Break the loop
Many mechanisms of aging work on the principle of direct or indirect positive feedback: A strengthens B, while B, in turn, aggravates A. Or does A lead to B, which causes C, burdening A.
Chronic inflammation – the continuous and tissue–damaging activation of the immune system - is involved in many circular relationships and feedback loops. The article cited below from the journal Frontiers in Cardiovascular Medicine, which is in the public domain, briefly mentions known factors contributing to the development of inflammation during aging.
Inflammation is an important mechanism by which the immune system coordinates its functions with those of other tissues in order to resist pathogens and respond to damage. For a short time, this is beneficial; with constant inflammation, on the contrary, there is a violation of the processes of regeneration and maintenance of tissue integrity, the risk of cancer increases, and the progression of many diseases accelerates. Inflammatory conditions associated with aging include osteoarthritis, various forms of fibrosis, almost all neurodegenerative diseases, atherosclerosis and many others.
What causes an increase in the severity of chronic inflammation in the elderly? The primary causes are the forms of molecular damage described in the concept of "rejuvenating biotechnology" formulated by SENS Foundation specialists, but the boundary between the root cause and age-related inflammation is clearly defined only in some cases.
Aging is an expanding, extremely complex, multi-layered system of causes and effects, growing out of several fundamental forms of tissue damage that affect each other. Therefore, it is obvious that the immediate causes of the development of chronic inflammation are very complex.
It is easy enough to say that it is partly due to signaling molecules released by cells that have entered the phase of physiological aging, which, among other things, are involved in the extinction and disruption of the functioning of the immune system in old age. However, these brief sentences describe an incredibly complex biochemical system, deciphered only to a small extent.
At the same time, there are several simple techniques that allow us to approach an effective method of regulating certain sources of inflammation during aging. Selective destruction of cells that have entered the phase of physiological aging eliminates their inflammatory effect, while there is no need to decipher the corresponding mechanisms to obtain the effect.
Similarly, the elimination of all immune cells, followed by cell therapy to accelerate the resumption of their populations, is a viable approach to solving a number of problems of the aging immune system, leading to an aggravation of inflammation.
Perhaps the restoration of the ability of the thymus to produce a large number of new immune cells can benefit. These and some other credible approaches do not require large amounts of new knowledge and to a large extent make it possible to circumvent the problem of the lack of information about the biochemical mechanisms of inflammatory aging. In some cases, the cause of what is happening does not matter much, provided there is a sufficiently multifaceted approach to eliminating the consequences or other solutions to the problem.
From an article by Fumihiro Sanada et al. Source of Chronic Inflammation in Aging (Sources of chronic inflammation in aging), published in the journal Frontiers in Cardiovascular Medicine:
"Today, chronic inflammation is considered a risk factor for the development of a wide range of age-related diseases, such as hypertension, diabetes mellitus, atherosclerosis and cancer. The costs associated with unhealthy aging associated with lifestyle are continuously increasing in both developed and developing countries. Therefore, finding out the causes and cellular mechanisms of chronic inflammation is a top priority.
There are several factors that presumably initiate and support sluggish inflammation. These include: aging, an unbalanced diet, low levels of sex hormones and smoking. In contrast to the young, the elderly have constantly elevated levels of pro-inflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), which can induce muscle tissue atrophy and the development of malignant tumors through DNA damage. The visceral adipose tissue of obese people can also produce both IL-6 and TNF-alpha, which affect systemic metabolism. The accumulation of macrophages in visceral fat is proportional to the body mass index and, apparently, is the main cause of sluggish chronic systemic inflammation and tissue resistance to insulin in obese people. Chronic smoking increases the production of the same pro-inflammatory cytokines, as well as interleukin-1-beta, increases systemic inflammation and is an independent risk factor for a number of lifestyle-related diseases.
Acute inflammation is a necessary component of the immune response to pathogens entering the body and acute traumatic injuries. It makes it possible to restore and renew cells in many tissues. Chronic inflammation, on the contrary, usually leads to sluggish non-attenuating inflammatory processes leading to tissue degeneration. Chronic sluggish inflammation is a critical factor leading to the development of various age-related pathologies and natural processes occurring in aging tissues, including the nervous system and musculoskeletal system. Many tissues of the elderly suffer from chronic inflammation, and pro-inflammatory cytokines are known for their ability to weaken the anabolic (enhancing protein synthesis) signaling cascade, including signaling mechanisms mediated by insulin and erythropoietin, which leads to the development of sarcopenia.
The accumulation of cellular debris and immunoglobulins due to malfunctions of the system of getting rid of dead cells in old age triggers the activation of the immune system, which leads to the development of persistent inflammation. Among the complex factors that determine the aging process, for a certain time, special attention has been drawn to mitochondrial dysfunction. The consequences of age-related deterioration of mitochondrial quality control include the release of damage-associated molecular structures of mitochondrial origin. Such structures, especially circulating cell-free mitochondrial DNA, have recently become the object of intensive study due to their possible involvement in the development of conditions associated with inflammation, such as aging and degenerative diseases. Due to their bacterial origin, these molecules contribute to the intensification of inflammatory reactions by interacting with receptors similar to those involved in the immune system's responses to pathogens.
The effectiveness of the barrier formed by the mucous membrane of the oral cavity and intestines, which prevents the invasion of bacteria into the body, decreases with age. Periodontal diseases (periodontal disease) also lead to the development of chronic sluggish inflammation. The diversity of the intestinal microbiome decreases in old age, including by reducing the number of microorganisms that have anti-inflammatory effects. At the same time, the number of inflammation-associated and pathogenic microflora increases with age.
Physiological aging of a cell is defined as an irreversible stop of the cell cycle triggered by a number of mechanisms. It is obvious that the number of cells of various organs that have entered this phase increases with aging. Such cells secrete many pro-inflammatory cytokines, causing the development of sluggish inflammation. The phenotype of cells that have entered the phase of physiological aging is commonly referred to as the "secretory phenotype associated with physiological aging" (senescence-associated secretory phenotype, SASP). Recently, it is believed that it is the main cause of the development of "inflamaging" both with aging and with age-related diseases such as atherosclerosis, cancer and diabetes mellitus. A growing body of scientific evidence suggests that the elimination of cells that have entered the phase of physiological aging in animal models slows down the progression of age-related diseases, including atherosclerosis and osteoarthritis. These data are convincing evidence in favor of the hypothesis that the destruction of cells that have entered the phase of physiological aging, their reprogramming, as well as the modulation of pro-inflammatory mechanisms associated with the formation of SASP, are potential anti-aging strategies aimed at combating age-related diseases and increasing the duration of a healthy human life.
Physiological aging of the immune system, which is an age-related violation of the regulation of innate immune reactions, is characterized by persistent immune reactions. It increases the predisposition to the development of malignant neoplasms, autoimmune and infectious diseases, reduces the strength of the reaction to vaccination, and also disrupts the healing processes of wounds. On the other hand, chronic inflammation can accelerate the process of physiological aging of the immune system. The mechanisms underlying persistent aging-associated inflammation are not fully clear today, however, apparently, they include changes in the number and functions of cells that form innate immunity. Changes in the expression of receptors for recognition of standard molecular structures characteristic of pathogens, their activation under the action of endogenous ligands associated with cellular damage, and the launch of abnormal molecular signals after activation of these receptors are involved in the induction of chronic cytokine secretion. Thus, in combination with the physiological aging of cells, a violation of the regulation of immunological memory mediated by innate immunity can also contribute to the development of persistent sluggish inflammation that persists even after the elimination of the primary stimulus.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of FightAging!: What Causes the Chronic Inflammation of Aging?