Thymic Involution and the Decline of the Immune System with Age

Thymocytes created in the bone marrow travel to the thymus, and there mature into T cells of the adaptive immune system. The thymus, unfortunately, atrophies with age, a process known as thymic involution. By age 50 it is largely fat tissue, and the supply of new T cells diminishes to a trickle. In old age, the total number of T cells remains much the same as in youth, but absent regular reinforcements, all too many of these vital cells are worn, damaged, exhausted, senescent, and often pathologically misconfigured. Too few competent T cells remain to carry out the vital tasks of killing pathogens and errant, potentially cancerous cells. This is a major cause of immune system aging and the frailty and vulnerability that follows.

The thymus, which exists in nearly all vertebrates, is a primary lymphoid organ essential for the maturation of bone marrow (BM)-derived T lymphoid precursors. The maturation and selection processes of T cells in the thymus generate a pool of circulating naïve CD4 and CD8 T cells. Such a pool allows the generation of immunity, on the one hand, and the ability to maintain tolerance to self-antigens, on the other hand. A proper thymic output may thus be considered a crucial first stage that generates a highly diverse T-cell repertoire, which is required to maintain plasticity, protection, and repair, while minimizing the risk of pathogenic autoimmunity. Since CD4 T cells evolved to play a key role in orchestrating these functions, they may be considered keystone in the ecosystem of properly regulated immunity.

Regardless of the seemingly crucial role of the thymus in preserving homeostasis, its involution begins in childhood and peaks up around puberty, resulting in an almost completely non-functional organ in aging. Thymus involution gradually reduces the output of naïve T cells with age. Dynamic changes in the thymic T lymphocytes include a reduced number of undifferentiated T cells and an increase in terminally differentiated cells (e.g., T cells with memory phenotypes). A hint to the effect of thymus involution can be found in the context of early life (before puberty) thymectomy. In young humans, thymectomy results in T-cell changes that are similar to those related to immunosenescence. Specifically, it was shown that the number of both CD4 and CD8 naïve T cells decreases while the number of memory and exhausted phenotypes increases.

These studies may imply a causal link between thymus involution and accumulating defects in the immune system with aging. The overall process that leads to immune failure in old age is apparently the sum of parallel processes, namely, thymus involution, intrinsic T-cell defects, chronic inflammation, and cell senescence. Targeting these components may shed light on the impact of each process and its therapeutic potential for the restoration of immunity and its repair in elderly.



On a related note to immune system rejuvenation, Kimer Med is now crowdfunding the development of a broad-spectrum antiviral that is a variant of the DRACO research from a few years ago. Their goal is $50,000 (NZ) and they only have $8,707 with 6 days left in their campaign. Even $10,000 will allow some additional testing. Please help and tell others:

Posted by: Morpheus at December 7th, 2020 12:01 PM

I've been interested in Greg Fahy et al TRIIM study on thymic restoration, immune (enhancement) and insulin mitigation.

For a recap for those unfamiliar with the study, he administered his subjects with:
- human growth hormone
- metformin
- zinc, and
- vitamin D

I understand the issues regarding human growth hormone not being easily bioavailable. However, about a year ago, I adopted Blood Flow Restriction with Low Load resistance training to rehabilitate an injury; and one of the measured effects of such is increased hGH (among other benefits).

Since Metformin is only available by prescription in the US, I have substituted berberine a supplement with similar properties.

The other components of the study I incorporate, as indicated.

I don't have any before or after data, however, I did have a fairly comprehensive blood, physical and dna panel and my results were good. My telomere length was greater than expected for my age (greater than 1 standard deviation above chronological age cohort).

For an old guy, I have pretty decent physical fitness (could 'ace' the Navy physical fitness test: 100 push ups and 100 crunches) and cardiovascular health (ran 4.6 mi in 45 min, today) and body fat 14%.

I seem to have seen a lot of interest in Fahy's protocol, however, not seen anyone suggesting physical exercise (incl with BFR) as a means of upping HGH.

Posted by: TB at February 12th, 2023 5:45 PM
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