Immunosenescence: The Relationship Between Immune Health and Aging

​Caitlin Beale, MS, RDN

The average lifespan has increased dramatically over the past century, thanks to advances in medicine and public health. But as we live longer, our bodies become more susceptible to disease and less able to fight infection. This is because our immune system also ages. There’s a name for this process: immunosenescence.

Immunosenescence is a natural process whereby the immune system becomes weaker with age, affecting how well you feel as you move into your older years. The good news is that immunosenescence can be slowed down with lifestyle choices, and it’s never too early to start.

This blog post explores the relationship between immune health and aging and what you can do to keep your immune system healthy as you age.

What Is Immunosenescence?
Immunosenescence is a term that refers to the age-related decline in the function of the immune system. It is a natural process that begins in early adulthood and progresses steadily as we age. 

The process of immunosenescence is complex, but overall it leads to a decrease in the number and function of immune cells.

senescent cell stops dividing and can no longer perform its normal function. These cells accumulate with age and are linked with chronic inflammation, tissue damage, and age-related health conditions because they continue to secrete inflammatory chemicals (more on inflammation and aging below).

How Do Your Immune Cells Change With Age?
Age-related declines in immune function stem from a combination of innate and adaptive immune system alterations. 
Your innate immune system responds first and provides a general immune response. The adaptive immune system kicks in later with antibodies that recognize and attack specific threats. The innate and adaptive immune systems are both needed to effectively respond to infection. 

However, since immunosenescence leads to a decline in the number and function of immune cells, older people have an increased susceptibility to illness and can also take longer to recover when they do get sick.

Immunosenescence and the Innate Immune SystemSeveral key players in your innate immune response become less responsive or don’t act as they should as you age. 

Neutrophils, for example, are white blood cells that act as first responders for your immune system. But as we get older, neutrophils aren’t able to track down and kill potential pathogens as effectively, or they respond much slower, giving potential pathogens a head start to make you sick.

The function of another type of immune cell called natural killer (NK) cells also changes with age. NK cells are primarily considered part of the innate immune system (although some research suggests that they “remember” similar to adaptive immune cells).
NK cells help clear infection, and their job is to directly kill virally infected cells. However, with age, the function of NK cells declines, and they are less able to protect against these cells.

Immunosenescence and the Adaptive Immune System
Changes to your adaptive immune system affect the cells that make antibodies to recognize and fight specific threats. As we age, the number of these cells declines, as does their ability to remember previous infections.

For example, the production of T cells, specialized cells that recognize and fight viral infections, drops with age. Over the years, T cells learn how to better fight viral infections, but we only get so many “naïve” T cells in our lifetime. So as we age, we can become more susceptible to new diseases. 

Inflammation and Aging
Age-related changes in the immune system aren’t only about the ability to fend off infection but also about chronic inflammation. The upregulation of the inflammatory immune response in the body associated with age is called inflammaging. Since many chronic diseases are linked to inflammation, this also contributes to aging and illness. 
Inflammation is a normal response of the immune system. When you’re injured or fighting an infection, immune cells release chemicals that cause inflammation. 

Signaling molecules called cytokines alert the immune system that something is amiss, turning up inflammation. The critical part of this process is that inflammation should calm down once the threat is gone.

Inflammaging occurs due to persistent inflammation when the immune system is chronically turned on. This chronic, low-grade inflammation is linked with several age-related diseases and is a significant factor in immunosenescence.

Senescent immune cells are more likely to produce inflammatory molecules, contributing to this chronic, low-grade inflammation. 
Another example concerns macrophages, the immune cells that clean up dead cells and cellular debris. According to a paper from Frontiers in Immunology,aging promotes a shift to more pro-inflammatory macrophages, furthering cytokine production and inflammation levels in the body.

Some research also links inflammation and an overproduction of inflammatory cytokines to increased frailty and mortality in older adults. 

What Influences How the Immune System Changes With Age?
Factors that influence immunosenescence include:
  • Nutrition
  • Genetics
  • Physical activity
  • Biological sex
  • Previous exposure to infections

Can You Reverse or Slow Down Immunosenescence?
You can’t slow down time, but there are some steps you can take that influence immune health and aging now at any age. The science behind immunosenescence and aging is complex. Still, lifestyle can affect how quickly your immune cells age.

Diet and InflammationThere’s a well-established connection between nutrition and immune health, leading researchers to believe nutrition may also play a role in immunosenescence.

For example, the Mediterranean diet, high in fruits, vegetables, olive oil, nuts, and fish, has been associated with a lower risk of chronic diseases. It also happens to be anti-inflammatory and could support lower inflammatory molecules and other markers of inflammation.

The Mediterranean diet also highlights fish, which contain omega-3 fatty acids. Omega-3 fatty acids may help the immune system by supporting reductions in inflammatory cytokine production. They also influence T cell proliferation and other immune cell activity.
Micronutrients and Immune SupportAging can also impact the ability to absorb certain nutrients, further contributing to immunosenescence. Older adults often eat less, have a reduced appetite, and may have difficulty preparing meals, all of which can influence nutritional status and the health of immune cells.

Micronutrients are essential nutrients that the body needs in small amounts to function properly. Many are necessary for the overall function of your immune system. Supplementing with immune-supporting nutrients like vitamins A, D, C, and zinc can help offset the impact of age-related changes on the immune system.

For example, zinc is necessary for the development and function of immune cells. It can also  help protect cells, including immune cells, from damage. 

Low zinc status influences how well the immune system functions, but supplementing with zinc supports a healthy cellular immune response.

Similar results are seen with vitamin C, which supports healthy immune cells and is shown to reduce age-related oxidative stress.
Vitamin D also plays a role in the function of immune cells. Low vitamin D levels are associated with poor immune health, but supplementing with vitamin D could improve immune function. 

Calorie Restriction and Immunosenescence
Calorie restriction may be another way to slow down the cellular aging process. Studies suggest that caloric restriction could help preserve immune function and delay the onset of age-related changes by reducing the number of inflammatory cytokines to help minimize the impact of inflammation on the body.

Caloric restriction induces autophagy, the process where old and damaged cells are removed to make way for healthy new cells. In one study, calorie restriction was found to reduce the number of senescent cells or cells that no longer function correctly. 
Since extended calorie restriction is hard for many people to sustain, intermittent fasting has become an alternative to turn on some of the same anti-inflammatory pathways. Intermittent fasting is a pattern of eating that alternates windows of eating with fasting—16 hours of fasting with 8 hours of eating is the most popular—and may prove to be a viable option to support a healthy immune response.

Physical Activity and Immune Health Support
In addition to nutrition, physical activity is another important factor in immunity and aging. Regular exercise is linked to immune health support by reducing inflammation and oxidative stress.

Exercise also helps reduce the number of senescent cells in the body. A study examining the effects of physical activity on aging found that moderate-intensity training preserved the number of naive T cells and reduced senescent T cells.

Reducing Stress Could Impact Immunosenescence
Chronic stress is another factor that can contribute to immunosenescence. When you’re stressed, your body releases stress hormones like cortisol. Chronic stress can suppress the immune system, making you more susceptible to infection and illness.

recent study from the Proceedings of the National Academy of Sciences examining adults over age 50 found that living through trauma, discrimination, and chronic stress were all linked to age-related changes in immune health via T cell function.
There are many ways to manage stress, including exercise, relaxation techniques, and spending time with loved ones. You just have to find what works best for you. Taking time to relax and destress could help reduce stress’s impact on the immune system and slow down the aging process.

Final Thoughts on Immune Health and Aging
Immunosenescence is the relationship between immune health and aging. As we age, our bodies undergo changes that can affect the function of our immune system. These changes can make us more susceptible to infection and illness.

Fortunately, there are things we can do to offset the impact of immunosenescence. Eating a healthy diet, getting regular exercise, and reducing stress could help slow down the aging process and preserve the function of your immune system. Additionally, supplementation with high-quality micronutrients could further support your immune cells.

By taking steps to preserve our immune function, we can help to protect ourselves against the effects of aging and stay healthy as we age.

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NAD+ and Sun-Exposure

You know that short-term exposure to sunlight is important for your overall health—especially those hits of the morning sun when the UV rays are lower. Sunlight also helps vitamin D production and is known to increase serotonin levels, which can help decrease depression and anxiety, and help improve sleep quality. But there are few other things to keep in mind when it comes to the sun.
So let’s talk about what an excessive amount of sun exposure can do to your cellular health, specifically in terms of UV damage and other stressors. 

What is UV damage?

First, let’s take a look at how UV rays affect our cells. There are three types of UV rays: Ultraviolet A, B, and C, also known as UVA, UVB, and UVC. 
The last two types, UVB and UVC, are mostly absorbed by the ozone layer, although UVB helps the body produce Vitamin D. That being said, the main ultraviolet radiation you’re exposed to here on earth comes from UVA. When you’re not properly protected by clothing or sunscreen, proteins and DNA are the primary targets for damage, which means your cells take the main hit and struggle to carry out their main functions, like energy production and repair. And if your cells can’t repair themselves, that’s where the aging process begins.  

What is cellular stress?

Excessive amounts of sunlight exposure stresses out your cells by depleting your NAD+, an important coenzyme in cellular energy and repair. Let’s take a look at why.  

  • Your body uses NAD+ to repair cells that become damaged as a direct result of prolonged UV exposure. 
  • A review published in the International Journal of Molecular Sciences suggests you’ll experience a greater sensitivity to sunlight if your NAD+ levels are depleted because UV rays have an adverse effect on cellular repair processes. 
  • Maintaining NAD+ levels helps support a family of enzymes called “sirtuins” that help maintain cellular health and repair cellular damage.

All in the family.

Sirtuins are a group of seven enzymes that help regulate overall cellular health like energy metabolism and stress response (e.g., what happens during UV exposure), which are all things that can affect the aging process. A review published in Trends in Cell Biology suggests sirtuins need to lean on NAD+ for help to do this job properly.
These sirtuins enzymes react to the amount of NAD+ in the cells, helping them respond to stress and maintain their overall health. Because we know that NAD+ levels decline as we age, this relationship between sirtuin activity and NAD+ effectively promotes cellular health and healthy aging. 

Protect yourself from the sun.

 If you do step out into the sun, there a few things you can do to protect yourself:

  • Cover up within 10-15 minutes of being in direct sunlight
  • Wear sunscreen with an SPF of at least 15+
  • Try to limit prolonged sun exposure.

And, if you feel like you’ve been out for too long or show signs of burning or fatigue, there are a few ways you can get back on track.  Maintaining a healthy diet, moving your body, or taking a mitochondrial supplement can all boost your NAD+ levels and help you recover more quickly. 

Nicotinamide Riboside Benefits

Often dubbed the “healthy aging” vitamin, nicotinamide riboside (NR) is a novel form of vitamin B3 that improves the way we age.  
To understand how we age, we have to look at our bodies’ underlying core processes. As we age, our bodies slow down. Our joints ache, our muscles grow weary, and the way we sleep and eat changes.  

But the true culprits of how we age lie deep within our cells. Cells are the foundation of our biology, and improving their efficiency may hold the key to answer the fundamental question, “Is there a way for us to reverse aging?”  
Nicotinamide riboside (NR) supports our mitochondria.     

No miracle pill reverses aging, but scientists began investigating a specific organelle in the cell, called the mitochondria.  
Research shows we make fewer mitochondria as we age and have attributed mitochondrial dysfunction as one of the hallmarks of aging.  

You may remember mitochondria from your high school biology class. These tiny yet powerful factories are responsible for producing 90% of your cell’s energy. Without our mitochondria, we would not exist as the complex organisms we are today.  

Vitamin B3 is a necessary nutrient that supports normal mitochondria function. Although there are other variants of vitamin B3, nicotinamide riboside is the most efficient form, like premium-grade fuel at a gas pump.   
Nicotinamide riboside (NR) boosts NAD+ effectively.  

A significant reason why nicotinamide riboside is closely associated with aging research is because of the vitamin’s unique ability to increase NAD+ efficiently.  

NAD+ is required for specific enzymes in your mitochondria, playing a direct role in your cell’s energy creation.  
Unfortunately, there is evidence to suggest that age has a direct correlation to our NAD+ levels. Research from the University of New South Wales uncovered NAD+ levels decline by over 50% between the ages of 40 and 60, and low levels of NAD+ are linked to mitochondrial inefficiency.  

Thankfully, a review paper published in the Translational Medicine of Aging shows the positive potential of boosting NAD+. The review states,  

“NAD+ replenishment may serve as a potential therapeutic strategy for aging and  multiple conditions to improve the quality of life of the increasing aged population.”  
Why don’t we take more NAD+?  

Unfortunately, it’s not so simple. NAD+ is very difficult to maintain in capsule form, and there are questions around its potency as a supplement. The molecule quickly degrades when exposed to light and heat and deteriorates when exposed to water.  

Even if it were to maintain its pill form, your body doesn’t appear to take NAD+ as readily. A paper in the Journal of Nutritional Science and Vitaminology shows that our digestive process breaks down orally-administered NAD+ into common NAD+ precursors before the cells get a chance to absorb it.  

To simplify the process for our bodies, researchers have examined NAD+ precursors instead. NAD+ precursors already exist in the staple diet today as vitamin B3.  

However, most of the available vitamin B3 comes in the form of niacin. Niacin has been around for some time, but its unsightly symptom of skin flushing challenged researchers to look elsewhere.  

Nicotinamide riboside is favored because it’s absent of these skin flushing effects, but it also raises NAD+ more efficiently than other vitamin B3s.  
Nicotinamide riboside (NR) fights the effects of damaging free radicals.  

Your mitochondria aren’t perfect mechanisms. During their energy-making process, mitochondria produce byproducts–free radicals.  

Free radicals can wreak havoc on your cells, damaging essential cell functions.  

In standard settings, your body naturally produces enough antioxidants to combat these free radicals. However, certain situations of metabolic stress can tip the scales.  

Lifestyle behaviors such as poor diet, drinking, ​sedentary behavior, sleep deprivation, and long-term sun exposure can all lead to an imbalance between your free radicals and antioxidants.  

How does this happen? Your body requires significant energy resources to combat and recover from these activities, so your mitochondria kick into overdrive to provide the energy and offset the sudden demand.  
By boosting NAD+, nicotinamide riboside can help limit free radical damage.  
Nicotinamide riboside (NR) promotes cell repair.  

Nicotinamide riboside activates sirtuin activity in the cell. Sirtuins are a class of enzymes in the body responsible for gene regulation, the systemic process of turning certain parts of your genetic code on and off.   

Why is this system important? Turning off specific genes, aka “silencing,” is critical to regulating the cell, maintaining its shape and health for optimal function.   

But sirtuins play a critical role in cell repair as well. A review published in the Current Opinion in Genetics & Development states, 
“In the past decade, the roles of sirtuins in maintaining genomic stability have been described, as regulators of DNA repair pathways, chromatin structure, and telomere maintenance.” 

Like the mitochondrial enzymes, sirtuins cannot operate without the help of the coenzyme NAD+. And nicotinamide riboside helps boost NAD+, activating cell repair in effect.  
Nicotinamide riboside (NR) supports heart health.  

Your heart is one of the most critical organs in your body, requiring loads of energy to sustain your heartbeat.
Being one of the most energy-expensive functions in the body, thousands of mitochondria churn out energy in your heart cells.    
However, your heart’s physiology can change with age. Your valves can become stiff, your heart walls can grow thick, and your heart’s mitochondria can become less efficient.  

A review from Circulation Research shows that your mitochondrial count in cardiac cells declines as you age. Fewer mitochondria leave less help to divide the work—the labor of generating energy for your heart cells.  

In combination with a healthy diet and exercise lifestyle, nicotinamide riboside supports your heart health by supporting your mitochondria.   
Nicotinamide riboside (NR) helps support healthy muscles.  

When you think about how nicotinamide riboside fuels your body’s cellular energy, the first thing you might wonder is how it affects your workout.  

Like the heart, your muscle cells require thousands of mitochondria because of their unique energy demand. And where there are mitochondria, there needs to be an abundant amount of NAD+.   

A review published in Skeletal Muscle notes the need for NAD+ in muscle development. The abstract states,  

“The vast majority of studies indicate that lower NAD+ levels are deleterious for muscle health and higher NAD+ levels augment muscle health.”  

But muscle function isn’t all about energy and its expense. Every workout needs a recovery period, and with it comes sore muscles and a bag of ice. How does NAD+ play a role post-exercise?  

According to a review published in the International Journal of Molecular Sciences, the NAD-dependent enzymes, sirtuins, play a critical role in muscle repair. In response to exercise, sirtuins activate two functions that enable the body to be more readily prepared for your next workout: (1) mitochondrial biogenesis and (2) oxidative capacity. 
  • (1) Mitochondrial biogenesis is a process where the body creates more mitochondria. With more mitochondria, the body is more readily capable of supporting the increase in energy demand that comes with exercise.   
  • (2) Oxidative capacity is a measure of a muscle’s maximal capacity to use oxygen. With higher oxidative capacity, the muscle can exert greater efficiency. 

Nicotinamide riboside is the most efficient way to boost NAD+, best serving these NAD-dependent mechanisms in muscle cells.  
Nicotinamide riboside (NR) promotes healthy aging.  

“Anti-aging” is a marketing gimmick. There are no products out there that can effectively reverse the aging process. Instead, the World Health Organization (WHO) is focused on promoting the idea of healthy aging. 
The WHO defines healthy aging as “the process of developing and maintaining the functional ability that enables wellbeing in older age.”   

Healthy aging is about maximizing your lifetime to its fullest potential, retaining your independence and mobility.   

Nicotinamide riboside is classified as a healthy aging supplement because of its unique ability to support health on a cellular level at any age. By targeting the maintenance of cells, NR helps your cells sustain their resilience to aging.   

Although being called the “anti-aging” pill is more of a misnomer, nicotinamide riboside’s unique role in countering everyday wear and tear directly contributes to anyone’s desire to age gracefully.   
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