Towards Better Vaccines and a Lower Burden of Infectious Disease in Old People

Over a lifetime, the burden of infectious disease - and particularly persistent infections such as cytomegalovirus - influences the pace of aging via its detrimental impact on immune function in later life. The slow upward trend in life expectancy over the past two centuries is due in no small part to reductions in infectious disease that accompanied improvements in sanitation and then medicine. In addition, in old age, once the immune system declines into ineffectieness, infectious disease becomes a much more serious concern. Infections that a young person defeats with ease become life-threatening. The primary strategy to address this issue presently adopted by the research community is to expand and improve on vaccines for older people, as the authors of today's open access paper outline. The issue with this approach is that the aged immune system is ineffective, and thus while there are some techniques that can improve vaccine performance, that performance is always going to be poor.

If we want older people to exhibit a much lower burden of infectious disease, and to respond well to vaccines, the only viable way forward is to rejuvenate the immune system. Forms of therapy that might achieve this goal include regrowth of the thymus, the organ responsible for the maturation of T cells of the adaptive immune system, and which atrophies near entirely by age 50 or so. Additionally, damaged and dysfunctional hematopoietic stem cell populations of the bone marrow must be restored to a youthful capacity to generate immune cells. Further, growing populations of exhausted, senescent, and misconfigured immune cells must be selectively destroyed. Development of each of these approaches is a major undertaking, even given that meaningful inroads have been made towards a basis for therapies.

Preventing infectious diseases for healthy ageing: The VITAL public-private partnership project

People at an older age mainly die of three causes, accounting for 85% of them: cardiovascular disease, cancer, and respiratory system diseases. Although infection constitutes only a secondary cause of death in that group, happening mainly during the winter periods because of influenza infection and pneumonia disease, it is a major threat for aging adults in cluster environments like rest homes or health care facilities. People from that age group arriving in hospitals with a secondary diagnosis of infection monopolize the beds for a long period, recover badly and remain weak when leaving the health care facility. This results in a long-term poor overall health condition with a high cost for society.

Healthcare systems will have to deal with increasing numbers of ageing adults with severe infections, not only because of the higher number of individuals living longer but also because of the decline in their immune response, called immunosenescence, which makes them more vulnerable to pathogens. Ageing adults may thereby also become a new source of infection. However, an effective medical act to safeguard individuals and populations against infectious diseases is vaccination, which has proven its effectiveness in children and young adults. The ambition is to achieve a similar level of infectious disease control in ageing adults. This would be fundamental for enhancing healthy ageing. However, many recommended vaccines for ageing adults do not maintain an effective and/or sustained immune response, as is the case for influenza, pneumococcal disease or pertussis, for example.

Therefore, there is a need to better understand the aetiology of the major infectious diseases affecting this population. There is also a need to decipher the mechanisms underlying immunosenescence, which should lead to improved vaccine effectiveness and to the development of more efficient vaccination strategies for this age group (whom to vaccinate, when, where, how frequently, and at what price). Finally, there is a need to provide dedicated educational programs to healthcare professionals. Over the next decade, local decision makers will need to have a clear view on this healthcare problem, with access to effective tools to manage the growing healthcare burden they need to control.

Comments

"People at an older age mainly die of three causes, accounting for 85% of them: cardiovascular disease, cancer, and respiratory system diseases"
Not only is immune system decline a culprit in much of this, but also hormone deficiencies. In fact, recent studies are showing that heart failure can be reversed with growth and sex hormone supplementation (which we also now know can improve immune function):
"Combined effects of GH and TRT in heart failure" 2019
https://pubmed.ncbi.nlm.nih.gov/31696666/
"Anabolic deficiencies in Heart Failure: Ready for Prime Time?" 2020
https://pubmed.ncbi.nlm.nih.gov/31735309/
This again makes me question the emphasis on restricting metabolism/anabolism as a tactic for life extension in aging humans. Rather, we should determine levels that optimize health and longevity on a case by case basis (i.e., GH/HR/TRT are not "good" or "bad"; it depends on dosage and patient status). imho

Posted by: dtkamp at August 17th, 2020 5:29 PM

The TRIIM studies are going to have to account for the fact that bone marrow stem cells are not as available when measuring any level of success in thymus regeneration. Why not combine a replenishment of these cells (if that's even possible) with the thymus regeneration effort?

Posted by: Nathan at August 18th, 2020 9:22 AM

The rejuvination of skin cells with the use of fractionated pulsed laser modalities is a well established science. Beyond the use of peptides to rejuvinate the thymus does the editor consider the use of lasers to be use in the restablishment of a healthy immune system ( reversing the involution of a thymus) ?

Posted by: Daniel Craver at August 23rd, 2020 4:34 AM

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