Understanding Inflammaging: How Chronic Inflammation Drives Aging and Disease

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• What is Inflammaging?
• Chronic vs Acute Inflammation
• Senescent Cells and Inflammation
• Hormesis Explained
• The U-Shape of Exercise Benefit
• Personalized Exercise Approach
• Full Transcript

What is Inflammaging?

Dr. Andrea Maier, MD, defines inflammaging as a state of elevated inflammation in the body that increases with chronological age. This condition represents a fundamental biological process linking inflammation to the aging trajectory. Inflammaging is not a single disease but a systemic physiological state that underlies many age-related conditions. The term combines "inflammation" and "aging" to describe this progressive pro-inflammatory status.

Chronic vs Acute Inflammation

Dr. Andrea Maier, MD, makes a crucial distinction between acute and chronic inflammation. Acute inflammation serves a vital protective function against pathogens like bacteria and viruses. This temporary immune response helps fight infections and facilitates healing. Chronic inflammation, however, represents a persistent, low-grade state that damages tissues and organs over time. Dr. Andrea Maier, MD, emphasizes that while acute inflammation is necessary for survival, chronic inflammation drives pathological aging processes.

Senescent Cells and Inflammation

Senescent cells play a central role in driving inflammaging, as explained by Dr. Andrea Maier, MD. These are cells that have stopped replicating but remain metabolically active. Instead of functioning normally, senescent cells secrete inflammatory factors and signaling molecules. This constant secretion creates a pro-inflammatory environment that disrupts cellular homeostasis. The accumulation of these cells throughout tissues contributes significantly to the chronic inflammation characteristic of aging.

Dr. Anton Titov, MD, discussed with Dr. Maier how this process connects to age-related diseases. The persistent inflammatory signals from senescent cells create tissue damage that manifests as various chronic conditions. This understanding has led to research into senolytic therapies that target and remove these dysfunctional cells.

Hormesis Explained

Dr. Andrea Maier, MD, describes hormesis as a biological phenomenon where optimal cellular communication maintains homeostasis. This concept involves a beneficial response to mild stressors that strengthens cellular defense mechanisms. Hormetic stressors include moderate exercise, certain dietary components, and mild thermal stress. The principle follows that what doesn't kill you makes you stronger, at least at the cellular level.

Dr. Andrea Maier, MD, explains that hormesis represents the sweet spot where stress triggers adaptive responses without causing significant damage. This balanced state allows cells and organ systems to function at their optimal capacity. The interview with Dr. Anton Titov, MD, highlighted how understanding hormesis is crucial for developing effective anti-aging interventions.

The U-Shape of Exercise Benefit

Dr. Andrea Maier, MD, presents compelling evidence for a U-shaped relationship between exercise intensity and health benefits. Both extremes—sedentary behavior and excessive exercise—produce suboptimal outcomes. At the low end, insufficient activity leads to muscle atrophy, cardiovascular deconditioning, and metabolic dysfunction. At the high extreme, extreme exercise like marathon running can cause significant tissue damage and excessive inflammation.

The ideal exercise regimen falls in the middle of this U-shaped curve. Moderate, regular physical activity provides the hormetic stress needed to strengthen systems without overwhelming them. Dr. Andrea Maier, MD, notes that this optimal point varies significantly between individuals based on their training status, age, and overall health.

Personalized Exercise Approach

Dr. Andrea Maier, MD, emphasizes the critical need for personalized exercise prescriptions. What constitutes optimal exercise differs dramatically between a trained athlete and a sedentary individual. The goal is to find the exercise intensity and volume that maximizes benefits while minimizing inflammatory damage. This approach requires considering individual factors like current fitness level, age, health status, and recovery capacity.

Dr. Andrea Maier, MD, explains to Dr. Anton Titov, MD, that personalized exercise programming should balance muscle building and cardiovascular benefits against inflammatory costs. For untrained individuals, suddenly undertaking extreme exercise can cause more harm than good due to excessive muscle damage and inflammation. Conversely, appropriate progressive training builds resilience and improves inflammatory profiles over time.

Full Transcript

Dr. Anton Titov, MD: You also have discussed the concept of inflammaging in several of your papers. What is inflammaging?

Dr. Andrea Maier, MD: Inflammaging is a state with lots of inflammation in the human body. The aging part in inflammaging means that inflammation increases with chronological age.

So what does it mean? Inflammation is not bad because we know that if there is a bacteria or virus in our body, we need that inflammatory reaction to reduce the number of bacteria. After all, it's a stimulus for our immune system to fight that infection, which is very important. But this is acute inflammation.

What happens with the aging process is that there is chronic inflammation, and that's not good. We need acute inflammation because we have to attack bacteria or other things coming in from our environment. But we have to reduce chronic inflammation to a low level.

Chronic inflammation means that there is no homeostasis of cells. I will come back to the senescent cells. These cells do not replicate anymore, but they secrete inflammatory factors. They say, "Hey, I'm senescent. I'm not sure what I have to do."

Cells are secreting these inflammatory reactants; they provide the status of chronic inflammation. If something is chronic but it's not needed, that's damaging the surroundings of cells. This is what we see in age-related diseases.

There's a high state of chronic inflammation, where the immune system is up and running without the need to be up and running. So that is inflammaging.

Dr. Anton Titov, MD: In very strenuous exercise, there's been data that there is some negative remodeling that's going on. And that has to do with the concept of hormesis. What is hormesis? Can you briefly define it?

Dr. Andrea Maier, MD: Hormesis is a status where cells and the cellular system are communicating well. You need homeostasis, where the function of organ systems and tissue systems, and the cells in between, is communicating well. So you need that homeostasis to function optimally.

There could be extensive stressors from the outside, such as doing far too much exercise or doing very low amounts of exercise, which is sedentary behavior. Then the homeostasis is being dysregulated.

We see that we need a good frequency of exercise. We don't need too much exercise, which is damaging our system too much. I wouldn't say that running a marathon is bad. For some, it's fine.

But especially for untrained people, there will be so much damage in the muscle and myofibrils, which are the cells of the muscle being damaged. That always leads to so much inflammation that it's too much for the system because the system is not prepared for that. It's not in homeostasis.

On the other hand, if somebody has to do bed rest because of a fracture or some other medical reasons, or because of extreme sedentary behavior, it's the same. Too much is very bad for you because the homeostasis is destroyed and disturbed.

So exercise needs to be based on an individual level, a very personalized level. We need to find the optimal exercise level for individuals for the greatest benefit. It is for increasing muscle mass or muscle strength and cardiovascular fitness, versus not damaging the system too much with too much inflammation.

That is the reason why there's a U shape in how much exercise is being provided versus the benefits of it. So this is very important.

Dr. Anton Titov, MD: We discussed exercise. A lot is being said about dietary interventions.