Immunosenescence and Inflammaging, Two Sides of the Same Coin

The aging immune system falls apart in a number of different ways, and as the researchers here note, the process probably isn't just one of decline, but of a continual adaptation to that decline. Present nomenclature tends to categorize aspects of immune system aging into broad categories by the type of outcome produced. These are (a) immunosenescence, the weakening of the immune response to pathogens and failure of immune surveillance of potentially dangerous cells, (b) inflammaging, progressively raised levels of chronic inflammation, and (c) autoimmunity, in which the immune system begins to attack tissues. In reality, everything in biochemistry is connected to everything else, and these outcomes are the consequences of interacting, shared processes of decline and damage.

Any successful effort to turn back immune system aging, such as by selectively destroying malfunctioning or unhelpfully configured immune cells, and restoring the generation of new immune cells to youthful levels, should go some way to addressing all of these issues. The researchers here suggest caution on selective reversal of symptoms of immune aging, as some are beneficial adaptations, but in my opinion this shouldn't apply to efforts to address the lower level causes of immune aging. Where adaptations occur, they are adaptations to those causes, an attempt to claw back some functionality in the face of decline. That becomes moot, and the adaptation should cease, if its trigger is removed.

Aging is one of the most intricate and complex biological phenomenon. One physiological system that shows marked changes during aging is the immune system. The interest of the immune system in aging is related to the fact that this is an interacting master regulatory system that keeps the organism free of invaders, either internal or external. Since the introduction of the notion of immunosenescence, many scientists have questioned the justification for unidirectional implication of the immune system and its decreased efficiency associated with aging. Whereas some functions are indeed decreased, others are increased. Therefore; changes are not as uniform as the designation would suggest.

Accordingly, we can propose a new paradigm for dynamic immune changes with aging. We suggest that aging leads to modified/modulated responses of the immune system, making it more adapted to cope with challenges (pathogens) in a given (local) environment, and not just to an eventually terminal deterioration of the immune system. From an evolutionary perspective, this is a simple optimization of the resources of the aging body, even if it ultimately leads to pathologies and death. Immunosenescence may be necessary for an adequate response to known antigens, but detrimental for responses to new antigens in most circumstances. From this perspective, many or most age-related changes in the immune system may be desirable adaptations to the aging process, and thus no need for rejuvenation seems to be necessary.

In conclusion, most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflammaging. Together, immunosenescence and inflammaging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system.

If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflammaging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened.

Link: https://doi.org/10.3389/fimmu.2017.01960