This is the second post in a series about slowing the aging process and even reversing biological aging. The first post was 7 Steps to Slow and Even Reverse Aging.
A Huge Threat to Health & Longevity, Even in Healthy People, as We Get Older
One of the biggest threats to the health and longevity of otherwise healthy people as they get older is infections like pneumonia.
This is because as people age their immune function declines due in part to the shrinking or "involution" of the thymus gland throughout life. So a person could be doing everything right for their general health yet be taken out by something like pneumonia. This is quite common.
Consequently, regenerating the thymus gland and immune function would be an important focus of any efforts to slow and reverse aging. Fortunately, there does seem to be a solution that accomplishes just that.
A Potential Solution to Age-Related Immune System Decline
Since it has been observed that growth hormone can regenerate the thymus gland in rodents, Gregory Fahy, PhD and other scientists wanted to find out if the thymus gland could be regenerated in humans, using growth hormone.
The scientists conducted a study that included injections of growth hormone and the ingestion of four other substances: the drug Metformin, the steroid prohormone DHEA, the fat-soluble vitamin D, and the mineral zinc.
The Metformin and DHEA were chosen to mitigate growth hormone's insulin-raising effect. And vitamin D and zinc were chosen because of their important roles in the immune system.
Thymus Regeneration, Immunorestoration, and Insulin Mitigation
In the Thymus Regeneration, Immunorestoration, and Insulin Mitigation (TRIIM) trial, nine men between the ages of 51 and 65 participated in a one-year study during which they received growth hormone injections, Metformin, DHEA, vitamin D, and zinc. At the end of the trial, the men showed improvements in numerous markers of immune function that were interpreted as signs of thymic regeneration.
There were also some other unexpected benefits. Prostate specific antigen (PSA), a marker of prostate inflammation or cancer, came down. C-reactive protein (CRP), a marker of inflammation, was reduced. Kidney function improved. Hair color darkened. And epigenetic age (as measured by DNA methylation clocks) was reduced by about one and a half years by the end of the one-year trial, for a total reduction in biological age of about two and a half years.
The promising results of Fahy's first trial have spawned an expanded trial (TRIIM-X) with more participants, including women, and a broader age range from 40 to 80. And so far, the preliminary results look promising.
An interesting feature of the results of the first trial was that the improvements between months 9 and 12 were far greater than those between months 0 and 9, raising the question of whether extending the trial beyond one year might produce exponentially better results.
And I have heard anecdotally that study participants who continued applying the trial interventions after the trial was over achieved reductions in epigenetic age (DNA methylation age) of up to 10 years in a period of about 2 years.
So could something like this approach be continued for longer periods? Some people question the use of growth hormone as a longevity strategy.
Is Growth Hormone Safe?
Some researchers on human aging, such as David Sinclair, PhD, focus exclusively on "longevity pathways" (promoted by things like calorie restriction) and are wary of "growth pathways" (promoted by things like growth hormone). Sinclair's dominant focus is "adversity mimetics" like calorie restriction, protein restriction, and phytonutrients like resveratrol.
Researchers who share Sinclair's focus on longevity pathways express concern that increasing growth hormone levels could be harmful to the goal of longevity or could increase the risk of cancer.
However, even high doses of growth hormone in adult animals have not been shown to reduce lifespan or to increase cancer in animals. Research on humans is sparse on this topic, but it is probably prudent to avoid taking growth hormone while treating cancer.
Aside from that, concerns about growth-promoting agents like growth hormone and protein appear to be largely theoretical and phobic of "growth pathways" like mTOR, which actually becomes increasingly difficult to activate as we get older.
So the "risk" of overactivating growth pathways actually diminishes as we get older, while our supply of growth-activating agents like growth hormone and DHEA also decline. So it does not make any sense in the context of advancing age to restrict growth hormone (or protein, or calories, etc).
Maintaining human growth hormone (or DHEA) within the range of youthful physiological levels has not been shown to cause problems in humans either. However, when the source of growth hormone is injections, sometimes symptoms of carpal tunnel pain or other joint-related can pain occur.
Some study participants experienced finger stiffness, and one experienced temporary carpal tunnel symptoms that went away with a temporary cessation of growth hormone injections. But to my knowledge such symptoms do not occur with more natural means of increasing growth hormone, such as the use of certain peptides to stimulate the body's own release of its own growth hormone.
Is Metformin a Good Idea?
Some trial participants also experienced side effects from Metformin, such as vomiting. This is quite common with Metformin and is a frequently cited reason that people stop using it after a while.
Metformin became popular among longevity enthusiants (e.g. David Sinclair, PhD) because in early research it seemed to show longevity-promoting benefits. But more recent research on Metformin has called into question previous conclusions about the purported longevity-promoting benefits of Metformin.
An Alternative to Metformin
I believe that Metformin is a poor choice for attempting to counter the potential insulin-raising effect of growth hormone because it supposedly does so by increasing mitochondrial biogenesis by impairing mitochondrial function. But impaired mitochondrial function is the main cause of poor blood sugar metabolism in the first place. So using Metformin to improve blood sugar regulation seems a bit like trying to fight fire with fire.
As an alternative to Metformin, the natural compound berberine has been compared to Metformin because it lowers blood sugar. Berberine also has mild antimicrobial effects that lower endotoxin production in the gut.
I recommend berberine along with other natural compounds that lower blood sugar to my clients that have elevated blood sugar, insulin resistance, and diabetes.
Should DHEA Be Taken Alone?
When DHEA is given to men, often too much of it converts to estrogen, especially when systemic inflammation is present, as is the case among average American males in the age range that particpated in the TRIIM trial. The conversion to estrogen can be reduced by using aromatase inhibitors. But the TRIIM trial did not use aromatase inhibitors or measure estrogen, which I believe are major oversights in the trial design.
The Nutritional Components of the TRIIM Trial
The inclusion of vitamin D in the trial made sense, but it did not make sense to not also include vitamins K2 and A, which are essential for healthy vitamin D function. Supplementing with vitamin D but not K2 could contribute to calcium buildup in soft tissues such as the endothelial lining of arteries.
This is because K2 is necessary for the proper function of proteins that depend on both vitamins D and K2 to direct their function toward placing calcium in hard tissues like bone instead of soft tissues like artery walls.
It also made sense to include zinc in the trial, but it can be problematic to supplement with zinc without monitoring copper status and potentially also supplementing with copper. This is because zinc competes with copper for absorption and can potentially increase the excretion of copper.
Research has demonstrated that a copper deficiency can be created within just two weeks of supplementing with zinc at normal doses. This does not mean that zinc supplementation will always create copper deficiency, but it can happen.
Copper has many key roles, including as a cofactor in the mitochondrial energy production enzyme cytochrome c oxidase, the antioxidant enzyme superoxide dismutase, and several proteins involved in iron metabolism. A copper deficiency can create major problems, so it's important to avoid inadvertently creating (or worsening) a copper deficiency with zinc supplementation.
Hope for Your Immune System in Old Age
Overall, the TRIIM trial was a major success and provides evidence that the thymus gland and immune function can be regenerated even as we get older. However, the methods used could be improved to make them safer and more intelligent hormonally and nutritionally.
The methods could also be modified to make this process more accessible, appealing, and affordable to people who would not want to use prescription-only drugs or hormones, or who cannot afford to do so. I have modified the methods of the TRIIM trial for myself and am following my own version of the TRIIM trial methodology.
This is something I can show to clients when they are ready. To learn more about how I work with clients, download the Bio-Individual Blueprint Roadmap, and watch the walkthrough video.
In the next post, I will cover the "hallmarks of aging" that researchers have identified as characterizing the aging process. We must understand these hallmarks in order to counteract them.