Maybe you missed it, but last week was a big week in the news of technology and the science of aging. A small study conducted by a team of researchers that included Dr. Steve Horvath reported that individuals who were fed a human growth hormone cocktail for over a year demonstrated a reversal in biological aging—in other words, they became younger.[1] “What,” you say? That’s right, the ten individuals who took the drug cocktail showed a reversal in their biological age by an average of 2.5 years, compared to those with no treatment at all. As the researchers reported: “This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.”
This research focuses on the notion of aging as a disease—an idea that continues to grow in its understanding and acceptance among academics, researchers, and clinicians. The study sought to confirm that systemic aging can be reversed by determinations of epigenetic age, which provides a simple but compelling indication of biological as opposed to chronological age. The study further sought to specifically address immunosenescence stemming from thymic involution (a precipitous decline in the thymus gland and the immune system). Thymic involution leads to the depletion of critical immune cell populations, resulting in a collapse of the T‐cell receptor (TCR) repertoire in humans after the age of ~63, and is linked to age‐related increases in cancer, infectious disease, autoimmune conditions, generalized inflammation, atherosclerosis, and all‐cause mortality. In contrast, maintaining a well-functioning immune system is well observed in centenarians.
While the study was small in scale, with a total of ten male individuals participating, it was exciting to see the confidence in the results and the use of epigenetic clocks in measuring the change in biological age. The study was somewhat controversial in that the individuals were prescribed what might be best described as a human growth hormone cocktail “lite”—think Barry Bonds Lite. There was a noted apprehension that the cocktail could spur concerns commonly associated with human growth hormones, but in this case the benefits seem to far outweigh the risks or side effects.
As a base indicator of the benefits of the cocktail, researchers documented the response to the thymus gland—a gland critical in our immune system functioning. The amazing thing about the thymus is that, unlike most organs, it is at its largest in children. Once you reach puberty, the thymus starts to slowly shrink and become replaced by fat. By age 75, the thymus is little more than fatty tissue.
In the study, researchers observed qualitative improvements in thymic MRI density and are illustrated in the figure below:
The picture is an example of a treatment‐induced change in thymic MRI appearance. Darkening corresponds to the replacement of fat with nonadipose tissue. White lines denote the thymic boundary.
This study is important because researching aging as a disease is a major challenge since it is not recognized by regulatory authorities as a disease, or as a valid target of clinical trials. As a result, research (dollars) has focused on tests for drugs that address specific diseases rather than the mechanisms of aging and other age-related conditions. The issue is that polymorbidity (the presence of multiple conditions at once) is generally what kills you as you age. This concept is embedded in the idea of measuring all-cause mortality. As it has been often said, it is not one thing that kills you as you age, it is everything. Researching drugs that target aging will require new covariate measures of outcomes with older people. In the future, a “polypill” that targets the different biological systems involved in aging may provide individuals protection from that which kills us.
Today we have a trickle. Tomorrow we will have a stream. And
soon we will have a river. And then will
we cure the disease of aging. Stay tuned!
[1] https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028