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Agehacking: Can Age Be Reversed?

It is well-known that some people appear to age faster - and some slower - than others. We’ve all met the 40-something that doesn’t look a shade over 30, and takes great pleasure of being reminded of that. It is also well-known that certain unhealthy habits can accelerate the aging process. Your uncle who’s a lifelong smoker and looks 15 years older than he should, thin skin, tired, wrinkly face and hands. We know, at least intellectually, that we can evade this fate by avoiding smoking. We also know that to age healthily our doctor encourages us to cover the basics: eat well, exercise regularly, get enough sleep, don’t drink too much, don’t smoke. In fact, each of these recommendations are backed by solid evidence, and each plays a role in the speed at which your biological clock ticks. (For a quick recap on the difference between chronological and biological age click here.)


But what if I told you that instead of slowing down the hands of our biological clock, we could actually turn them back? What if I told you, “there's a pill for that!”?


In 2015, the immunologist Dr Gregory Fahy set out to answer whether growth hormone could give the immune system a boost by giving the thymus gland a reboot. The thymus is located between your lungs, and under your sternum. Before birth, and through childhood, white blood cells produced in your bone marrow mature into T-lymphocytes (the ‘T’ is short for thymus), or T-cells, in your thymus. A quick immunology refresher: there are Helper T-cells and Killer T-Cells. Helper T-Cells stimulate B-cells to make pathogen-specific antibodies, and help Killer T-cells develop. Killer T-cells are responsible for detecting and destroying infected cells. The thymus is unique in that it is largest in childhood, and after puberty begins to shrink and become replaced by fat. As the thymus shrinks, we produce less and less new T-cells, therefore reducing T-cell diversity over time. By the age of 75, the thymus is reduced almost completely to fatty tissue. This is a major contributing factor in the increasing susceptibility of the elderly to infection and disease.


Fahy’s theory was that thymus regeneration could improve immune system protection. Therefore, he launched the Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial at Stanford Medical Center in Palo Alto, California. The trial - which recruited nine white men between 51 and 64 - was designed to investigate the possibility of using recombinant human growth hormone (rhGH) to regenerate the thymus and prevent or reverse signs of “immunosenescence” (immune system aging). Because growth hormone is known to promote diabetes, the trial added two widely used anti-diabetes drugs to the treatment course: dehydroepiandrosterone (DHEA) and metformin. This cocktail was unique in the fact that both DHEA and metformin have also been proposed as candidates for slowing aging.


Following a year of treatment using this drug cocktail, the results were positive: participants showed both robust rejuvenation of immune cell populations, and regeneration of thymus tissue. Even more surprising, however, was the resulting “epigenetic age regression”. That is to say, the reversal of biological age.


At the end of the trial, as a sort of afterthought, Fahy approached Dr Steve Horvath, the researcher responsible for breakthroughs in our understanding of the epigenetic clock (read more here). Fahy provided Horvath with before and after samples of the trial participants' blood. Horvath used four different epigenetic clocks (each measuring somewhat different features of aging) to assess each participant's biological age. After one year of treatment, epigenetic (or biological) age was reduced on average by 2.5 years. A follow up done six months after the end of the trail showed that this reduction in biological age continued with some regression after treatment ended, with an average improvement of 1.5 years. In addition, when Horvath used the GrimAge epigenetic clock, which is specifically able to predict human life expectancy, there was no regression after treatment, with a gain of approximately 2.1 life-years according to before and after epigenetic clock markers. Furthermore, comparing the rates of age reversal between months 0-9 and months 9-12 of the trial, the rate of aging reversal appeared to accelerate with increasing time on treatment. This suggests that the longer the drug treatment course, the greater the age reversal.


It is important to highlight that the study used a very small cohort and did not use the scientific gold standard of a double-blind randomized control trial. However, Fahy is planning a larger study, which will diversify participant age, gender, and ethnicity. In addition, it must be pointed out that growth hormone can have pro-aging effects, and the comprehensive consequences of growth hormone exposure may not fully be known. Overall, the study is historic for showing that reversing age is indeed possible, and we impatiently await the follow-up research.


To see Dr Fahy speak on the issue of thymus regeneration and age reversal click here.


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