Inflammation: dealing with the chief of the body's inflammation fire department- NF-κBUpdated 2 years ago

In the field of longevity research, a key area of focus is the phenomenon known as "inflammageing," a term coined to describe the chronic low-grade inflammation that characterises aging [3].

Chronic inflammation was recently added as one of the 12 key hallmarks of ageing.

Persistent inflammation is believed to be a major risk factor for both morbidity and mortality in older adults, contributing to the development of age-related diseases such as cardiovascular disease, diabetes, cancer, and neurodegenerative diseases [3]. Therefore, managing this chronic inflammation is vital for promoting healthy aging and extending lifespan.

Dealing with the chief of the body's inflammation fire department NF-κB

Think of NF-κB as one of the key players, if we think of inflammation in terms of a fire in a city then the chief of the body's inflammation fire department is NF-κB. This chief is responsible for overseeing the body's response to emergencies, like infections or injuries [1]. It's involved in how the body responds to various triggers such as stress, germs, or even free radicals (molecules that can cause damage to your body's cells) [1].

Now, when the chief (NF-κB) is working as it should, it calls in the fire department (the inflammation response) at the right time, with the right intensity [1]. That's when we see the firefighters (IL-6 and TNF-α) getting to work [1].

But sometimes, the chief can get a little too zealous and trigger the emergency response even when it's not needed, or keep it going for too long [1]. When this happens, the inflammation fire department can cause more harm than good, leading to what we call 'excessive inflammation' [1].

This can be like a fire hose that's turned on full blast and left running – it can end up causing more damage than the fire it was supposed to put out!

So, while NF-κB is crucial in our body's defense mechanism, it's important it doesn't overdo its role, as that can lead to problems down the line [1].

Normal response to stress or infection

Stress or infection → Activation of NF-κB (The Chief) → Increase in TNF-α and IL-6 (The Firefighters) → Inflammation (Emergency Response) [1]

This is the usual process when the body is dealing with stress or infection. It's a necessary process to help the body recover. But if the chief (NF-κB) calls in the firefighters (TNF-α and IL-6) too much or too often, we end up with chronic inflammation, which can cause problems [1].

Now, enter our heroes CAT and SOD2. These guys are like the fire station's maintenance crew, they help to keep everything in balance [2]:

Maintaining the balance of inflammation

High levels of TNF-α and IL-6 → Activation of CAT and SOD2 (The Maintenance Crew) → Reduction of excessive inflammation [2]

In a healthy body, when the chief (NF-κB) becomes too overzealous and inflammation gets out of hand, the maintenance crew (CAT and SOD2) step in to bring things back to balance [2]. They work to reduce the intensity of the inflammation and help prevent the damage that excessive inflammation can cause [2].

In summary, we can look at inflammaiton in this way:

Stress or infection + NF-κB (overactive) → Too much TNF-α and IL-6 → Excessive inflammation + CAT and SOD2 → Balanced inflammation [1, 2]

See our article on managing inflammation to understand how you can rebalance chronic inflammation when it gets out of check.

References:

[1] Lawrence, T. (2009). The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harbor Perspectives in Biology, 1(6), a001651.

[2] Sies, H., Berndt, C., & Jones, D. P. (2017). Oxidative Stress. Annual Review of Biochemistry, 86, 715-748.

[3] Franceschi C, Campisi J. (2014). Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69 Suppl 1(Suppl 1), S4-S9.