Rethinking Inflammation, Part 2: What is Inflammaging?

In Part 1 of our Rethinking Inflammation series, we explored a different way of thinking about inflammation.  Rather than viewing inflammation as something the body needs to shut down, researchers now understand that the body has an active process for bringing inflammation to a close, called resolution. 

Specialized pro-resolving mediators (SPMs) are important signals in this process, helping coordinate the transition from an inflammatory response toward clean-up, repair, and a return to balance.  But what happens if that process becomes less efficient, or less precise? 

As we age, changes in the immune system and inflammation-resolution pathways can make it harder for the body to resolve inflammatory responses fully.  Over time, this can contribute to a persistent, low-grade, unresolved inflammatory state that medical researchers refer to as inflammaging.¹ 

Living with this chronic inflammation can lead to various health issues and significantly impact quality of life.  Here in Part 2, we dive into the topic of inflammaging — what causes it, what it means for your health, and nutrients that help support the body’s defense systems. 

Why Inflammaging Matters to You 

You don’t have to be “old” to care about inflammaging.  You just have to be aging.  And inflammaging may be coming along for the ride.  Inflammaging is the underlying “foundation” of (and strongly associated with) many of the chronic conditions that become more common with age, including:² 

• Neurodegenerative diseases, including Alzheimer's and Parkinson's disease 
• Cardiovascular disease, including atherosclerosis and stroke 
• Metabolic disease, including insulin resistance, type 2 diabetes, and fatty liver disease 
• Arthritis, including osteoarthritis and rheumatoid arthritis 
• Cancer, including colorectal, breast, prostate, and the many other cancers 

Inflammaging has also been implicated in conditions such as chronic kidney disease (CKD), chronic lung disease, and more. 

These relationships are complex.  Inflammaging isn't the sole cause of these diseases, and chronic inflammation can be two-directional:  both contributing to and resulting from many of them.  These connections illustrate why maintaining a healthy balance between inflammation and resolution may matter for more than just recovery from an occasional injury.  At its core, healthy aging isn't about avoiding every source of stress or inflammation; rather, it's about maintaining the ability to respond, recover, repair, and return to normal function. 

Are You Feeling Inflammaging Now?  What Inflammaging Can Look Like 

Take a moment and think about how your body’s been responding to everyday challenges lately. 

• Does it take longer to recover after a workout or physical exertion than it used to? 
• Do you experience more frequent aches, stiffness, or joint discomfort? 
• Do minor cuts, scrapes, or other injuries seem to take longer to heal? 
• Do you feel less energetic than you once did? 
• Is it harder to maintain the same muscle strength or physical capacity? 
• Does your body seem less able to “bounce back” after an illness, travel, or a few nights of poor sleep? 

These experiences can have many causes, and none of them by themselves means you have inflammaging.  But they highlight an important concept: resilience depends in part on how effectively the body responds to and recovers from stress.  In fact, if inflammaging has an opposite, resilience would be it.  That is, if you’re holding inflammaging at bay, you’re maintaining your resilience. 

Inflammaging vs Acute Inflammation 

Technically, inflammaging refers to a chronic, low-grade inflammatory state associated with aging.³  It’s as if the body is unable to fully resolve inflammatory episodes, and they linger seemingly indefinitely.  Also, inflammaging doesn't necessarily have an obvious trigger, unlike acute inflammation. 

Acute inflammation has a clear reason for starting in response to a specific threat or injury.  A virus enters the body.  Bacteria cause an infection.  You cut yourself or experience another form of tissue injury or trauma.  The immune system recognizes the threat and launches a coordinated response.  Ideally, once the threat has been addressed, that response resolves. 

Inflammaging is different.  Instead of inflammation rising in response to one specific event and then returning to baseline, inflammatory signaling can remain elevated for long periods.  Think of it as a slow, silent build-up of inflammatory activity — small amounts of inflammatory signaling may persist or recur without being completely resolved. 

What Causes Inflammaging? 

There isn't one single cause of inflammaging.  Instead, inflammaging can be driven when the body’s inflammatory response gets “switched on” continually and repeatedly over a person’s lifetime, while at the same time the body’s natural SPM resolution system (the “off switch”) becomes less efficient.  This makes it more difficult to maintain a healthy inflammatory balance.  For example, aging can be associated with these drivers of inflammaging:⁴  

• Aging immune cells:  Changes in immune-cell function, which can make inflammatory responses less precise or more persistent. 
• Leftovers building up:  Accumulated cellular and metabolic changes, including the build-up of damaged cells and cellular debris; this includes “zombie” cells (senescent cells) that stop doing their normal job but don’t die and lurk around, often releasing inflammatory signals. 
• Gut dysfunction:  Changes in the gut and its microbial environment, as well as a “leaky” gut (a more permeable gut barrier), which can influence immune activity. 
• Metabolic stresses:  Obesity, insulin resistance, and metabolic syndrome. 
• Lifestyle:  Long-term exposure to inflammatory stressors, including poor diet, physical inactivity, chronic stress, inadequate sleep, smoking, and other environmental factors. 

Whether you’re 35 or 85, these processes are likely underway to lesser or greater extent in your body.  On top of that, these factors can interact with each other, and aging can affect both how your inflammatory response is activated and how effectively it is resolved. 

How Aging Can Affect Resolution 

As we discussed in Part 1, inflammation resolution is an active biological process, and SPMs are crucial molecular signals that help coordinate the transition from inflammation toward resolution.  Think of SPMs as the signals that tell the immune system when the “fire” of inflammation has been contained and it’s time to shift from “firefighting” to clean-up and repair.  

Growing research suggests that aging can affect both the body's ability to produce certain SPMs and its ability to efficiently respond to pro-resolving signals.⁵   Several changes may contribute, such as:⁶  

• Aging may alter or reduce the production of certain SPMs. 
• The activity of enzymes involved in SPM production can change, also reducing SPMs. 
• Cells may respond differently to SPMs because of changes in receptors and signaling pathways. 
• Immune cells involved in resolution may function less efficiently. 

No single number describes how much SPM production declines with age.  Research has found changes in specific SPMs and resolution pathways rather than a universal percentage decrease across the body. 

The takeaway is that aging may make it harder for the body to resolve inflammatory responses fully.  If inflammation is an essential part of the body's defense system, the goal isn't to eliminate it.  Instead, it's to support the body's ability to respond appropriately and resolve the response when the job is done. 

Healthy lifestyle habits such as regular physical activity, a nutrient-dense diet, adequate sleep, stress management, not smoking, and limiting alcohol can support overall health and healthy inflammation resolution.  We’ll get into these strategies in a future article.  Though, below we’ll summarize one direct nutritional connection to the resolution process we covered in Part 1, which is omega-3 fatty acids and SPMs. 

Omega-3s, SPMs, and Healthy Aging 

When it comes to omega-3 fatty acids, there is a long list of benefits, from sharper cognition and a healthier heart to better vision and beyond.  But a lesser-known benefit isn’t tied to a specific organ.  Omega-3s help regulate the inflammatory response throughout the entire body.  When we consume omega-3s, they can be incorporated into cell membranes, influencing how cells communicate and respond to inflammatory signals, and they can shift inflammatory signaling toward a less inflammatory environment.⁷   

Not only do omega-3s themselves help regulate inflammation, but also they compete with other fatty acids to create downstream molecules, called lipid mediators, that further help with inflammation resolution.  Basically, having more omega-3 fatty acids available gives the body more raw material to produce different types of lipid mediators, and that includes SPMs.  As we discussed in Part 1, these SPMs have names like “resolvins,” “protectins,” and “maresins,” and both omega-3 DHA and EPA are involved in their production. 

DHA 

DHA (docosahexaenoic acid) is a precursor for several SPM families, including D-series resolvins, protectins, and maresins.  DHA is also particularly important to the nervous system.  It is a major structural component of cell membranes in the brain and retina and plays important roles in normal neural structure and function.⁸   

EPA 

EPA (eicosapentaenoic acid) is an important precursor for the E-series resolvins, including RvE1 and RvE2.  EPA also has its own biological effects.  By becoming incorporated into cell membranes and influencing lipid mediator production and inflammatory signaling, EPA can help regulate the body's inflammatory response independently of its role as an SPM precursor.⁹  

Together, DHA and EPA can influence inflammatory biology directly while also serving as precursors for SPMs involved in resolution. 

The problem is that over 90% of US adults consume less than the minimum recommended amount of omega-3 fatty acids, which has enormous implications on chronic inflammation and disease.¹⁰  

The Role of SPM Supplementation 

The body naturally produces SPMs, but production depends on available precursor molecules and the enzymes and signaling pathways involved. 

Simply consuming more omega-3s doesn't necessarily mean the body will produce more of every specific SPM.  This is one reason physicians and researchers are interested in direct SPM supplementation.  Rather than relying entirely on the body to convert dietary fatty acids into specific pro-resolving mediators, SPM supplementation provides the SPM compounds (or direct precursors of SPMs) themselves. 

However, supplemental SPMs don't replace omega-3s.  They address different parts of the same biological system.  Omega-3 fatty acids provide important structural and signaling functions and serve as precursors for SPMs, while SPMs are specialized signaling molecules involved in the resolution phase of inflammation. 

As we age and resolution pathways become more vulnerable to changes in production, signaling, and immune-cell function, it becomes more important to support both omega-3 availability and pro-resolving pathways. 

Supporting Resilience as We Age 

Aging doesn’t simply mean “more inflammation.”  Instead, aging is more about the balance between inflammation activation and resolution, making the body’s ability to respond, recover, and repair increasingly important.  Healthy lifestyle habits provide the foundation, and omega-3 fatty acids and SPMs represent an exciting area of established and growing research, with nutritional supplementation offering an opportunity to support both. 

Understanding this balance also helps put inflammaging into a larger context.  Its effects can extend beyond whole-body health, influencing the brain, cardiovascular system, joints, and physical recovery.  In Part 3, we’ll take a closer look at these connections and explore what inflammation resolution may mean specifically for these organ systems and for healthy aging overall.

References 

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