and immunity. Vitamin and mineral supplementation may be important to prevent or correct age-related deficiencies, such as zinc and vitamin D, while grape seed extracts and/or berry polyphenols can help increase levels of antioxidants that are depleted as we age.

The microbiome plays a major role in healthy aging, and it is strongly influenced by dietary fiber. Prebiotics can fill fiber gaps and synergize with probiotics to improve the microbiome.  Probiotic supplementation can help prevent the typical age-related loss of beneficial bacteria, restore a healthy microbiome after antibiotic use, and improve immune responses. Finally, specialized nutrients – such as beta-glucans from mushrooms or yeast – can directly boost immunity, even in the elderly.

If you liked this topic, you may also be interested in the following articles:

Study Identifies Widespread Inadequacies of Immune Health Nutrients
Vaccine Efficacy, Part 1 of 2: Can a Healthy Diet Improve It?
Vaccine Efficacy, Part 2 of 2: Can a Healthy Gut Microbiome Improve It?
The Healthspan Imperative: Why Healthspan is the New Focus of Geroscience

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