Fight Aging!

In the same way that the regenerative medicine field cannot evade addressing the aging of stem cells, the vaccination research community cannot evade addressing the aging of the immune system. The reasons are much the same in both case: all too many of the patients are elderly, and due to the processes of aging, treatments do not work anywhere near as well in older people. Thus effective clinical applications of research will eventually require the relevant effects of aging to be in some way addressed: mitigated or reversed. This is widely understood in the research community. At the present time this understanding largely manifests as efforts to better understand the mechanisms involved. These research communities are large, however, and that means that there are at least a few groups at any point in time whose members are somewhere in the process of moving potential approaches to stem cell or immune system rejuvenation closer towards the clinic.

Vaccines represent one of the most powerful medical interventions against infectious diseases. Effective adult vaccination programs targeting all age groups, including older adults are now more urgent than ever. Changing demographics and the vast increase of aged individuals, necessitates development of efficacious and safe vaccines, suitable for adults and in particular for older adults. While vaccines targeting older populations exist, their performance is often sub-optimal and/or they are under-used. At present, major gaps exist in our knowledge of the mechanisms behind the reduced ability of the aging immune system to respond appropriately to both infections and vaccinations. This hinders our ability to design interventions capable of improving the immune response in older adults and to tailor vaccines better suited for this group.

Aging is characterized by multifaceted changes in the immune system which lead to a progressive reduction of the ability to mount effective antibody and cellular responses against infections and to vaccinations. This phenomenon, referred to as immunosenescence, is multifactorial: it affects both arms of the immune system and can be influenced by genetic factors and extrinsic factors, such as nutrition, physical exercise, co-morbidities, physical and mental stress, previous exposure to microorganisms, toxins, and pharmacological treatments. Consequently, the presenting forms of immunosenescence are protean, varying at population and individual levels.

Therefore the concept of "Bioage" is arising to describe the concept that the real age is not the chronological, but the biological one. The concept of "bio-age" is in line with the observation of the wide variability of immune responses observed in the elderly after vaccination. In addition, it is in line with the increasing evidence that the immunological experience that individuals have during their lives can shape their ability to respond to external stimuli, such as infections or vaccinations. The pro-inflammatory environment of the aging body is a common denominator of aging which is referred to as "inflammaging". Extensive scientific literature has been published on this area and among the many hypothetical potential causes, the most popular is infection with cytomegalovirus (CMV). Indeed, strong CMV seropositivity has been associated with lower antibody and cellular responses to a variety of vaccines. The long-term maintenance of vaccine-specific antibodies seems to be hampered by CMV.

Considering the pleiotropic nature of immunosenescence and its variable expression among older individuals, it is not surprising that, despite the "physiological" decay of the immune responsiveness with age, vaccination remains a vital intervention in the older adults. Several pharmacoeconomic studies have underlined the benefit of influenza vaccines in terms of lives saved and reduced direct and societal costs linked to reducing influenza-related morbidity and mortality. Moreover, failure to vaccinate is associated with excess mortality due to infection and its complications. However, some vaccines have been shown to exhibit sub-optimal efficacy in recipients of advanced age or significant frailty. Differences in bio-age, immunobiography, and trained immunity can reconcile the apparent discrepancy between the reduced response of the elderly to some existing vaccines, and the evident successes that have been obtained recently. There is reason to believe that we can improve on the former by deciphering the mechanisms underlying the latter.

Link: https://doi.org/10.1038/s41514-017-0020-0