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, failure of the immune system, pathogens or the inability of the body to remove dead cells are just a few examples.
In addition, in the section on cellular senescence learned that senescent cells tend to release inflammatory substances into their environment. At the molecular level, the increased activation of NF-kB, a transcription factor and longevity path, 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, it is enough to know that these substances are distributed throughout the body via the bloodstream and thereby disrupt communication between cells.
inflammation and immune system
Inflammation is also involved in the development of Obesity and type 2 diabetes mellitus involvedThese two diseases have drastic effects on the body and make a major contribution to accelerated aging in the human population. It is not without reason that these pathologies are at the forefront of the Global Burden of Disease Study. Even in the genesis of arteriosclerosis Inflammation plays a role.
As inflammation ages, the immune system function declinesThis has drastic consequences. This immunosenescence (see Senescence) can lead to a poorer defense against infectious pathogens.
Resistance to tumors is also affected, especially since a functioning immune system also protects against malignant cells. Zombie cells in organs or muscle tissue are also eliminated by the immune system in a functioning organism. Age-related or excessive inflammation limits all of this.
Intercellular Communication and NF-kB
When research delved deeper into the molecular pathways in search of causes and thus also possibilities for changing inflammation, the transcription factor NF-kBOveractivation 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 to inhibit NF-kB, This led to a rejuvenation of the originally aged skinIn another study, also using a mouse model, genetic or drug inhibition of NF-kB prevented the appearance of typical features of aging.
The discovery that inflammation and stress reactions of the body, NF-kB in the hypothalamus activate and thus to a reduced release of GnRH (gonadotropin-releasing hormone).As the name suggests, 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 lack of GnRH leads to brittle bones, weaker muscles or thinner skin. The list is even longer. In mice, GnRH treatment was able to slow down the aging process. This 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 values in the blood as an indication
Doctors 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 infectionto activate the immune system. Reacts very slowly overall and is often only increased after 24 hours in the case of an acute infection.
- interleukin-6: This messenger substance of the immune system is produced by T helper cells and macrophages. This messenger substance seems to be released in excessive amounts in old age. Chronically high interleukin-6 levels are associated with poorer survival and contribute to inflammaging.
- leukocyte count: The white blood cells represent all of our immune cells. These can be increased in the case of an infection. If the leukocytes are broken down into their daughter cells (granulocytes, eosinophils), it may be possible to make more precise statements about the cause. A high number of eosinophils can be found in allergic asthma, for example.
- procalcitonin: This peptide is produced in the C cells of the thyroid and is a marker for a 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 contribute to the development of diseases.
Altered T cells – the immune army is weakened
You can imagine our immune system as a large army. There are many different players. Macrophages, for example, are phagocytes that eat up everything that comes their way. T cells are another class in your immune army. They are white blood cells, where T stands for thymus – the organ in which T cells mature. T cells have different tasks and are differentiated according to their surface characteristics. T cells with the surface characteristic CD-8 (also known as T killer cells known) is involved in the defense against viruses.
So what happens as we age? It seems that a subtype of T cells increases in number. So-called Taa cells. These increase with age and seem 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. Not only the proinflammatory signaling pathways 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 inflammaging is one of the hallmarks of aging and contributes significantly to the aging process, the next logical step would be to try to treat this inflammation. Animal experiments have shown that by eliminating some of the pro-inflammatory signaling pathways that go out of control with age, improved health can be achieved.
But what do the data look like in humans? There is evidence that taking low-dose aspirin the inflammation can be reduced and thereby the The incidence of arteriosclerosis is decreasingHowever, ASS also has some side effects. For example, it thins the blood, so that if you fall, there is a risk of major bleeding. It also attacks the stomach lining and can cause ulcers.
In other studies, drugs that suppress the immune system, such as canakinumab, administered to reduce the incidence of arterioclerosis, diabetes mellitus and hypertension. Research is moving in a similar direction with the drug Rapamycin, which is used in Peter Attia`s book “Outlive” is described in detail.
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, much more it is related to the other Hallmarks of Aging are jointly responsible for aging. Senescent cells contribute to the secretion of SASP as well as the epigenetic changes in aging.
Initial research approaches already exist to potentially reverse this hallmark. From the regeneration of the thymus, to anti-inflammatory therapies with monoclonal antibodies, to the possibility of Nutrition, Fast and secondary plant substances to influence the inflammation.
The next article in this series is about the eleventh hallmark of aging: dysbiosis.
