illustration of the brain anatomy with a network overlaying it.

Neuroinflammation in aging and disease

Our bodies are equipped with a variety of ways to fight cellular stress. Whether the origins of this stress are internal or external, inflammation is one of the most important defense mechanisms we have set in place. If we acquire burns, cuts, or insect bites, inflammation produces redness and swelling surrounding the injured area. When foreign pathogens (whether bacterial, viral, or fungal) invade our bodies, the inflammation response can be strong enough to give us fevers, induce body aches, and make us exhausted.

What is inflammation?

Biologically, inflammation occurs when stressors irritate cells and cause them to release molecules that alert their neighbors. These inflammatory signals trigger a complex cascade of events that help protect the tissue (by changing cellular fuel or recruiting immune cells to fight pathogens, for example). It’s a short-lived response that’s meant to serve as a beacon, directing the immune system to the source of disruption. This short-lived inflammation is vital for proper physiological function, and for our body’s survival when faced with illness and disease. However, if these inflammatory signals become chronically released, it can lead to a variety of issues, including the death of healthy cells.  

Interestingly, as we age, there is an increase in inflammation throughout the body, even in the absence of disease or infection. This “chronic, low-grade inflammation” is a prominent molecular hallmark of aging known as inflammaging, and it’s a strong risk factor for diseases that are frequently observed in older individuals. Higher levels of chronic inflammation contribute to more than half of deaths worldwide and are associated with a variety of diseases, including autoimmune diseases, cardiovascular disease, gastrointestinal disorders, lung diseases, mental illnesses, metabolic diseases, neurodegenerative diseases, and cancer.

Changes in inflammation as we succumb to diseases and older age are relevant to the entire body, so it comes as no surprise that inflammation levels can impact brain health as well.

Inflammation and the brain

The brain has a special barrier (i.e., the blood-brain-barrier) that separates it from the rest of the body. This means that the immune system can’t enter the brain to keep it healthy; instead, the brain houses its own specialized immune cells not found anywhere else in the body, called microglia. Because microglia are unique to the brain, the cascade of inflammatory signaling that leads to neuroinflammation is slightly different than in the rest of the body.

Microglia are responsible for the cellular maintenance and repair that our peripheral immune system would usually take care of. This involves defending against foreign invaders, dealing with internal stressors, and of course, initiating an inflammation response. Just like the rest of the body, as we age, these brain-exclusive immune cells begin to deteriorate and chronically release inflammatory signals (neuroinflammaging). Just as before, these signals are meant to be transient beacons, but they become permanently turned on and then contribute to cognitive decline, impaired motor skills, and deficits with learning and memory. Neuroinflammaging also makes the brain more susceptible to age-related diseases, like Alzheimer’s, Parkinson’s, and ALS.

Takeaway

There is a lot that scientists still don’t understand about the phenomena of inflammation, but whether it’s occurring in the brain or elsewhere in the body, so far it seems:

  • That small levels of short-lived inflammation are an essential defense mechanism against various cellular stressors.
  • That small levels of chronic inflammation can be associated with healthy aging, but chronic inflammation also predisposes us to a variety of diseases, such as cardiovascular and neurodegenerative diseases.
  • That high levels of chronic inflammation are detrimental to health and are often associated with terminal illnesses.

As we progress through life, chronic inflammation seems to be inevitable. Still, minimizing inflammatory levels to the extent we can has shown to have a beneficial effects on health and even lifespan.

Thankfully, the things you can do to positively impact inflammatory signaling will not only help your body, but will also help your brain! Ways to impact your inflammation levels day to day include:

To learn more about inflammaging, check out the Center’s September 2020 blog about “the side effect of age you haven’t heard of.”

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ABOUT THE AUTHOR

Randy Grant is a Ph.D student and part of the Healthspan Biology Lab in CSU’s Department of Health and Exercise Science. Studying chronic inflammation in the aged brain, Randy hopes to elucidate the fundamental physiology involved with its regulation and progression in disease.

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