Aging is a process of damage and consequence. Damage to the molecular machinery of cells and the molecular structure of tissues accumulates as a normal consequence of the operation of healthy metabolism. This damage degrades function, producing a lengthy chain of downstream consequences that interact with one another, make one another steadily worse, and culminate in age-related disease. Some of these downstream consequences are more important than others. Among the most important are raised blood pressure, which converts low level molecular damage into actual structural pressure damage to tissues, and chronic inflammation, which converts low level molecular damage into sweeping failure and detrimental change of cell and tissue function.
These two downstream consequences of damage are so influential over the development and progression of age-related disease that some progress has been made in lowering age-related mortality by crudely forcing reductions in blood pressure and inflammation, with no effort to eliminate the causes of these issues. Most efforts to tackle inflammation involve sabotaging the cell signaling that drives it. This is a blunt tool, as transient inflammation is quite important to health. Only the inappropriate chronic inflammatory signaling should be suppressed, but the tools of the past are far from being discriminating enough in this matter.
A sizable degree of the chronic inflammation of aging is driven by the presence of senescent cells and the inflammatory signaling that they generate. Numerous mechanisms create senescent cells, and they are useful in the short term, a necessary part of wound healing, cancer suppression, and other mechanisms. The issue is that clearance of these cells fails with age, and thus their numbers grow inexorably. Fortunately, the advent of senolytic therapies to selectively destroy senescent cells offers considerable potential as a way to reduce only the undesirable chronic inflammation of aging, while preserving desirable transient inflammation. Given the importance of inflammation in aging, we might expect considerable benefits to emerge from the use of senolytics.
"Today, chronic inflammatory diseases are at the top of the list of death causes. There is enough evidence that the effects of chronic inflammation can be observed throughout life and increase the risk of death. It's no surprise that scientists' efforts are focused on finding strategies for early diagnosis, prevention and treatment of chronic inflammation."
One of the serious results obtained to date has been the concept of immune aging, which enables researchers to characterize the immune function of an individual and to predict the causes of mortality much more accurately than by relying only on chronological age. In addition to well-known inflammation biomarkers, such as C-reactive protein, interleukin 1 and interleukin 6, tumor necrosis factor, scientists note the need to study additional biomarkers of the immune system, which differ very much from person to person, in particular, the subgroups of T-lymphocytes and B-lymphocytes, monocytes, etc.
Scientists have identified certain factors (social, environmental and lifestyle factors) that contribute to systemic chronic inflammation. Taken together, such factors are the main cause of disability and mortality worldwide. An integrative approach to the study of mechanisms of systemic chronic inflammation is being adopted by a growing number of scientists. Research is continuing, and scientists have a long way to go to fully understand the role of chronic inflammation in aging and mortality, and to be able to predict changes in a person's health throughout life.
Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, and autoimmune and neurodegenerative disorders. We describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants, and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.