What Is Immunosenescence? Understanding How Your Immune System Changes

What really drives aging? It’s a question worth asking and is one that age researchers called geroscientists explore, helping to provide a framework about what happens during the aging process and importantly—what we can do about it. It turns out that immune health is the scaffolding that holds much of that aging framework together.

Key Takeaways

Immune aging is a normal part of life.
Healthy lifestyle choices can help support immune function at any age.
Small, consistent habits can contribute to healthy aging over time.

Key Terms

Geroscience: the scientific field that studies how the biological processes of aging influence health.
Senescent: describes a cell that has stopped dividing but remains biologically active. These cells can disrupt healthy cellular communication and contribute to inflammation and age-related changes in tissue function.
Antigens: substances or molecules that the immune system recognizes as specific targets.
Neutrophils: immune cells that rapidly respond to threats and help protect the body as part of its first line of defense.
Healthspan: the number of years a person lives in good health and maintains physical and mental function.

The Aging Immune System: What You Need to Know

Geroscience research points to a person’s immune age as a differentiator in the aging process. To provide a sense of how this works, research looking at 135 people for 9 years discovered that the human immune systems mostly follow a predictable trajectory over the course of a lifetime.¹ Where you are in the trajectory seems to reflect your immune age, which doesn’t reflect how many years you’ve been alive, but instead reflects the age of your cells, tissues and organs. Testing that utilizes such tools as wearable devices or blood chemistry results help reveal this age.

Variations in immune age are the result of differences between people, such as exposure to bacteria and viruses, daily habits or genetic uniqueness. New research even suggests that parts of the immune system can burn out, resulting in something called immune exhaustion.²

One major factor that can cause a person’s immune age to be older is his or her rate of immunosenescence, which is one of the major biological processes underlying immune aging.

What is Immunosenescence?

Immunosenescence, a term coined by late pathologist Roy Walford in the 1960s, refers to the “progressive remodeling and decline of immune function with aging”.³ Inevitably, the immune system changes we age; it’s simply unavoidable. But this decline involves specific alterations to both the innate and adaptive immune systems, where these remodels cause immune function to work less efficiently over time.

How Does the Immune System Change with Age?

“Innate” and “adaptive” represent the two arms of the broader immune system. The innate system provides our first line of defense and is nearly intact when we are born. It operates using pathogen-killing cells such as neutrophils and macrophages, which provide early responders to an invasion within the body.

The adaptive, or acquired, system is slower, but uses a targeted approach where T-cells, B-cells and antibodies to respond to specific antigens. As the name suggests, it learns from what the body goes through, providing a type of immune memory, which can activate when memory B-cells recognize a pathogen’s re-entry, potentially preventing the same illness from happening twice.

Immunosenescence impacts both arms of immune function, taxing the way these two arms normally work and contributing to the dimming of some crucial abilities over time. Hallmark features of this decline include the following:

Inflammaging (inflammation + aging): a lingering level of low-grade inflammation
The accumulation of senescent cells
Thymic involution: reduced output of T cells
Loss of ability to respond to antigens⁴

Immunosenescence vs. Inflammaging: What’s the Difference?

Inflammaging and Senescent Cells

Inflammaging (pronounced in-FLA-muh-jing), was initially defined in 2000 and “refers to chronic, low-grade, systemic inflammation that increases with age”; it’s not driven by overt disease but many factors that result in altered immune regulation.⁵ While this may sound similar to immunosenescence, each functionally undermines immune resilience differently – with inflammaging contributing to tissue damage and immunosenescence reducing the ability to respond effectively to challenges.

While inflammation initially has a protective effect in the body that serves to help repair tissue and activate immune function, “inflammaging arises from the chronic activation of immune cells”⁶ related to secretions released by senescent cells that have not been properly cleared. Senescent cells have stopped dividing but are still alive and metabolically active.

Normally, immune cells can recognize and remove senescent cells, but when immune-mediated clearance becomes less efficient, senescent cells may continue releasing factors including inflammatory cytokines, chemokines and proteases that contribute to low-grade inflammation.

A good example of this are neutrophils, innate immune cells whose normal life cycle includes performing their function, apoptosis (programmed cell death) and then clearance. Immune aging extends the lifespan of neutrophils. This extended time in the body allows them to create and exacerbate inflammatory conditions by releasing cytokines.⁴ They can also suppress the function of other immune cells, particularly T cells.

The feedback between immunosenescence and inflammaging can further contribute to age-related immune dysfunction and may reduce a person’s resilience.

Signaling Pathways

Dysregulation of crucial signaling pathways is another cycle that plays a role in accelerated immunosenescence since pathways like NF-κB, mTOR, AMPK, melatonin and sirtuin (among others) form a “regulatory network to modulate immunosenescence”.⁴ Signaling pathways are chains of chemical reactions where molecules inside a cell work together to control specific functions like cell growth, division, or death.

Alteration of these pathways leads to impaired immune responses and increased susceptibility to age-related health conditions, which means supporting them is crucial. They can either be upregulated or downregulated at inopportune times causing the immune system to either respond too strongly or not strongly enough when a modulated path is needed.

Imagine a set of traffic controllers set free in the body with little sense of order or consistency and it becomes easier to see how these misdirected responses and confusion can contribute to immunosenescence.

Thymic Involution

Even in the wellness world, the thymus gland doesn’t get a lot of airtime and perhaps this is because its fade-out seems inevitable. The thymus lives beneath the breastbone above the heart and is a vital part of the adaptive immune system where white blood cells from the bone marrow eventually mature into functional T cells. While active in childhood, it gradually shrinks with age, about 3 percent a year from the onset of puberty.⁷ As time goes on the thymus shrinks until there is very little left. This shrinking with age is known as thymus involution.

Because it’s part of the adaptive immune system, the challenge comes when older people with little thymus left face any kind of invader this system has not dealt with before. The consequence is that this system can face an enormous task it’s unprepared for.

In case your first question is How can I support my thymus?, thymic regeneration is actively being researched. One study of 125 amateur cyclists ages 55 to 79 found that found that T-cell counts were so similar to those of much younger people that the thymus itself was youthful.⁸ Even though this was an active cohort that had been cycling for decades, it speaks to the power of staying active.

Why Does Immunosenescence Matter?

Understanding the driving factors behind immune age and the changes that can happen during immunosenescence can fill in a map you can take to help protect immune organs, cells, and signaling pathways. The earlier the better. Immunosenescence is not something to address when you’re rounding the corner to 60 or start to face a health issue. Make time in your calendar for next week. Immune decline can start earlier than you’d think and can be accelerated by various lifestyle factors, such as smoking, poor dietary habits and being sedentary. Something that might be helpful is considering your “intrinsic capacity,” a concept the World Health Organization defines as “The composite of all the physical and mental capacities of an individual”⁹ and is a way of looking at what your body and mind are capable of still doing, rather than focusing on what they can’t.

For that framework, it’s not necessary to know your immune age. You can simply begin taking steps to keep it low (at any age!) and look for what habits will help prevent or slow immunosenescence.

How Can You Support Healthy Immune System Aging?

Habits and Nutrients That Support Normal Immune Function

One major game changer is exercise – surprise! In one study, researchers measured exercise levels and neutrophil migration in 211 older adults, showing that those taking an average of 10,000 steps per day had younger neutrophils.¹⁰ Exercise has other immune-boosting effects as well as myriad other benefits.

Another key step is making what you eat count. Consuming whole foods naturally packed with vitamins and minerals provides critical co-factors for your body’s foundational functions, and that means access to the essential nutrients when they’re needed. Key nutrients are vitamins C and D and zinc and selenium because of their critical and complementary roles in daily immune function.

A lot of these same whole foods (think fruits, vegetable, nuts and seeds) are sources of other great things that support a robust immune system, such as plant polyphenols for a steady supply of antioxidant protection, as well as dietary fiber that both keeps a lean metabolism and feeds gut microbes. Healthy microbes help keep the body in stasis by producing metabolites needed for immune function. Poor gut health is a driver of a lower immune age, particularly since the gut is in communication with all of the body’s others structures and organs.

Good sleep hygiene also helps keep the immune system robust as we age. Research shows how sleep and immune health are deeply intertwined as “adequate sleep promotes intense immune responses and thus enables efficient pathogen clearance and the maintenance of immune memory.”¹¹ It also helps to regulate inflammation. Additionally, a good night’s rest helps with stress resilience when we’re awake. While it’s well known how detrimental the effects of stress can feel, research regularly connects stress to an undermined immune system.

One last step to consider is reducing energy intake, which has been studied to potentially extend both lifespan and healthspan. This can mean a reduction in macronutrients like calories or fat, but it can also mean the time at which one is consuming calories in the day, sometimes called intermittent fasting. The body is satiated when nutrient-dense foods are consumed. Prioritizing those types of foods or even slowing down and giving fiber a chance to make you feel full, can help quell latent hunger noise.

Conclusion

While many of us likely have a story of aging in our head, that story can make it all too easy to accept the belief that certain changes in the body are inevitable. The goal to keep front of mind is a long healthspan, which is innately connected to healthy immune function in all its myriad functions. The immune system is massive, comprised of hundreds of cell types and signaling molecules, endlessly interacting. Only the brain is more complex.

That complexity doesn’t require sophisticated or expensive solutions. While novel therapies targeting immune cells against senescence in elderly individuals exist, there are also numerous ways to care for and nourish this intricate system – and most of them come down to practical, day-to-day habits that just need to be tried out. It might be helpful to talk about solutions with a friend or a group, which can provide the community connection we need while offering the support needed to sustain making a positive change for health. Whatever you do to maintain healthy immune function, remember your chronological age is just a number.

FAQs

At what age does immunosenescence begin?
There isn't a single age at which immunosenescence suddenly begins. It's a gradual, lifelong process, and different parts of the immune system age at different rates. At least one aspect of it, thymic involution, begins around puberty. Since some research points to an active lifestyle helping to keep the thymus young and producing youthful amounts of Tcells, starting a habit and making it a lifelong routine can provide support.
What are the signs of an aging immune system?
Immune aging occurs largely at the cellular level, so it does not have a single set of outward “signs.” Scientists characterize immunosenescence by changes such as reduced thymic activity, fewer naïve T cells, changes in T- and B-cell function, altered immune signaling and greater levels of low-grade inflammatory activity. Together, these changes can affect how efficiently the immune system responds and adapts to challenges. Maintaining healthy lifestyle habits and adequate intake of essential nutrients can help support normal immune function and immune resilience as you age.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

Julie Larson, Senior Regulatory Specialist

Julie is a writer, researcher, and educator with an MFA in English and is also a certified meditation instructor. She is deeply invested in understanding what helps the human body function optimally. Her goal is to empower others on their health journey by helping them make informed choices based on sound research shared in a relatable and engaging way. She believes that supporting the health of our bodies not only allows us to feel better mentally and physically but also helps to fuel what we really want to accomplish.

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