Far Too Little Consideration is Given to the Failure of the Immune System in the Old

There is no situation so terrible that it will not be silently accepted as set in stone, only given that it has lasted for long enough to become routine. So it is with aging, and all of the pain, suffering, and death that accompanies it. The present furor surrounding COVID-19 is unusual for casting at least a little light upon the point that infectious disease largely kills older people, and in very large numbers, year in and year out. In the normal course of affairs, no-one cares until it is their turn to be old, frail, and vulnerable.

The immune system decays with age, becoming simultaneously overactive (inflammaging) and incompetent (immunosenescence). It doesn't just fail at the vital tasks of defending against pathogens and destroying cancerous and senescent cells, but also actively contributes to the onset and progression of inflammatory conditions of aging, from cardiovascular disease to dementia. The principal causes of immune aging are easily described: the thymus atrophies with age, slowing the supply of matured T cells to a trickle by age 50; hematopoietic stem cells responsible for creating immune cells become dysfunctional and damaged; lacking reinforcements, immune cell populations become rife with exhausted, senescent, broken and misconfigured cells.

In the commentary I'll point out today, the authors point out that mortality due to fungal infections is a particularly neglected aspect of the age-related decline of the immune system. The cost is high, and far too little attention is given to this issue - just as, in the broader picture, far too little attention is given to the issue of immune aging as a whole, and the enormous cost in suffering and death that it causes. Too few programs are attempting to reverse the causes of immune aging, even though this is a realistic goal, with many proof of concept studies in mice achieving positive results over the past few decades. As a species, we prioritize poorly.

Fungal infections in humans: the silent crisis

Humankind has been plagued by infectious diseases throughout history, and the ongoing COVID-19 pandemic is a daunting reminder that this susceptibility persists in our modern society. After all, communicable diseases remain one of the leading causes of death worldwide. Unfortunately, some of these "microbial threats" have been underestimated and neglected by healthcare authorities, although they endanger millions of lives each year all over the world.

Fungal infections (FIs) represent an example of such overlooked emerging diseases, accounting for approximately 1.7 million deaths annually. To put these numbers in perspective, tuberculosis is reported to cause 1.5 million deaths/year and malaria around 405,000 deaths/year. The medical impact of FIs, however, goes far beyond these devastating death rates: FIs affect more than one billion people each year, of which more than 150 million cases account for severe and life-threatening FIs. Importantly, the number of cases continues to constantly rise. Thus, FIs are increasingly becoming a global health problem that is associated with high morbidity and mortality rates as well as with devastating socioeconomic consequences.

A crucial factor that contributes to the rising number of FIs is the drastic increase of the at-risk population that is specifically vulnerable to FIs, including elderly people, critically ill or immunocompromised patients. The overall lifespan increase due to the achievements of modern medicine and social advancements, the growing numbers of cancer, AIDS, and transplantation patients with the concomitant subscription of immune-modulating drugs as well as the excessive antibiotic use compose risk factors and niches for the development of FIs. Furthermore, the increasing usage of medical devices such as catheters or cardiac valves leads to a higher risk for the formation of biofilms. Biofilms represent an assembly of highly diverse, complex and eminently organized cells embedded in an extracellular matrix that conveys protection from physical and/or chemical insults. Thus, biofilms are often resistant to existing treatments and, in fact, are considered to essentially contribute to the high mortality rates associated with invasive FIs.

There is no doubt that the threat imposed by FIs will continue to increase worldwide with a number of obstacles (including resistance development) that need to be overcome. This demands rapid and innovative action at different levels. The search for therapeutic treatment options needs to be intensified. In sum, FIs are crucial contributors to the new old threat of infectious diseases, and upgrading our antifungal armamentarium by improving existing and/or devising novel antifungal strategies remains an urgent medical challenge.

Comments

The sad state of affairs that the people with the means and energy are the ones that don't immediately care for the effects of aging. Yes they give token tribute to the issue since there are family and acquaintances being affected. There is even the personal observable degradation of health the people see starting as early as late 20s (well there is mostly cosmetic) . Since over the millennia there was nothing that could be done the established expectations is for the old to just curl and die to quickly free the world and don't use the space and resources needed by the younger. In fact, it was frowned on the old people that just don't step aside and still linger around. It doesn't help if the said old people look ugly, cannot hear well, and probably have bad temper and not the sharpest mind.

What is remarkable that socially we mature slower like people in their 30s living with their parents, starting families much later and expected to be in the work force till late 60s. With the medical and technological advances we can even be be able to do it but biologically we are not slowing the aging we just linger longer and cope better with the morbidity. Simple interventions like controlling blood pressure, some exercise , diet do help. But at some point we will need some serious medical help. But even with all the medical advances we can only get at most a couple of decades more in decrepit state compared to somebody getting only basic medical services...

And the deathist attitude is pervasive. A close familiarly member of mine was getting examined to qualify for disability status. And it was openly said that there's no code for aging yet it is normal to be decrepit without a specific condition.

I am surprised that with the advent of senolytics nobody is making big enough waves to wake up the main stream media. Now for the first time in history it is possible, and , in fact, quite easy to address and even reverse some aspects of aging with readily available chemicals. Unfortunately, the effects are not strong and profound enough yet to attract the media attention.

Posted by: cuberat at July 3rd, 2020 6:26 PM

On the other hand, the concept of growing/printing organs falls naturally within our experience with machines. We do constantly repair equipment and replace broken parts. The biggest attention (and money) goes to the possibility to heart and kidney transplants since those are the most shockingly miraculous. But much smaller tissues still can be useful. Probably more useful on aggregate adjusted health-years that can be achieved.

Posted by: cuberat at July 3rd, 2020 6:28 PM

Now finished phase 111 and in application for licensing is a mesenchymal stem cell approach to bone marrow transplants (which are a bit of a dead loss at present as perfect tissue matches are almost impossible)
Essentially, one would be replacing the existing immune system, either completely or partially, with a fresh, new, young one.
The aim is to cure leukaemia but no conceptual reason why this approach could not also be used for ageing.

Posted by: JLH at July 4th, 2020 6:38 AM

Reason,
How much progress has Repair Biotechnologies made with their Thymic Rejuvenation research?

Posted by: Trevor Bingley at July 5th, 2020 6:01 PM

Yea, I'd be curious how you are doing with your company, Reason. I hope very much you're making significant progress in the last couple years of your biotech company.

I read in today's Mercury News on the front page(San Jose, Ca.), someone from the Buck Institute (sorry, don't recall his name), talking about the diminishing ability of the immunity system as we get older. As I recall, SENS is located in nearby Mountain view, BTW. This person is 63 years and talks about eating right, getting enough sleep, exercise, the standard stuff to be as healthy as possible. He was talking about why the virus more fatally affects older people compared to younger counterparts.

Posted by: Robert at July 5th, 2020 8:01 PM

I don't think there will be updates on Repair Biotechnologies just on request. Even though it is a private company news and press releases probably still need to be carefully released.

Getting a gene therapy into the thymus is difficult problem due to it's location. I'd be interested to learn what targeting technology Repair Bio is planning to use, but I am prepared to wait to hear this.

https://www.youtube.com/watch?v=rnfmIkvsDoQ

Posted by: jimofoz at July 6th, 2020 5:58 AM

Regarding Repair Biotechnologies, that is about right; one can't talk as openly as one would like.

Posted by: Reason at July 6th, 2020 1:37 PM

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