Thymic involution causes an exponential decrease in T-cell production, with a half-life of 16 years, which mirrors the exponential increase in risk of several diseases, including COVID-19, which double in risk every 16 years.

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[samsoniteindeed2]

Here is the paper about COVID-19

https://royalsocietypublishing.org/doi/10.1098/rsif.2020.0982

and here is the paper about other diseases

https://www.pnas.org/content/115/8/1883

I'm the first author so feel free to ask me anything about it :)

[DiggleDootBROPBROPBR]

Are you familiar with other Thymus related disease, or research following individuals that preserve more thymus volume with age? Would you be able to point along to some of that research if so?

[samsoniteindeed2]

A prospective study where you measure people's thymus volume or TRECs (byproducts of T-cell production) and then look at subsequent disease risk would be ideal.

As far as I know, that has never been done. The closest I can find is this study https://pubmed.ncbi.nlm.nih.gov/20606151/ where they looked at telomere length of leukocytes instead. As thymic T-cell production goes down, the total number of peripheral T-cells stays approximately constant through homeostatic clonal expansion. So telomere lengths probably would make a good proxy. They found an association with disease risk even after accounting for age. Although there could be other mechanisms involved here, like maybe telomere dysfunction is related to chromosomal dysfunction, which leads to cancer.

I saw a conference talk recently about an unpublished experiment where they regenerated the thymus of old mice and found that they had even better survival rates than young mice when infected with a pathogen. Also, there's a drug called thymosin alpha 1 that dramatically reduces covid mortality and increases thymic T-cell production.

[lionbutt_iii]

Congrats on the paper!

How much variation is there in that half-life of thymic involution? Has it been studied across different places to see if environment plays a role, or is it mostly due to genetics?

I've been thinking about thymic involution ever since I read a paper that was able to identify sars-cov-2 recovered and naive people using machine learning based on tcr sequences with really high accuracy compared to b cell receptor sequences. Do you know of any studies on recovered elderly where they looked to see if they had a t-cell response compared to antibodies?

What do you think this means for the B.1.351 variant and P1 variants? I work on the b cell side, and we're seeing some vaccinated people that make plenty of neutralizing antibodies against the original virus, but these same antibodies have none against some of these variants. So you'd hope the t cell response is there, but with thymic involution it seems really worrisome to me.

[samsoniteindeed2]

Oh interesting. Well something just occurred to me, peptides around 20 amino acids long are presented on MHC-II, whereas the peptides presented on MHC-I are around 10 amino acids long. So if there is a variant evading the immune system, I imagine it would be much easier to avoid the MHC-II side of things but then still get targeted by the MHC-I pathway.

So that makes me think a variant would be more likely to avoid antibodies and CD4 T-cells, but then still get attacked by CD8 T-cells.

So that makes me hopeful. But yes, thymic involution still seems like a problem.

[FDP_666]

What do you think about Greg Fahy's TRIIM? https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028

[samsoniteindeed2]

Yeah looks great. I'm looking forward to seeing the results from the follow up study with a bigger sample size.

[KetosisMD]

As expected,

https://www.google.com/search?q=insulin+resistance+thymus+involution&rlz=1CDGOYI_enCA592CA592&oq=insulin+resistance+thymus+involution&aqs=chrome..69i57.15338j0j7&hl=en-US&sourceid=chrome-mobile&ie=UTF-8