The so-called inflammaging is one of the hallmarks of ageing 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 body's inability to remove dead cells are just a few examples.
In addition, we learned in the section on cellular senescence that senescent cells tend to release pro-inflammatory substances into their environment. At the molecular level,enhanced 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 group of cells produces a certain group of messenger substances: interleukin-1b, tumor necrosis factor and interferons .
Complicated names with even more complicated functions. At this point, it is sufficient for us to know that these substances are distributed throughout the body via the bloodstream and thus 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 a drastic impact on the body and make a major contribution to accelerated ageing in the human population. It is no coincidence that these pathologies are at the forefront of the Global Burden of Disease Study. Inflammation also plays a role in the development of arteriosclerosis .
When inflammation increases, the function of the immune system decreases . This has drastic consequences. This immunosenescence (see senescence) can lead to a poorer defense against infectious pathogens.
Resistance to tumors is also affected, especially as a functioning immune system also protects against malignant cells. Similarly, zombie cells in organs or 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
When researchers began to delve deeper into the molecular pathways in their search for the causes of inflammation and thus also ways of modifying it, they came across the transcription factor NF-kB . Overactivation of NF-kB is typically associated with ageing.
Following on from this finding, some exciting experiments have been carried out. In mice in which 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 drug-induced inhibition of NF-kB prevented the appearance of typical signs of ageing.
The discovery that inflammation as well as stress reactions of the body, activate NF-kB in the hypothalamus and thus lead to a reduced release of GnRH (gonadotropin-releasing hormone) is comparatively new. 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 bone fragility, weaker musculature or thinner skin. The list goes on. In mice, GnRH treatment was able to slow down the aging process. This finding demonstrates the ability of the hypothalamus to modulate ageing on the one hand and the diverse effects of NF-kB on the other.
Changed inflammation levels in the blood as an indication
Medical professionals have various parameters at their disposal to measure inflammation. The most important are:
- C-reactive protein . Abbreviated to CRP. This protein is produced in the liver and typically rises during an infection to activate the immune defense. Responds very slowly overall 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 old age, this messenger substance appears to be released in excess. Chronic 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. They can be elevated during 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 is 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 everyday clinical practice, this marker is used for the diagnosis/progression of sepsis.
Some of these inflammatory values increase with age 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 players. Macrophages arez.B . Scavenger cells that devour everything that gets in their way. T cells are another class in your immune army. They belong to the 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 according to their surface characteristics. For example, T cells with the surface characteristic CD-8 (also known as T killer cells ) are involved in the defense against viruses.
What happens in old age? It seems that a subtype of T cells increases more and more. So-called Taa cells. These increase in number with age and appear to increase inflammation with the help of the messenger substance Granzyme K + . At the same time, this change in the immune system results in a weaker response to viruses . It is therefore not only the pro-inflammatory signaling pathways that are affected, but the defense cells of our immune system also appear to age .
Anti-inflammatory therapy as the key to longevity
Now that we know that inflammaging is one of the hallmarks of aging and a major contributor to the aging process, the next logical step would be to treat this inflammation. In animal experiments, it was shown that by switching off some of the pro-inflammatory signaling pathways that get out of hand in old age, improved health could be achieved.
But what does the data look like in humans? There is evidence that taking low-dose ASA can reduce inflammation and thereby reduce the incidence of atherosclerosis . However, ASA also has some side effects. Z.B . it makes the blood thinner, so that there is a risk of major bleeding in the event of a fall. It also attacks the stomach lining and can cause ulcers.
In other studies, drugs that suppress the immune system, such as canakinumab , have been administered to reduce the incidence of arteriosclerosis, diabetes mellitus and high blood pressure. Research with the drug Rapamycin , which is described in detail in Peter Attia 's book "Outlive", is moving in a similar direction.
Conclusion on inflammaging as a hallmark of ageing
The inflammaging plays an important role in the ageing process. However, it is very difficult to consider this as a single factor, rather it is jointly responsible for ageing with the other hallmarks of ageing. Senescent cells contribute through the secretion of SASP as do the epigenetic changes in aging .
First 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 to influence inflammation.
The next article in this series is about the eleventh hallmark of aging: Dysbiosis .
