Fight Aging!

This post reports on the outcome of a self-experiment with three of the Khavinson peptides (epitalon, thymogen, and vilon) and the supplement melatonin in an attempt to produce thymic regrowth. There is evidence in animals for some of these peptides to produce thymic regrowth, as well as evidence for some of these peptides (thymogen particularly) to reduce mortality in old human patients. All of this comes from the Russian research community, however, and original sources are not all that accessible. Certainly, no-one has checked to see whether the thymus is regrown in humans following treatment with these peptides.

Thymic regrowth is a desirable goal, a way to restore immune function in older people who have lost some, most, or all of the active thymic tissue needed for the production of naive T cells. The loss of this supply of new T cells is an important component in the age-related decline of the immune system. Thus it seems worth the effort to gather data on this front. Last year I posted a study outline for a self-experiment with Khavinson peptides, and this year I have a report from one adventurous self-experimenter, using a more aggressive version of that study protocol.

Study Outline

Based on the published outline, this was a nine-month study. On each of the first ten days of every month, a mix of 10mg epitalon, 10mg thymogen, and 10mg vilon in was injected subcutaneously. This was split between two injections 12 hours apart, morning and evening.

This study included the use of a high dose (20mg daily) of melatonin in addition to Khavinson peptides, on the basis that there is good safety data for melatonin, and a single study has shown an increase in thymic tissue resulting from supplementation with melatonin at the equivalent dose in mice. This is an entirely speculative addition, but years of data on melatonin use suggests no meaningful downside at this dose. The 20mg of melatonin were taken orally in the evening, which differs from the mouse study, in which melatonin was supplied in drinking water.

A CT scan of the thymus was taken before and after the study. A complete blood count assay was used to assess lymphocyte:monocyte ratio before and after the study. That is a number that becomes lower with age, and which should increase if the thymus is more rather than less active. Ideally an assay to measure recent thymic emigrants would have been included, but was not. Recent thymic emigrants are T cells recently emerged from the thymus, within the past few weeks.

Subject Details

The subject for the self-experiment was in the 45-55 age range, healthy and without chronic conditions, with a BMI of ~22 throughout the duration of the experiment. Diet and exercise were described as "relatively consistent" across the study duration. I feel that one should always be relatively skeptical of that sort of claim, however, no matter how formal or informal the study.

Results

CT images of the thymus showed a visible reduction in active tissue across the nine months of the study, the opposite of the hoped outcome. In the image below, paired cross-sections through the chest are shown, before on the left, after on the right. For guidance on reading CT scans of the thymus, refer to "Normal Thymus in Adults: Appearance on CT and Associations with Age, Sex, BMI and Smoking". In a cross-section of the chest, as below, and as in the examples given in that paper, the thymus is the triangular patchy grey structure closer to the top of the image, immediately below the sternum (white). Areas of fat will appear dark in the range chosen here, and thus a more atrophied thymus, in which more active tissue is replaced with fat, will appear darker. By late life, the thymus is entirely dark, fatty.

There was no meaningful change in lymphocyte:monocyte ratio. Over four years of complete blood count data prior to this study, leukocyte:monocyte ratio varied from 4.4 to 6.5, with no particular trend. In three measures after the study, leukocyte:monocyte ratio was 5.8, 6.0, and 4.0.

Conclusion

Use of the Khavinson peptides and melatonin in combination in this way, at this dose, negatively impacts the thymus, producing a reduction in active tissue and increase in atrophy to fatty tissue. The degree to which this atrophy occurred is greater than one would expect to take place over nine months of aging at this stage of life.

Why did this outcome occur, given the animal studies showing thymic regrowth, and the studies showing reduced later life mortality following use of thymogen? We can only speculate. Firstly, the dose makes the poison, and the dosing here may have been too high, too frequent. In one of the human studies, testing thymogen only, dosing for ten days occurred only one every six months, rather than monthly as here. Secondly, it may be that these peptides are pleiotropic in their effect on the thymus, and only beneficial after the thymus is very atrophied. Thirdly, it may be that in humans any benefit to the use of Khavinson peptides arises from increased peripheral T cell replication in useful populations, such as naive T cells. This could be beneficial on balance in late life, allowing greater resistance to infection, even if it pushes the patient further towards the accumulation of senescent and exhausted T cells. Lastly, the existing study data for Khavinson peptides relevant to this exercise may simply be dubious, wrong, or otherwise bad.