Rethinking Inflammation, Part 3: Inflammaging and Whole-Body Health

In Part 1 of our Rethinking Inflammation series, we explored the body's active process for bringing inflammation to a close, known as resolution, and the specialized pro-resolving mediators (SPMs) that coordinate it. 

In Part 2, we looked at how aging can affect the immune system and resolution pathways, making it harder for the body to resolve inflammatory responses fully.  Over time, this can contribute to inflammaging, a chronic, low-grade inflammatory state that is a hallmark of the aging process. 

But where does this matter in the body? 

Here in Part 3, we'll look at how inflammaging and impaired resolution may affect four different body systems.  We'll also bring together what we've learned about omega-3 fatty acids and SPMs and their potential role in supporting resolution for healthier aging. 

How Aging Changes Inflammation 

Under normal circumstances, inflammation is meant to be self-limiting.  The body responds to a threat, addresses the problem, and then shifts toward resolution (i.e., the inflammation terminates). 

Aging, however, can affect multiple parts of this process.  Changes in immune-cell function, cellular signaling, enzyme activity, and the pathways involved in producing and responding to SPMs may make resolution less efficient.¹  That is, the aging process reduces the body’s capacity to make SPMs, and it makes the resolution networks that are meant to respond to SPMs less efficient.  This contributes to feedback loops, where an aging and less effective immune system is turned “on,” but the resolution process is impaired (including the production of SPMs), leading to more tissue damage, which triggers continued inflammation.²   

When inflammatory activity persists, its effects can extend throughout the body and look very different depending on where it occurs.  Now we’ll dive into how current evidence links inflammaging to changes in tissues and systems involved in:³  

• Brain health,  
• Cardiovascular health,  
• Joints and mobility, and  
• Physical resilience and recovery. 

Neuroinflammation and the Aging Brain 

Have you noticed that your brain doesn't always feel quite as quick as it once did?  Maybe a name takes longer to come to mind, concentrating requires more effort, or a mentally demanding day leaves you feeling unusually drained. 

These experiences can have many causes and do not necessarily indicate a problem with your brain.  However, they raise an interesting question about how inflammatory changes may affect the aging brain. 

The brain has its own immune cells, called microglia, which constantly monitor their surrounding brain tissue.  These cells are essential for protecting the brain and clearing damaged material.  But, like inflammation elsewhere in the body, immune activity in the brain needs to be appropriately regulated and resolved.  When neuroinflammatory signaling becomes persistent, it can contribute to cognitive aging and neurodegenerative diseases.³   

This has raised interest in whether supporting resolution pathways could help maintain a healthier inflammatory environment in the aging brain and protect against decline.  SPMs are an especially promising area of this research.  Resolvins, protectins, and maresins (types of SPMs) have all been studied for their effects on inflammatory signaling and immune-cell behavior in neural tissue.⁴   

One particularly interesting example is a DHA-derived SPM produced in neural tissues specifically called neuroprotectin D1 (NPD1), suggesting a potential role in cognitive health.  Early research found that NPD1 could support neural cell survival and influence inflammatory and cell-death signaling.  Furthermore, it was discovered that in human brain tissue from people with Alzheimer's disease, DHA and NPD1 were reduced in certain regions.  These findings have brought attention to NPD1 and other SPMs as important regulators of brain inflammation.^5,6  

Need a refresher on SPMs, like resolvins, protectins, and maresins? Revisit Part 1. 

Inflammation and Cardiovascular Health 

The cardiovascular effects of inflammaging may not be as obvious through symptoms.  Instead, you might notice that endurance activities feel more demanding than they once did, or that your stamina isn't quite what it used to be.   

While inflammation in the blood vessels generally isn't something you can feel directly, it can influence the health of the vascular system over time.  Atherosclerosis, for example, involves ongoing inflammatory activity within arterial plaques, and when resolution doesn't work effectively, inflammatory cells and damaged cellular material can accumulate within these plaques.⁷  SPMs are involved in several processes that help resolve this inflammation, including clearing damaged cells.⁸ 

Omega-3 fatty acids have a much longer history of cardiovascular research than SPMs themselves.  One well-established effect is lowering triglycerides, and clinical studies have also found that omega-3 supplementation can influence certain markers of systemic inflammation.⁹  Researchers are also studying SPMs as another piece of this puzzle, investigating how both omega-3-derived SPMs may influence vascular inflammation and resolution.¹⁰  

The Impact on Joints and Mobility 

Sometimes aging doesn't feel like an injury or an illness; it can feel like movement taking a little more effort than it used to.  You may notice stiffness when you first get out of bed, need more time to warm up before exercising, or find that a long walk, hike, workout, or weekend project leaves you sore for longer than it once did. 

Inflammatory changes that occur with aging can contribute to corresponding changes in joint tissues and are closely linked to osteoarthritis and declining joint function.¹¹  In this case, resolution plays an important role in transitioning the body from inflammation to tissue repair. 

Omega-3 fatty acids may support this process in several ways.  A recent review examined how omega-3s can influence inflammatory pathways in joint tissue, including signaling molecules that contribute to inflammation and tissue breakdown.  Because omega-3s also serve as precursors for specialized pro-resolving mediators, this has prompted interest in their potential role in supporting resolution and repair.¹²  

For healthy aging, maintaining effective resolution pathways may support joint comfort, ease of movement, and overall mobility so you can keep doing the daily activities you enjoy. 

Resilience, Exercise, and Recovery 

Closely related to joints and mobility just mentioned, one of the most recognizable signs of aging isn't daily pain or stiffness — it's a gradual loss of resilience, the ability to “bounce back” after stress and challenges.  You can still do the workout.  You can still take the trip.  You can still stay up late.  What changes is how long it takes to recover afterward. 

Exercise is the activity where most people can clearly feel their resilience building up, maintaining, or declining.  Exercise is also one of the most important tools we have for healthy aging, supporting cardiovascular, metabolic, brain, and muscle health, while helping maintain physical function.  But exercise also creates physical stress.  A challenging workout naturally triggers inflammation as part of the process of sensing stress, repairing tissue, and adapting to the demands placed on the body.  That response, however, is not something we want to eliminate.   

Resolution helps move the body from the initial inflammatory response toward recovery, repair, and tissue regeneration.  Longer recovery times after exercise and other physical stresses are driven in part by aging immune function and resolution pathways that are not as efficient as they once were. 

Omega-3s have been studied extensively for their role in recovery.  A 2026 systematic review and meta-analysis found that omega-3 supplementation may improve several measures of recovery following exercise-induced muscle damage, including muscle soreness, swelling, strength, and range of motion.¹³  Research specifically examining SPMs and exercise recovery is newer, and early studies suggest that resolution pathways are involved in the repair and adaptation that follow exercise.¹⁴  

The goal isn't to eliminate the inflammation that comes with exercise.  It's to support the body's ability to move efficiently from stress and inflammation toward recovery, repair, and adaptation.  That ability to bounce back is an important part of resilience and healthy aging. 

Omega-3s, SPMs, and the Resolution Response 

We've seen why resolution matters across the brain, cardiovascular system, joints, and physical recovery.  But what does the research tell us about using omega-3s and SPMs to support these pathways? 

As we discussed in Part 2, DHA and EPA have their own effects on inflammatory signaling, while also serving as precursors for several SPM families.  But the body must convert these fatty acids through a series of enzymatic steps, and aging and other biological factors can affect those pathways. 

These changes may create a gap between the body's need for resolution signals and its ability to produce them efficiently.  Providing SPMs or their direct precursors (called PRMs) may offer additional support further downstream in the resolution process, rather than relying entirely on the body's ability to produce each mediator from its original fatty acid building blocks. 

In a randomized, double-blind, placebo-controlled study, Souza and colleagues found that an enriched marine oil supplement increased circulating SPM concentrations and altered immune-cell responses in healthy adults.¹⁰  Other evidence shows that different omega-3-enriched oils can produce different SPM profiles, suggesting that the type and composition of an omega-3 supplement may influence its biological effects.¹⁵ 

A recent pilot study used phospholipid-rich herring roe oil providing DHA and EPA.  After two weeks, healthy young adults had lower triglycerides and higher HDL cholesterol, along with improvements in glucose tolerance.¹⁶ 

In a 2023 randomized, placebo-controlled trial, adults with symptomatic knee osteoarthritis who took an SPM-enriched supplement for 12 weeks experienced greater reductions in pain than those taking placebo.  The SPM group also reported improvements in quality of life, including their ability to carry out usual activities.¹⁷  Joints, mobility, and recovery are among the most exciting areas of omega-3 and SPM research — not only for aging adults, but for athletes, as well. 

Together, these studies show how research on omega-3s and SPMs has moved beyond basic mechanisms into human trials examining inflammation, immune function, metabolic health, and joint health.  There’s still much to learn about resolution physiology, but the underlying theme of our inflammation series is that supporting the body's ability to resolve inflammation is an important part of maintaining healthy function and improving resilience, especially as we age. 

Rethinking Inflammation 

Across this three-part series, we’ve explored inflammation from a different perspective: first, how the body actively resolves inflammation; then, how aging can make that process less efficient; and finally, what those changes can mean for the brain, cardiovascular system, joints, and physical recovery. 

Inflammation is a normal and necessary part of how the body responds to stress, injury, and threats.  The ability to resolve that inflammation and return to balance is just as important, and supporting that process can help preserve our resilience. 

Omega-3s and SPMs may support the body's resolution pathways, and research continues to explore their role in healthy aging.  Ultimately, healthy aging isn't about eliminating inflammation.  It's about maintaining the ability to respond, resolve, recover, and repair. 

References 

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