Posted on 2 June 2022
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Gene therapy opens up a vast area of new opportunities for treating all kinds of diseases, including ageing itself. Scientists rightfully proceed very cautiously when it comes to testing gene therapies in humans, since this can involve making long-lasting or permanent modifications to the genetic code. For a gene therapy to be approved for clinical trials in humans, the benefits usually need to clearly and significantly outweigh the risks, which usually means targeting severe diseases with well known and specific genetic causes.
Self-experimentation by scientists removes many of the ethical concerns involved in exploring new treatments and can give us a better idea about whether they are safe, paving the way for more thorough clinical trials in the future.
What did the researchers do: In this study, which began in 2014, researcher Brian Hanley conducted a self-experiment in order to investigate the effects of using gene therapy to boost their levels of a molecule similar to GHRH (growth hormone releasing hormone). GHRH was chosen because it had been shown to have beneficial effects on various health metrics, including cognition, and because this kind of gene therapy had been shown to be safe in animals, even when it resulted in GHRH being 25-50 times higher than normal levels.
The experiment was designed by Hanley, who was in his late 50s at the time, and was carried out by injecting plasmids (circular pieces of DNA) containing the relevant genetic material into each thigh. A technique called electroporation was then used to complete the gene therapy – this involves delivering pulses of electricity to the tissue, which helps the plasmids to enter the recipient’s cells. No anaesthetic was used for the first set of injections in 2014. This was reportedly more painful than anticipated, eliciting the remark ”on a POW that would be a war crime,” so anaesthetic was used for the second set in 2016, which alleviated the discomfort.
Over the subsequent 5 years, blood samples were taken and various markers of ageing including telomere shortening were measured.
Key takeaway(s) from this research: By the end of the study, the extent of telomere shortening, which is thought to be a driver of ageing, was not significantly different from what would have been expected. However, epigenetic age (a marker of ageing based on small modifications to the DNA molecule that occur naturally throughout life) was reduced by about 6 years. The effect on phenotypic age (a measure of biological age that can tell you if you are physiologically younger or older than your chronological age) was much stronger, with a mean decrease in 28.6 years compared to what it was before the treatment.
Other apparent benefits were also measured, including an improvement in cholesterol balance, an increase in testosterone levels that remained within the normal range, and self-reported faster healing from sports injuries.
It’s not possible to say, based on these results, whether the treatment will increase Hanley’s lifespan. Co-authors of the study suggest that the reduction in epigenetic and phenotypic ageing, but without a significant change in telomere length, is more likely to indicate an increase in healthspan (number of years spent free of chronic diseases of ageing) without an increase in lifespan, which is still a very desirable result.
With a sample size of one, we’ll never know with certainty whether the observed changes were due to the gene therapy, something else Hanley did, or even due to chance (though for some measurements this seems unlikely). The most striking finding was that phenotypic age was reduced by 26.8 years, even after the calculations used to estimate this number were adjusted to give a more conservative estimate. It’s worth keeping in mind that Hanley was already in good physical shape at the start of the study, cycling two days a week and lifting weights 3 days a week.
Results of a 5-Year N-of-1 Growth Hormone Releasing Hormone Gene Therapy Experiment: https://www.gwern.net/docs/longevity/senolytic/2021-hanley.pdf