Immunosenescence is both functional/adaptive and dysfunctional/maladaptive

Abstract

Alterations in the immune system with aging are considered to underlie many age-related diseases. However, many elderly individuals remain healthy until even a very advanced age. There is also an increase in numbers of centenarians and their apparent fitness. We should therefore change our unilaterally detrimental consideration of age-related immune changes. Recent data taking into consideration the immunobiography concept may allow for meaningful distinctions among various aging trajectories. This implies that the aging immune system has a homeodynamic characteristic balanced between adaptive and maladaptive aspects. The survival and health of an individual depends from the equilibrium of this balance. In this article, we highlight which parts of the aging of the immune system may be considered adaptive in contrast to those that may be maladaptive.

The dual role of the immune system in the course of COVID-19. The fatal impact of the aging immune system

“…Thus, there is a question to what extent we should intervene to “normalize” immunosenescence and inflammaging. Yes, we should intervene carefully [ 72 ], as both inflammaging and immunosenescence are in part not a process of deterioration, but of adaptation [ 73 ] to the age-associated changes occurring not only in the immune system itself, but also in the other parts of the aging organism as well.…”

“…Interestingly, extremely old persons (centenarians), who are by no means free from chronic inflammatory diseases and cancer, tend to have vigorous inflammatory responses which manifest not only as high proinflammatory cytokine levels, but also high CRP values. Again, their relatively good health and likely, in fact sometimes observed, good survival rate after SARS-CoV-2 infection, seems to be in part the ability to fight the virus itself, but in part also the ability to maintain the balance between pro- and anti-inflammatory mediators, which is typical for these oldest individuals [ 73 , 76 ], the bearers of a “beneficial genome”.…”

Aging versus youth: Endocrine aspects of vulnerability for COVID-19

“…Together with the cellular aging, unfavorable aging-related immune system changes, termed as “immunosenescence” seems to be at the bottom of various age-related chronic diseases and the vulnerability to acute clinical conditions, particularly infections. On the other side, this remodeling occurs due to the struggle of the organism to maintain the homeostasis and adaptation to environmental stressors [ 13 ]. It is shaped under interactions of multiple intrinsic factors including genetics, sex hormones, insulin resistance, and adiposity [ 14 ] and various acute and chronic extrinsic or intrinsic factors might accelerate or decelerate its progression [ 15 ].…”

The complex relationship between Immunosenescence and Inflammaging: Special issue on the New Biomedical Perspectives

“…A variety of molecules, such as stress hormones, mitokines, DAMPs, and garbage accumulation (garbaging), are able to modulate the acceleration or the deceleration of aging process loading on the inflammaging tone [7]. Immunosenescence (and inflammaging) have usually a negative connotation, but, according to a variety of recent observations, the changes of the immune system with age are much more complex, personalized, and dynamic than previously thought, being characterized by homeodynamic features balanced between "adaptive" and "maladaptive aspects" (discussed by [8] in this issue).…”

“…Within such a complex scenario, recent advances in systems biology, integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly (See [8,16,24] in this issue). In particular, motivated by the still unclear immunopathological mechanisms of SARS-CoV-2 infection, Ciabattini et al stress that the design of vaccination strategies for older people is extremely challenging.…”