In September 2019 Fahy et al. published results from the TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation) trial. Their stated goals were to investigate whether they could restore the immune systems in eight healthy older men (ages 51 - 65) using a combination of recombinant human growth hormone, dehydroepiandrosterone and metformin. While they achieved impressive on-paper results partially restoring the thymus, the most impressive result came from their epigenetic measurement of aging of subjects in the trial.
Fahy et al. had successfully reversed aging in their subjects according to four epigenetic measures of aging. The effect size was large: each measure indicated an average gain of over 2 years after 1 year of treatment.
In other words, if hypothetically a subject was 60 years old at the beginning of the trial, both chronologically and epigenetically, then by the end of the year they would be 61 years old chronologically but less than 59 years old epigenetically.
Of the epigenetic measures of aging, GrimAge is thought to be the best available predictor of lifespan. From the paper introducing GrimAge,
Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death, time-to-coronary heart disease, time-to-cancer, its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause.
Fahy et al. demonstrated a mean age reversal of 2.16 years after 1 year of treatment according to the GrimAge measurement (see Table 1 in the paper).
Fahy is reportedly spearheading a new trial, called TRIIM-X (see this part of his recent TEDx talk). He hopes to investigate the effects of a modified version of the same treatment with the benefits of a larger trial and a more diverse set of participants.
The skeptical side of me has a question:
- Is a reversal of the epigenetic clock good evidence that aging was reversed, or is there a good theoretical reason to think that you can reverse the epigenetic clock without reversing “true” aging and thus increasing lifespan?