The so-called Inflammatory aging (English). inflammaging) is one of the Hallmarks of Aging and is one of the most prominent age-related changes in cell-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.
In addition, in the section on cellular senescence we learned that senescent cells tend to release inflammatory substances into their environment. At the molecular level, the enhanced activation of NF-kB, a transcription factor and longevity pathway, leads to the development of inflammation. All of 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 at this point it is enough information that these substances are distributed throughout the body via the bloodstream and thereby disrupt communication between cells.
Inflammation and the immune system
Inflammation is also involved in the development of Obesity and type 2 diabetes mellitus. These two diseases have drastic effects on the body and are major contributors to accelerated aging in the human population. It is not for nothing that pathologies are at the top of the Global Burden of Disease Study. Inflammation also plays a role in the genesis of arteriosclerosis .
As inflammatory aging increases, immune system function subsequently declines. This has drastic consequences. This immunosenescence (see Senescence) can lead to poorer defense against infectious agents.
The resistance to tumors is also affected, especially since a functioning immune system also protects against malignant cells. Likewise, zombie cells in organs or muscle tissue in a functioning organism are eliminated by the immune system. Age-related or excessive inflammation limits all of this.
Intercellular communication and NF-kB
When research delved a little further into the depths of the molecular pathways in search of causes and thus possible ways to change inflammation, they came across the transcription factor NF-kB. Overactivation of NF-kB is typically associated with aging.
Based on this finding, some exciting experiments were carried out. In mice into which researchers introduced a gene that inhibits NF-kB, this led to a rejuvenation of the originally aged skin. In another study, also using a mouse model, genetic or drug inhibition of NF-kB prevented the appearance of typical features of aging.
Comparatively new is the discovery that Inflammation as well as the body's stress reactions activate NF-kB in the hypothalamus, resulting in a reduced release of GnRH (gonadotropin-releasing hormone). According to the name, GnRH ensures 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 of GnRH leads to brittle bones, weaker muscles or thinner skin. The list is even longer. In mice, GnRH treatment was able to slow the development of aging. The finding shows, on the one hand, the ability of the hypothalamus to modulate aging and, on the other hand, the diverse effects of NF-kB.
Changed inflammation levels in the blood as an indication
Medics have various parameters available to measure 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 system. Overall, it reacts very slowly and in the case of an acute infection it often only increases after 24 hours.
- Interleukin-6: This immune system messenger is produced by T helper cells and macrophages. As we get older, this messenger substance appears to be released in excess. 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 event of an infection, these can be increased. If you break down the leukocytes into their daughter cells (granulocytes, eosinophils), you can make more precise statements about the cause. A high number of eosinophils can be found e.g.b in allergic asthma.
- Procalcitonin: This peptide is produced in the C cells of the thyroid and is a marker for bacterial infection. In everyday clinical practice, this marker is used for the diagnosis/progression of sepsis.
As we age, some of these inflammatory levels 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. Macrophages are e.g.b phagocytes that eat everything that comes their way. T cells are another class in your immune army. They are white blood cells, where the T stands for thymus - the organ in which the T cells mature. The T cells have different tasks and are differentiated depending on their surface characteristics. T cells with the surface characteristic CD-8 (also known as T killer cells ) are involved in the defense against viruses.
What happens as we get older? It seems that a subtype of T cells is increasing. So-called Taa cells. These increase with age and appear to reduce inflammation with the help of the messenger substance Granzyme K+ to increase. At the same time, this change in the immune system ensures a weaker response to viruses. So it's not just the pro-inflammatory signaling pathways that are affected, but the defense cells of our immune system also seem to age.
Anti-inflammatory therapy as the key to longevity?
Now that we know that inflammation is one of the hallmarks of aging and contributes significantly to the aging process, the next logical step would be to treat this inflammation. Animal experiments have shown that improved health can be achieved by switching off some of the pro-inflammatory signaling pathways that go out of control with age.
But what do the data look like in humans? There is evidence that taking low-dose aspirin can reduce inflammation and thereby the frequency of the occurrence of arteriosclerosis decreases. However, ASA also has some side effects. Z.b It makes the blood thinner, so there is a risk of major bleeding if you fall. It also attacks the stomach lining and can cause ulcers.
In other studies, drugs that suppress the immune system, such as canakinumab, were administered to reduce the incidence of arterioclerosis, diabetes mellitus and hypertension. Research is going in a similar direction with the drug Rapamycin, which is described in detail in Peter Attia's book “Outlive”. becomes.
Conclusion on inflammaging as a hallmark of aging
The 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 with the other Hallmarks of Aging. Senescent cells contribute through the secretion of SASP , as do the epigenetic ones Changes with age.
Initial research approaches already exist to possibly reverse this Hallmark. From the regeneration of the thymus, to anti-inflammatory therapies with monoclonal antibodies, to the possibility of nutrition, fasting and secondary plant substances influence the inflammation.
The next article in this series is about the eleventh hallmark of aging: Dysbiosis.
