One would hope that it does not require an ongoing pandemic and related hysteria to point out that old people have poorly functioning immune systems, and thus suffer disproportionately the burden of infectious disease. But perhaps it does. The 2017-2018 seasonal influenza, a modestly more severe occurrence of something that happens every year, killed something like 60,000 people in the US alone, with little notice or comment. There is nothing so terrible that it won't be accepted - ignored, even - if it is normal.

Floodgates of funding for infectious disease research and development have been opened in response to COVID-19, and while no doubt all too little of it will be spent wisely or usefully (public funding being the very definition of waste and corruption) it has certainly prompted many groups to try to position themselves to benefit. Those who have, all along, been working on ways to try to make older people more resilient via improvement in their immune function are perhaps more deserving than others, but it really isn't the case that much of this work is closer than five to ten years away from practical realization and completed human trials.

Of the ways to restore immune function in the old, the worst are the small molecule drugs that show signs of adjusting metabolism in the right direction. For example, the mTOR inhibitors that just failed a phase III trial for reducing influenza incidence in the old. Better drug or drug-like approaches are those that target regrowth of the atrophied thymus. The thymus is where T cells of the adaptive immune system mature, and the production rate is reduced to a trickle in the old - a major cause of immune aging. In humans, there is data for the growth hormone approach of Intervene Immune, and better data for sex steroid ablation, to restore the production of T cells.

Further, regeneration of lymph nodes, vital to coordination of an immune response, and regeneration of the hematopoietic stem cell population that creates all immune cells will be beneficial - but existing approaches to these challenges are by no means close to readiness for clinical trials. Selective destruction of malfunctioning, senescent, and exhausted immune cells is also likely to be beneficial - but only removal of senescent cells via senolytic therapies is a very near term prospect at the present.

At the end of the day, therapies capable of making a 70 year old exhibit the immune profile and response of a 40 year old would be transformative. The world has come to accept that sizable numbers of older people die from infectious disease every year, and that this is set in stone and little can be done about it. That is simply not the case - a great deal can be done about it. It just requires the will and funding to move ahead with the most plausible programs of immune rejuvenation.

It is worth noting that the pandemic statistics referenced in today's open access paper require some interpretation and none should be taken either at face value or as usefully applicable across the board. Context is everything. Testing for COVID-19 is presently very selective for symptomatic, more severe cases. No-one yet has a good grasp on how many mild cases there are, and that is everything for determining actual mortality risk. Further, circumstances such as an enclosed cruise liner are not representative of the way matters progress in the broader population. And so on.

Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections