Chronic antigenic load vs Longevity

[Joseph_Lavelle]

Has this idea of life long cumulative antigenic load (reactions to toxins, chemicals, bacteria, viruses) a cause of Inflamaging and reducer of life and healthspan….become a legitimate hypothesis?

“ old people have to cope with a lifelong antigenic burden encompassing several decades of evolutionary unpredicted antigenic exposure. This chronic antigenic stress and the subsequent inflammatory burden have a major impact on survival and frailty. The quality of ageing and the peculiar remodeling of the IS in more advanced age are the results of the individual immunological history, which therefore heavily influences both longevity and successful ageing”

“ The most important characteristic of immunosenescence is the filling of the immunological space with memory and effector cells as a consequence of exposure to a variety of antigens. The continuous attrition caused by clinical and sub-clinical infections, as well as the continuous exposure to other types of antigens (food, allergens), is likely responsible for the chronic IS activation and inflammation”

https://febs.onlinelibrary.wiley.com/doi/10.1016/j.febslet.2005.02.055

[Joseph_Lavelle]

This post is related to my latest post

Leaky Gut — 2023 paper

Excellent review of LGS causes and solutions as currently known. Lots of misunderstandings floating around. Conclusion summarized below. Full paper linked. “Certain infections, an unhealthy diet, stress, excessive use of antibiotics and other drugs, and alcohol can influence increased intestinal permeability and cause leaky gut syndrome. The intestinal hyperpermeability produced in leaky gut syndrome leads to an alteration of the tight junctions, the entry of toxic agents into the blood, and dysfunction in organs and systems. Leaky gut syndrome therapy should include diet modification avoiding fats, sugars, additives, and ultra-processed foods, and the appropriate supplementation of probiotics/prebiotics, arginine, glutamine, polyphenols, vitamins, fibers, medical herbs, edible mushrooms, and FODMAPs.”

[Olafurpall]

I think reduction in immunolotical space due to antigenic load is definitely a factor in aging of the immune system. I have talked about it before here:

Are there immunosenescence risks of excess antigenic burden from getting too many vaccinations/COVID booster shots?

from @Olafurpall You’re right in that the ravages of aging wear out the immune system, but you’re missing the fact that encounter and responses to vaccines and infections is one of those ravages. While you’re correct in that exposure to pathogens in youth leads to development of immunity that is beneficial at older ages, you’re assuming that the body can get exposed to and form immunity against unlimited number of pathogens without any negative effects. This assumption is wrong due to something called immunological space. Every time your immune system encounters an “enemy”, be it from a vaccine or an infection, and it responds appropriately, the body will develop immunity to that enemy. It does this by training memory B-cells and T-cells that recognice the antibodies on the enemy so if you get exposed to it in the future your immune system will respond fast and destroy it before you get significantly ill. This is all good, except that each time your body does this, the new memory ce…

The main question IMO is, how much of a concern is this at different ages and exposure levels? I think this is definitely a concern for old people. For young people, the concern is lower due to them having been exposed to less antigenic stress over their lives so they can wait longer until it starts becoming a problem. This is important because I expect treatments to become available to restore immunological space in the future. I think, relative to many other age-related problems, this one is not so hard to solve. At the same time, solving this would only partially rejuvenate the immune system. There is more to immune aging than reduction in immunological space.

[Virilius]

Since we cannot avoid damaging environmental factors, we need to concentrate on mitigating them.

[Dr.Bart]

I have to make some comment as an immunologist.

#1 The term “antigen” is misused. Antigen has potential to form an immune reaction typically in from of antibody. Antigens are usually biologic in nature, protein, lipoprotein, glycoprotein etc. Chemicals rarely act as antigens on their own are usually called haptens if they lead to immunological reactions.

#2 Antigenic stimulation if done correctly can be beneficial to the body. This why we need probiotics in our gut which for example reduce chances of autoimmune reactions. Controlled exposure to pathogenic antigen can create immunity and prevent future disease. Think of it like exercise for the immune system

#3 Toxins are chemical or biological agents that are… toxic. So damaging in various ways to our bodies. They evoke a non-specific inflammation designed to clean up and repair the damage. Toxicity is usually dose dependent. Small amounts can be therapeutic in many cases…like most of pharmaceuticals.

So bottom line, like most things in life, it’s way more nuanced that it seems.

[Joseph_Lavelle]

Thanks. I think the idea was to not limit the issue to viruses or infectious agents. But it’s good to use proper terminology.

That said, what do you think of the hypothesis that the viral / bacterial/ other stuff “load” over a lifetime is positively correlated with worsening immune function (autoimmunity, clearance of senescent cells, etc)?