A cocktail of drugs — including a growth hormone and two diabetes medications — may be able to reverse the so-called ‘epigenetic clock’, a measure of biological age, according to results of a small trial published on 5 September in Aging Cell, a peer-reviewed scientific journal and an official journal of the Anatomical Society (1).
The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial was led by immunologist Dr Gregory Fahy and begin in 2015 at Stanford Medical Center in Palo Alto, California, just a few months after receiving trial approval from the US Food and Drug Administration.
What is the epigenetic clock?
Epigenetics are heritable changes in gene expression rather than changes to the underlying DNA structure itself. Whereas changes in DNA sequences can take millions of years to appear, epigenetic changes happen much faster and can occur throughout a person’s life.
When DNA is passed along to the next generation of cells, the epigenetic information is passed along too, which can dictate the environmental conditions for which a particular gene is activated. In other words, the environment can have an impact on how DNA is read and which proteins are produced. And this can have both positive and negative repercussions.
The pattern of tag changes that occur during the course of life is referred to as the epigenetic clock, which is an indication of a person’s biological age and can lag behind or exceed chronological age.
Turning back time
Previous studies in animals and human cells showed that a particular growth hormone stimulates regeneration of the thymus, a gland located between the lungs and the breastbone. The thymes is critical for efficient immune function, and therefore, contributes to fighting infection, cancer, and other diseases. However, after puberty, the thymus gland gets smaller and can become congested with fat.
So, the scientists wanted to find out whether the growth hormone could be used to regenerate the thymus gland in humans. Since the hormone is also known to promote diabetes, they added two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin, into the mix. Nine white men between the ages of 51 and 65 years were given the cocktail of drugs for one year. Then, the scientists used magnetic resonance imaging (MRI) to examine changes in the thymus before and after the study and took blood samples throughout the trial.
Amazingly, the epigenetic clock was reversed by 2.5 years on average and the immune systems of the participants improved. In all volunteers, the blood-cell count was rejuvenated. In seven of the nine participants, regenerated thymus tissue had replaced accumulated fat. And the effects persisted six months after the trial, based on six participants who provided follow-up blood samples provided by six volunteers.
The results were surprising even to the scientists involved in the study. “I’d expected to see slowing down of the clock, but not a reversal”, geneticist Dr Steve Horvath at the University of California, Los Angeles told Nature.
Although promising, the results are somewhat limited by the small study size — only nine volunteers — and the trial did not include a control arm. Therefore, further research is still needed. Nonetheless, the findings could have huge implications on healthcare, in general, and perhaps, impacts on how age-related diseases are treated in the future.
(1) Fahy, G.M. et al. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell (2019). DOI: 10.1111/acel.13028