Thymus Involution, I recently came across a few papers in the thymus regeneration category. Namely, When the Damage Is Done: Injury and Repair in Thymus Function by Sinéad Kinsella1 and Jarrod A. Dudakov

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01745/full

Interestingly, many of the pathways specifically target TECs to mediate regeneration. FOXN1 upregulation shown to regenerate the thymus. However, they do not mention... during senescence, Wnt4 expression is down-regulated (unlike their Frizzled receptors), while PPARgamma expression increases in the thymus. There may be several microRNA that upregulate FOXN1 or have thymic action.

Interleukin-22 - IL-22 also (along with thymus) has a major role in the regeneration of epithelial cells in a diverse range of tissues including gut, lung, skin, breast, and kidney. It has a key role in driving thymic regeneration after injury, by acting directly on TECs to induce survival and proliferation, potentially via regulation of Foxn1 expression.

Several other methods mentioned.

In relation to hormones...

As for the HGH - DHEA - Metformin.

Castrated men and women show less involution leading to testosterone as contributing to involution. Interestingly, administration of the appetite stimulating hormone Ghrelin led to improved thymic cellularity and thymic output in aged mice. (Ghrelin stimulates growth hormone) a product like MK-677 also being a Ghrelin agonist or selective, and non-peptide agonist of the ghrelin receptor. Perhaps an easy way to see is scans of people with GH acromegaly have less thymus involution with age vs GH deficient.

I am still wondering on mTOR or autophagy caused by metformin as playing a role, rather than metformin as IGF-1 suppression and no other role. Going catabolic fasting towards autophagy activates tissue remodelling and bodybuilding the androgens promote remodelling.

Another interesting SARM is Osterine for Sarcopenia and Oesteoporosis

Finally, KRG Korean Red Ginseng significantly inhibited thymic involution in old mice.

papers below

Korean Red Ginseng Plays An Anti-Aging Role by Modulating Expression of Aging-Related Genes and Immune Cell Subsets

https://pubmed.ncbi.nlm.nih.gov/32218338/

MicroRNAs Regulate Thymic Epithelium in Age-Related Thymic Involution via Down- or Upregulation of Transcription Factors

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684555/

Transgenic Exosomes for Thymus Regeneration

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499203/

Regeneration of the aged thymus by a single transcription factor

https://dev.biologists.org/content/141/8/1627

Damage Is Done: Injury and Repair in Thymus Function by Sinéad Kinsella1 and Jarrod A. Dudakov

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01745/full