Senescent cells are alive and metabolically active, but are no longer capable of dividing and functioning in a normal way. They evade the body’s natural process of disposing of damaged cells, lingering around secreting inflammatory compounds, increasing inflammation and damaging neighboring cells. According to research published in 2021 in the journal Nature, senescent immune cells are among some of the most harmful senescent cells because they are found throughout the body, exposing organs and tissues to inflammation and triggering senescence in other cells, overall, pushing the aging process into overdrive.¹

In short, immunosenescence leads to a decline in immune function, while also increasing inflammation and the risk for developing a number of diseases associated with aging, including autoimmune diseases and cancer. But as one research paper put it, aging is a malleable process and can be influenced by outside factors.² Indeed, immunosenescence is strongly influenced by diet, nutrition, and other lifestyle factors like exercise.

The Power of Diet & Exercise

A lack of physical activity, decreased muscle mass (frailty), and poor nutrition exacerbate immunosenescence and “inflammaging,” while regular physical movement and a healthy diet support healthy immune aging (no surprises there, right?). Research has shown that improving nutrition, including increasing micronutrients like zinc, leads to better immune health, even in older adults. One recent study investigated the effects of the Mediterranean diet plus vitamin D supplementation in a group of adults aged 65-79. The group followed the Med diet and took a low-dose vitamin D supplement (400 IU) for one year; the follow-up found that those who adhered to the diet and supplements saw improvements in immune function, including a reduction in inflammatory molecules, with the most significant improvements seen in women.³ A Mediterranean-like diet consists of an abundance of fruit and vegetables, fresh herbs, healthy fats like olive oil, nuts and seeds, and small amounts of protein, including fish.

We all know that regular physical activity is fundamental to good health, no matter what age you are, and the benefits extend to the immune system. Research has shown that regular exercise influences the aging process of both the innate and adaptive parts of the immune system, reducing the number of senescent immune cells, inducing cell death in apoptosis-resistant senescent T-cells, enhancing overall immune function, and reducing inflammation. On the other hand, a loss of muscle mass and frailty from inactivity increases immunosenescence, which drives even more loss of muscle.^{4 5} The takeaway? Prioritize regular physical activity that includes both aerobic and resistance training.

The Power of Supplements

Optimize foundational immune nutrients

As so many of us have learned over the past two years, there are a number of micronutrients that are critical for immune health, or immunocompetence. Vitamins and minerals like zinc and selenium and vitamins A, C, E, and D, and the B vitamins are essential for our immune systems to function properly. An inadequacy in any of these can impair immune function and weaken the immune response. And inadequacy is prevalent: A study published in 2020 reviewed data from 26,282 adults and found that “…the prevalence of inadequacy … in four out of five key immune nutrients is substantial.” Forty-five percent of adults had inadequate vitamin A; 46 percent for vitamin C; a whopping 95 percent for vitamin D; 84 percent for vitamin E; and 15 percent for zinc.⁶ This review included adults over the age of 19—we know that older adults and the elderly frequently suffer not only from micronutrient deficiencies, but also from malnutrition, which further impairs immune function.⁷

Other research has shown that people who live to their 90s and 100s have higher levels of zinc and selenium, indicating that these nutrients support healthy aging of the immune system.⁸ A long-term study conducted in France among men and women (average age was 84) living in nursing homes found that low-dose supplementation with zinc (20 mg) and selenium (100 mcg) reduced respiratory tract infections after two years; nutrient deficiencies were corrected after six months.⁹ It is especially important for older folks to fortify their immune systems by ensuring they get optimal amounts of these immune nutrients with a healthy diet and supplementation. A multivitamin and mineral supplement is an excellent way to correct insufficiencies, with targeted supplementation of individual nutrients as needed.

The foundational immune nutrients are a critical piece in supporting optimal immune health and slowing immunosenescence, but there is a plethora of targeted nutritional support that should also be considered.

Reduce inflammation

Because immunosenescent cells secrete a variety of pro-inflammatory molecules throughout the body, pushing the body into an inflammatory state (which will eventually result in disease), reducing chronic inflammation is a must. The omega-3s DHA and EPA have a vast body of research behind them as being one of the best nutrients available for reducing inflammation, and research has also shown that these anti-inflammatory fats promote healthy immune cell function in both the innate and adaptive immune systems.¹⁰ Curcumin, the main bioactive constituent in the spice curcumin, is also supported by a large body of research proving its effectiveness as an anti-inflammatory nutraceutical. Its powerful anti-inflammatory actions appear to be related to its ability to inhibit the activity of nuclear factor kappa B (NF-ĸB), a “master regulator of the inflammatory process.” In addition to its powerful anti-inflammatory actions, curcumin is also an antioxidant, protecting cells from oxidative damage (another driving force behind the aging process) and enhancing our bodies’ own antioxidant defenses.¹¹

Polyphenols are a large group of phytochemicals found in fruits, vegetables, and other plant foods that reduce inflammation and oxidative damage; the consumption of polyphenols has been linked to a reduced risk of a number of chronic inflammatory-related diseases (one of the reasons it’s so important to eat lots of vegetables and fruit). In addition to their anti-inflammatory and antioxidant properties, some polyphenols have been identified as “senolytic agents,” a class of molecules that can selectively induce death in senescent cells, helping to reduce immunosenescence. Resveratrol and quercetin are two such polyphenols (curcumin is another one).¹² Resveratrol and quercetin have also been shown to counteract the inflammation produced by senescent cells and support a healthy immune response.^{13 14}

Improve gut health

Another change that comes with age is a change in our gut bacteria, with a decline in diversity and a shift to more inflammatory bacteria, which is associated with poor health in older people. Because 70 to 80 percent of our immune cells are located in our guts, it is critically important to support a healthy balance of gut bacteria, especially as we grow older.^{15 16} One simple way to do this is eat more fiber, found in, you guessed it, fruit and vegetables. Fiber acts as food for healthy bacteria and can improve overall gut health. To fill in the so-called “fiber gap,” consider supplementing with pre-biotics, such as chia seeds, psyllium, FOS, and inulin, which also serve as food for good bacteria and will help them thrive and proliferate.

One of the beneficial bacterial groups that older folks commonly see a reduction in is Bifidobacteria, including B. lactis, B. bifidum, and B. breve. Supplementing with a probiotic that contains these bacteria can increase levels in older people, as well as improve immune function.^{17 18} One animal study even found that B. bifidum has anti-senescent effects.¹⁹ Another common group of bacteria is Lactobacillus, including L. rhamnosus, L. casei, and L. plantarum, is known to have immunomodulating effects, and supplementation with these has been found to improve immune function in older people.^{20 21} These strains are commonly found in most probiotic supplements.

Immunosenescence is a hallmark of aging and age-related decline, but aging is a pliable thing, greatly influenced by diet and lifestyle. The good news is that the very things that support overall health—a healthy diet rich in vegetables, regular exercise, and targeted supplements—are the same things that can combat immunosenescence, ensuring that you have a long and vibrant healthspan to look forward to.

Refrences

1. Yousefzadeh MJ, Flores RR, Zhu Y, et al. “An aged immune system drives senescence and ageing of solid organs.” Nature. 2021 Jun; 594(7861): 100-105. doi: 10.1038/s41586-021-03547-7
2. Aiello A, Farzaneh F, Candore G, et al. ”Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention.” Front Immunol. 25 September 2019.  https://doi.org/10.3389/fimmu.2019.02247
3. Maijo M, Ivory K, Clements SJ, et al. “One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3 Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype, Co-receptor Expression and Innate Immune Responses in Health Elderly Subjects: Results From the United Kingdom Arm of the NU-AGE Trial.” Front Physiol. 26 Jul 2018; 9:997. doi: 10.3389/fphys.2018.00997
4. Weyh C, Kruger K, and Strasser B. “Physical Activity and Diet Shape the Immune System during Aging.” Nutrients. 202 Mar; 12(3): 622 doi: 10.3390/nu12030622
5. Spielmann G, McFarlin BK, O’Connor DP, et al. “Aerobic fitness is associated with lower proportions of senescent blood T-cells in man.” Brain, Behavior, and Immunity. Nov 2011; 25(8): 1521-1529 https://doi.org/10.1016/j.bbi.2011.07.226
6. Reider CA, Chung R-Y, Devarshi PP, et al. “Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES.” Nutrients. 2020 Jun; 12(6): 1735 doi: 10.3390/nu12061735
7. Norman K, Hab U, and Pirlich M. “Malnutrition in Older Adults—Recent Advances and Remaining Challenges.” Nutrients. 2021 Aug; 13(8): 2764 https://doi.org/10.3390/nu13082764
8. Savarino L, Granchi D, Ciapetti G, et al. “Serum concentrations of zinc and selenium in elderly people: results in healthy nonagenarians/centenarians.” Exp Gerontol. 2001 Feb;36(2):327-39. doi: 10.1016/s0531-5565(00)00218-7
9. Girodon F, MD, PhD; Galan P, MD; Monget A-L, PhD, et al. “Impact of Trace Elements and Vitamin Supplementation on Immunity and Infections in Institutionalized Elderly Patients” Arch Intern Med. 1999; 159(7): 748-754 doi:10.1001/archinte.159.7.748
10. Gutierrez S, Svahn SL, and Johansson ME. “Effects of Omega-3 Fatty Acids on Immune Cells.” Int J Mol Sci. 2019 Octo; 20(20); 5028 doi: 10.3390/ijms20205028
11. Sikora E, Scapagnini G, Barbagallo M. Curcumin, inflammation, ageing and age-related diseases. Immun Ageing. 2010 Jan 17;7(1):1. doi: 10.1186/1742-4933-7-1. PMID: 20205886; PMCID: PMC2827376.
12. Santos JC, Riberio ML, and Gambero A. “The Impact of Polyphenols-Based Diet on the Inflammatory Profile in COVID-19 Elderly and Obese Patients.” Front Physiol. 12 Jan 2021; https://doi.org/10.3389/fphys.2020.612268
13. Malaguarnera L. Influence of Resveratrol on the Immune Response. Nutrients. 2019 Apr 26;11(5):946. doi: 10.3390/nu11050946. PMID: 31035454; PMCID: PMC6566902
14. Bouamama S and Bouamama A. “Quercetin handles cellular oxidant/antioxidant systems and mitigates immunosenescence hallmarks in human PBMCs: an in vitro study.” bioRxiv April 16, 2022 https://doi.org/10.1101/2021.10.23.465570
15. Keenan MJ, Marco ML, Ingram DK, Martin RJ. Improving healthspan via changes in gut microbiota and fermentation. Age (Dordr). 2015 Oct;37(5):98. doi: 10.1007/s11357-015-9817-6.
16. Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 2021 Mar 9;13(3):886. doi: 10.3390/nu13030886
17. Bartosch S, Woodmansey EJ, Paterson JC, et al. Microbiological effects of consuming a synbiotic containing Bifidobacterium bifidum, Bifidobacterium lactis, and oligofructose in elderly persons, determined by real-time polymerase chain reaction and counting of viable bacteria. Clin Infect Dis. 2005 Jan 1;40(1):28-37. doi: 10.1086/426027.
18. Gill HS, Rutherfurd KJ, Cross ML, Gopal PK. Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr. 2001 Dec;74(6):833-9. doi: 10.1093/ajcn/74.6.833
19. Fu Y-R, Yi Z-J, Pei J-l, and Guan S. “Effects of Bifidobacterium bifidum on adaptive immune senescence in aging mice.” Microbiology and Immunology, Oct 2010; 54(10); 578-583 https://doi.org/10.1111/j.1348-0421.2010.00255.x
20. Wells, J.M. Immunomodulatory mechanisms of lactobacilli. Microb Cell Fact 10, S17 (2011). https://doi.org/10.1186/1475-2859-10-S1-S17
21. Pu F, Guo Y, Li M, et al. Yogurt supplemented with probiotics can protect the healthy elderly from respiratory infections: A randomized controlled open-label trial. Clin Interv Aging. 2017 Aug 8;12:1223-1231. doi: 10.2147/CIA.S141518.