The key isn’t chronological age, but immune age — and you can turn back that clock
The average life expectancy is 73 years for a man and 79 years for a woman in America today. While overall life expectancy has declined in the past few years, the number of those over age 85 has increased. The U.S. Census Bureau reports 5.7 million Americans are between the ages of 85 and 94; approximately 631,000 are over age 95. The number of centenarians has risen to an all-time high of nearly 90,000, nearly twice as many as there were in 2004.1
Many of these oldest Americans are in good physical and cognitive health and continue to live active, independent lives. The centenarians have achieved a life span that is 20 years longer than the average American’s, while also achieving a long health span — the length of time when they’re not just alive, but healthy. These aged individuals have postponed the most common causes of death, such as heart disease and cancer, until their 80s or even 90s, while experiencing poor physical and cognitive health only for a compressed period near the end of life.2
How do they do it? A big part of their long life span comes from an immune system that remains robust and resilient as they age. What we can learn from the eldest doesn’t guarantee you’ll become a centenarian, but a more robust immune system may help you achieve a longer health span.
Aging and immunity
As we age, proper immune function tends to decline.
Immunosenescence generally begins around age 60, weakening immunity and increasing the risk of autoimmune disease, cancer and severe illness from infectious diseases, such as influenza and COVID-19. The neutrophils of the innate immune system begin to slow down and malfunction, making the immediate response to an invader slower and less efficient. Faulty neutrophils are an underlying cause of “inflammaging,” the low-level chronic inflammation common in older adults. The T and B cells of the adaptive immune system also slow down, taking longer to mount an antibody defense and sometimes “forgetting” how to respond to an invader they have seen before.
Your chronological age and your immunological age aren’t the same. For some, the immune system ages faster. Others, including the advanced aged, have immune systems that are more resilient and continue to provide effective protection as they age. Centenarians possess a unique immune cell composition and activity, giving them a highly functional immune system. This allows them to live longer and display high levels of immune resilience, which empowers them to withstand or bounce back from infections and inflammatory stressors that could otherwise lead to autoimmune disease.
Recent research using advanced laboratory techniques to assess the relative proportions of CD8+ and CD4+ Tcell levels suggests a lower ratio of CD8 cells to CD4 cells confers the most immune resilience. People who are the most immune resilient can restore this ratio of T cell types after recovering from an illness or other inflammation-inducing stressor.3 Advanced cell sequencing techniques have also shown the oldest cells have an unusually high percentage of cytotoxic CD4 T cells, also known as killer T cells. These cells can recognize antigens, directly kill pathogens and destroy mutated or cancerous cells. Killer T cells are scarce in the immune system, making up only about 2.8% of all helper T cells in most people. In the eldest people, however, they make up about 2% of all T cells. The presence of so many killer T cells helps explain why the eldest are able to avoid infectious disease, autoimmune disease and cancer — their immune system has a heightened ability to destroy pathogenic or defective cells before they can do real damage.4
What’s your immune age?
Those most advanced in age were fortunate to inherit “elite” immunity genes that continue to provide ongoing immune resilience, giving them immune systems resistant to age-related decline. However, most adults experience a decrease in immunity with age, leaving them far more vulnerable to disease. After about age 50, the immune system starts to clog up with senescent cells, cells no longer fully functional but that haven’t been destroyed by the body’s usual process of autophagy. The result is immunosenescence (an accumulation of inefficient adaptive immunity cells) and inflammaging, low-level chronic inflammation caused by the secretion of pro-inflammatory cytokines by the senescent cells.5
Immunosenescence isn’t solely an age-dependent process. Chronic disease and poor lifestyle choices, such as smoking, can accelerate it. This means your immune system may be functionally older than your chronological age. Bringing your immune system closer to your age is a vital first step toward increasing your health span and possibly your life span.
Biomarkers for longevity
Based on biomarkers common to older people who continue to be physically and cognitively healthy into their 80s and beyond, we can look at those of younger people and see areas where changes might lead to a greater health span and possibly a longer life span. Some biomarkers, such as blood pressure, body composition and maximum grip strength, are easy to assess. Others, such as VO2 max (a cardiovascular fitness measurement), require specialized equipment. Bloodwork to look at possible longevity biomarkers includes testing for immune-regulating interleukins, including IL-1β, IL-6 and IL-8, and other immunity markers, such as TNF-α, C-reactive protein, hemoglobin A1C and APOE4 (a marker of Alzheimer’s disease risk). Testing for zonulin and occludin, two markers of tight junctions in the gut wall, and LPS (lipopolysaccharides), is also recommended. These markers are important indicators of the health of the gut/immune axis.
Turning back the immunological clock
When tests reveal an immunological age beyond your chronological age, removing senescent cells from the immune system can help turn back the immunological clock. Rejuvenating immune cells reduces inflammaging and supports the immune system in functioning more efficiently, and returning quickly to a balanced level after fighting off an illness. In other words, it’s possible to help your immune system function at a level closer to or even below your chronological age.
Rejuvenating the immune system means flipping the metabolic switches on three aging pathways, including Sirtuins, AMPK and mTOR.
Sirtuins
Sirtuins are a family of cellular enzymes that are essential in managing many aging-related cellular processes. Sirtuins slow cellular senescence by repairing DNA damage, including damage from oxidative stress, and help maintain the integrity of chromosomes by delaying telomere shortening. In addition, these enzymes regulate the function and creation of new mitochondria within the cell. Your production of sirtuin declines over time, leading to an increased risk of cancer and other chronic diseases and a decrease in cellular energy production.6
The AMPK pathway
The adenosine monophosphate (AMP)-activated protein kinase (AMPK) metabolic pathway is vital to maintaining a strong immune system. This pathway activates autophagy (literally, “self-eating”), the process of breaking down senescent cells and recycling their proteins into new ones. As part of recycling, autophagy also removes cellular debris, such as damaged proteins, that congest the cells.
The AMPK pathway is also crucial for energy production in the mitochondria. When activated, the pathway triggers changes signaling your cells to make more mitochondria and improve insulin sensitivity. Under the influence of AMPK, your cells become more fuel-efficient and stress-resistant.
The mTOR pathway
The kinase mechanistic target of rapamycin (mTOR) pathway senses the presence of growth factors and amino acids in your body. The mTOR pathway is activated when these are abundant because caloric intake is high. Your cells go into anabolic mode and start to grow and divide. This is desirable when growth or healing is needed, but constant activation of the pathway can decrease longevity and lead to neurodegenerative diseases, diabetes, obesity, depression and certain cancers. The mTOR pathway is overactive for many people in the modern food-rich environment because it constantly senses an overabundance of nutrients.
The AMPK pathway is suppressed when the mTOR pathway is highly active. When mTOR is unopposed by AMPK, the anabolic pathway stays stuck in the “on” position. The anabolic state from continuous mTOR activation makes autophagy inefficient and allows the accumulation of zombie cells in the immune system and the rest of the body.
Shutting off mTOR production means shutting down anabolism, the process that is essential for cell maintenance and growth. However, reducing mTOR production to keep it from being constantly in the activated state helps balance AMPK production and can reduce immunosenescence and inflammaging.
Flipping the metabolic switches for better immunity
Sirtuins, mTOR and AMPK are all highly responsive to both exercise and caloric restriction. The effects are felt throughout the body but are particularly profound in the aging immune system.7
Exercise
The loss of skeletal muscle mass, or sarcopenia, is a hallmark of aging that affects not only body composition and the risk of frailty, but also the immune system. By age 65, many people have lost 25%of their muscle mass. The less skeletal muscle an older adult has, the more likely they will experience immunosenescence, particularly in reduced macrophage and T cell function.8
Regular exercise (four times a week or more) that includes both resistance and aerobic training is critical to avoiding or minimizing sarcopenia while maintaining strong immunity.9 Said activity seems to slow immunosenescence in the immune system’s innate and adaptive branches. Exercise also improves natural killer cell function, T cell production and the activity of neutrophils.10
Sirtuin production is stimulated by physical exertion, helping normalize age-related mitochondrial dysfunction.11 Exercise is also a potent activator of the AMPK pathway and its effects on immunity. For example, activating the pathway is crucial for the optimal expansion of helper T cells when fighting infection.12
Eating for immunity
Time-restricted eating (TRE) is a valuable tool for rejuvenating the immune system and possibly increasing both life span and health span. In a food-rich environment, the mTOR pathway is highly active. Cell proliferation (and possibly cancer) is encouraged when this happens, while autophagy to repair and remove defective cells is inhibited. Time-restricted eating, or at least caloric restriction, slows the mTOR pathway and supports the AMPK metabolic pathway. When the AMPK pathway is activated, it induces longevity factors by activating sirtuins, reducing chronic inflammation, creating new mitochondria and improving immunity.13 Fasting also deletes old and defective white blood cells and stimulates the generation of new ones.
Several dietary changes support the immune system and may extend health span and life span. In general, an anti-inflammatory diet high in fruits and vegetables and low in carbohydrates and processed foods is helpful. Also, avoid foods that contain gluten, added sugar, dairy and alcohol.
The broad range of immune-boosting phytochemicals found in Himalayan Tartary buckwheat (HTB) make this superfood an excellent addition to a healthy diet. Flour from HTB contains more than 100 immune-active nutrients, including magnesium, zinc, B vitamins, rutin, quercetin and Hobamine (2-hydroxybenzylamine or 2-HOBA), a phytonutrient that provides positive support for a robust immune system. Despite the name, Himalayan Tartary buckwheat contains no gluten; it’s a good source of soluble fiber, prebiotics and other nutrients that support gut health.
Maintaining good gut health is an essential aspect of maintaining good immunity. A healthy gut microbiome is a common characteristic of the oldest old; many have a gut microbiome composition that resembles that of a much younger person.14 To keep your gut microbiome in sync with your immune system, eat a healthy, high-fiber diet and avoid sugary or processed foods.
Final thoughts
As doctors of chiropractic, we have long understood the critical role of the immune system in maintaining health and warding off disease. However, recent advancements in immunology have revealed the profound impact of immune rejuvenation on extending not just life span, but also health span. The immune system, our body’s natural defense mechanism, often falters with age, leaving us vulnerable to a myriad of health issues. Yet, the emerging field of immune reboot promises a revolutionary paradigm shift, enabling us not to merely delay the aging process but actively reverse it. Through tailored interventions that rejuvenate the immune system, we can empower our patients to not only live longer and healthier lives, but to enjoy vibrant and fulfilling lives.15
ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 best-seller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named Silverman “Sports Chiropractor of the Year” in 2015. Silverman is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on both the speaking circuits and the media. He is a thought leader in his field and practice, and a frequently published author in peer-reviewed journals and other mainstream publications. Silverman was the principal investigator on two Level 1 laser FDA studies.
His new book, Amazon’s best-seller, “Immune Reboot,” was released in December 2022. Reach him via social media through the links on his website, drrobertsilverman.com.
References
- U.S. Census Bureau. The Older Population: 2020. Report Number C2020BR-07. May 25, 2023. https://www.census.gov/library/publications/2023/decennial/c2020br-07.html. Accessed Nov. 12, 2023.
- Andersen SL, et.al. Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. J Gerontol A Biol Sci Med Sci. 2012;67(4):395-405. PubMed website. https://pubmed.ncbi.nlm.nih.gov/22219514/. Accessed Nov. 12, 2023.
- Ahuja SK, et. al. Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection. Nat Commun. 14,3286(2023). https://doi.org/10.1038/s41467-023-38238-6. Accessed Nov. 12, 2023.
- Hashimoto K, et. al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians. Proc Natl Acad Sci USA. 2019;116(48):24242-24251. PubMed website. https://pubmed.ncbi.nlm.nih.gov/31719197/. Accessed Nov. 12, 2023.
- Pietrobon AJ, et. al. Immunosenescence and Inflammaging: Risk Factors of Severe COVID-19 in Older People. Front Immunol. 2020;11:579220. PubMed website. https://pubmed.ncbi.nlm.nih.gov/33193377/. Accessed Nov. 12, 2023.
- Lee SH, et. al. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019;52(1):24-34. PubMed website. https://pubmed.ncbi.nlm.nih.gov/30526767/. Accessed Nov. 12, 2023.
- Weyh C, et. al. Physical Activity and Diet Shape the Immune System during Aging. Nutrients. 2020;12(3):622. PubMed website. https://pubmed.ncbi.nlm.nih.gov/32121049/. Accessed Nov. 12, 2023.
- Nelke C, et. al. Skeletal muscle as potential central link between sarcopenia and immune senescence. EBioMedicine. 2019;49:381-388. PubMed website. https://pubmed.ncbi.nlm.nih.gov/31662290/. Accessed Nov. 12, 2023.
- Beaudart C, et. al. Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review. Osteoporos Int. 2017;28(6):1817-1833. PubMed website. https://pubmed.ncbi.nlm.nih.gov/28251287/. Accessed Nov. 12, 2023.
- Weyh C, et. al. Physical Activity and Diet Shape the Immune System during Aging. Nutrients. 2020;12(3):622. PubMed website. https://pubmed.ncbi.nlm.nih.gov/32121049/. Accessed Nov. 12, 2023.
- Vargas-Ortiz K, et. al. Exercise and Sirtuins: A Way to Mitochondrial Health in Skeletal Muscle. Int J Mol Sci. 2019;20(11):2717. PubMed website. https://pubmed.ncbi.nlm.nih.gov/31163574/. Accessed Nov. 12, 2023.
- Mayer KA, et. al. The energy sensor AMPK orchestrates metabolic and translational adaptation in expanding T helper cells. FASEB J. 2021;35(4):e21217. PubMed website. https://pubmed.ncbi.nlm.nih.gov/33715236/. Accessed Nov. 12, 2023.
- Moskalev A, et. al. Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience. Aging Dis. 2020;11(6):1363-1373. PubMed website. https://pubmed.ncbi.nlm.nih.gov/33269094/. Accessed Nov. 12, 2023.
- Pang S, et, al. Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures. Nat Aging. 2023;3(4):436-449. PubMed website. https://pubmed.ncbi.nlm.nih.gov/37117794/. Accessed Nov. 12, 2023.
- Silverman R. Immune Reboot. 2022: Westchester Integrative Health, N.Y. https://drrobertsilverman.com/inside-out-health/. Accessed Nov. 12, 2023.
