The so-called inflammaging (engl. inflammaging) is one of the Hallmarks of Aging and is one of the most prominent age-related changes in cell-to-cell communication. Inflammation has many causes. Accumulation of tissue damage, immune system failure, pathogens, or the body's inability to remove dead cells are just a few examples of this.
Additionally, we learned in the section on cellular senescence that senescent cells tend to release pro-inflammatory substances into their environment. On a molecular level, the increased activation of NF-kB, a transcription factor and longevity pathway, leads to the development of inflammation.All these circumstances ultimately ensure that a more or less large cell group produces a certain group of messenger substances: Interleukin-1b, tumor necrosis factor, and interferons.
Complicated names with even more complicated functions. For us, the information that these substances are distributed throughout the body via the bloodstream and thereby disrupt communication between cells is sufficient.
Inflammation and immune system
An inflammation is also involved in the development of obesity and type 2 diabetes. These two diseases have drastic effects on the body and contribute significantly to accelerated aging in the human population. It is no coincidence that the pathologies rank very high in the Global Burden of Disease Study.Even in the genesis of Atherosclerosis , inflammation has a role to play.
As the inflammatory aging increases, the function of the immune system subsequently decreases. This has significant consequences. This immunosenescence (see senescence) can lead to a poorer defense against pathogens.
The resilience against tumors is also affected, especially since a functioning immune system also protects against malignantly altered cells. Likewise, zombie cells in organs or in muscle tissue are eliminated by the immune system in a functioning organism. Age-related or excessive inflammation restricts all of this.
Intercellular Communication and NF-kB
As research delved deeper into the molecular pathways in search of causes and thus also possibilities for changing inflammation, it encountered the transcription factor NF-kB. An overactivation of NF-kB is typically associated with aging.
In line with this finding, some exciting experiments were conducted. In mice, where researchers introduced a gene to inhibit NF-kB, this led to a rejuvenation of the originally aged skin. In another study, also using a mouse model, the genetic or pharmacological inhibition of NF-kB prevented the occurrence of typical features of aging.
Relatively new is the discovery that inflammation and stress reactions of the body activate NF-kB in the hypothalamus and thus lead to a reduced release of GnRH (gonadotropin-releasing hormone). GnRH ensures, as the name suggests, that gonadotropins are released at the site of action. This is a group of hormones that is extremely important for reproduction and the production of sex hormones.
A deficiency in GnRH leads to bone fragility, weaker muscle or thinner skin. The list is even longer. In mice, GnRH treatment was able to slow down the aging process. This finding shows, on one hand, the ability of the hypothalamus to modulate aging and, on the other hand, the diverse effects of NF-kB.
Changed inflammatory values in the blood as an indication
Doctors have various parameters available for measuring inflammation. The most important are:
- C-reactive protein. Abbreviated CRP. This protein is produced in the liver and typically increases during an infection to activate the immune defense. It reacts overall very slowly and is often only elevated after 24 hours in an acute infection.
- Interleukin-6: This messenger substance of the immune system is produced by T-helper cells and macrophages. In older age, this messenger seems to be released excessively. Chronically high interleukin-6 levels are associated with poorer survival and contribute to inflammaging.
- Leukocyte count: The white blood cells represent the entirety of our immune cells. In the case of an infection, these may be elevated. By breaking down the leukocytes into their daughter cells (granulocytes, eosinophils), one can potentially make more precise statements about the cause. A high number of eosinophils can be found z.B. in allergic asthma.
- Procalcitonin: This peptide is produced in the C-cells of the thyroid gland and is a marker for a bacterial infection. In clinical practice, this marker is used for the diagnosis/monitoring of sepsis.
With age, some of these inflammatory values increase and thus contribute to the development of diseases.
Changed T-cells – the immune army is weakened
You can imagine our immune system as a large army. There are very different actors involved. Macrophages are z.B. Eating cells that devour everything that comes their way. T-cells are another class in your immune army. They are part of the white blood cells, where the T stands for thymus – the organ where T-cells mature. T-cells have different tasks and are distinguished based on surface characteristics. T-cells with the surface marker CD-8 (also known as T-killer cells are involved in the defense against viruses.
What happens as we age? It seems that a subtype of T-cells is increasingly on the rise. So-called Taa cells. These increase with age and seem to enhance inflammation with the help of the messenger substance Granzyme K+ . At the same time, this change in the immune system leads to a weaker response to viruses. So, it is not only the pro-inflammatory signaling pathways that are affected, but also the defense cells of our immune system seem to age.
Anti-inflammatory therapy as the key to Longevity?
Now that we know that inflammaging is one of the hallmarks of aging and significantly contributes to the aging processes, the next logical step would be to want to treat this inflammation.In animal experiments, it has been shown that by shutting down some of the pro-inflammatory signaling pathways that go awry with age, improved health can be achieved.
But what do the data look like in humans? There is evidence that by taking low-dose aspirin inflammation can be reduced, thereby decreasing the frequency of arteriosclerosis. However, aspirin also has some side effects. Z.B It makes the blood thinner, so that in case of falls, there is a risk of greater bleeding. Additionally, it affects the stomach lining and can cause ulcers there.
In other studies, medications that suppress the immune system, such as Canakinumab, were administered to reduce the incidence of arteriosclerosis, diabetes mellitus, and hypertension. Research is also moving in a similar direction with the medication Rapamycin, which is extensively described in Peter Attia`s book "Outlive".
Conclusion on Inflammaging as a Hallmark of Aging
The inflammatory aging (Inflammaging) plays an important role in the aging process. However, it is very difficult to consider this as a single factor; rather, it is jointly responsible for aging along with the other Hallmarks of Aging. Senescent cells contribute through the secretion of SASP just as the epigenetic changes with age.
Initial research approaches already exist to possibly reverse this hallmark.From the regeneration of the thymus, through anti-inflammatory therapies with monoclonal antibodies to the possibility of influencing inflammation through nutrition, fasting and secondary plant substances .
In the next article of this series, we will discuss the eleventh characteristic of aging: dysbiosis.
