Evaluating the Reversal of Aging in a Preliminary TRIIM Study

Unraveling the Riddle of Aging Reversal:  Realities and Cautions of a Preliminary TRIIM Study

Key Takeaway

A recent study suggests that it is possible to reverse aging to some extent. Nine healthy men who were given a cocktail of human growth hormone (hGH), metformin, DHEA, vitamin D3, and zinc for one year showed a reduction of about 2.5 years in their biological ages.

Article Summary
 

• A recent study published in Aging Cell suggests that it may be possible to reverse aging.
• Nine healthy men participated in the study and were given a cocktail of hGH, metformin, DHEA, vitamin D3, and zinc for one year.
• The study aimed to investigate whether using hGH in men in their 50s and early 60s can prevent or reverse signs of immune system deterioration.
• The lead investigator of the study, Greg Fahy, wanted to see if he could regenerate the thymus and restore immune system function using hGH.
• The study showed that the participants' epigenetic age decreased by about 2.5 years, while their chronological age increased.
• The study lacked a control group and had a small sample size, consisting of only 9 healthy men.
• The study raised questions about which component of the cocktail was responsible for the improvement and whether it was the intervention itself or other factors that accounted for the results.
• The study also discussed the accuracy of epigenetic clocks, the tool used to measure biological age.
• The study showed promising results in terms of thymic regeneration and improvements in age-related immunological parameters.
• Further research is needed to validate and understand the findings of this study.

The world population aged 60 or over doubled in the last 30 years
 

This number is expected to double again by 2050, a new study published in Aging Cell raises intriguing possibilities. This headline highlights the significance of the study's findings in the context of a rapidly aging global population.

A recent study published in Aging Cell suggests that it may be possible to reverse aging to some extent. The study involved nine healthy men who were given a cocktail of human growth hormone (hGH), metformin, DHEA, vitamin D3, and zinc for one year. Led by Greg Fahy, the study aimed to investigate whether using hGH in men in their 50s and early 60s can prevent or reverse signs of immune system deterioration. 

The results showed that the participants' epigenetic age decreased by about 2.5 years, while their chronological age increased. However, the study lacked a control group and had a small sample size. As a result, questions were raised about which component of the cocktail was responsible for the improvement and whether it was the intervention itself or other factors that accounted for the results. The study also discussed the accuracy of epigenetic clocks, the tool used to measure biological age. Despite these limitations, the study showed promising results in terms of thymic regeneration and improvements in age-related immunological parameters. 

People are now asking whether they should consider taking human growth hormone (hGH), metformin, or DHEA. 

To help with that question, let us look closer at measuring epigentic aging. In the realm of epigenetic clocks, there exist various types that make different predictions, such as the time to cardiovascular disease or mortality. Some clocks even combine additional biomarkers with DNAm (DNA methylation) to create a composite biomarker. Horvath and colleagues, in their publication introducing one of these clocks called DNAm GrimAge, state that while technically it serves as a mortality risk estimator, metaphorically it estimates biological age.

Remarkably, in the recent study, the reversal of epigenetic clocks was observed for the first time in a human trial, as stated by Horvath himself. This discovery raises the question: Can humans truly reverse their biological age, and does the study provide evidence for such a phenomenon? According to the article titled "Humans Can Reverse Their Biological Age, Shows a 'Curious Case' Study," the answer to both parts of the question is a resounding yes.

Reverse Aging Yes, But Hold those Horses

One important aspect to consider in the study is that the epigenetic clocks used to estimate biological age were based on DNA methylation patterns specifically in peripheral blood mononuclear cells (PBMCs), which include lymphocytes and monocytes.
 
So, the clocks solely focused on these cells to determine epigenetic age, without taking into account other cells and tissues, such as liver, muscle, or adipose tissue, in the body. Steve Horvath, in communication via email, explained that the concordance of age acceleration between PBMCs and other cells and tissues is only weak to moderate, with an average correlation of around 0.3 in cross-tissue comparisons.

This raises an important question: While the lymphocytes may exhibit a more youthful phenotype after the one-year intervention, it does not necessarily mean that the rest of the body followed suit. This is crucial because reversing "global" aging would likely require the rejuvenation of multiple cells and tissues, not just one component. If only certain cells or tissues are impacted, it may not lead to a comprehensive reversal of aging.

Furthermore, it's essential to note that epigenetic alterations form just one of the nine known hallmarks of aging. While the study's treatment may have influenced this aspect and potentially increased longevity, we must not overlook the fact that aging is a multifaceted process with mechanisms beyond DNA methylation. For instance, rapamycin is widely considered an effective compound to target aging directly, yet none of the clocks used in this study detected its anti-aging effect. This suggests that certain methods of extending lifespan may not be captured by DNAm clocks focused on estimating changes in biological age.

Trying to Regenerate The Thymus

It is also worth mentioning that the study primarily aimed to regenerate the thymus, which was assessed through MRI measurements of the thymic fat-free fraction (TFFF) and bone marrow fat-free fraction (BMFFF). The reported increase in TFFF and a lesser increase in BMFFF indicated an apparent reversal of thymic involution, as adipose tissue that had replaced functional thymus.

Keeping a cautious approach to the study's findings is understandable and reasonable. It is important to critically evaluate and consider the limitations of any research before making significant decisions, especially when it comes to patient care and an individuals health.

Indeed, this particular study has several limitations, including its small sample size, short duration, and lack of a control group. These factors make it challenging to establish a direct cause-and-effect relationship between the intervention and the observed reversal of aging, as represented by epigenetic clocks. Additionally, the study focused solely on estimating age based on DNA methylation patterns in one specific blood cell type, which further restricts the generalizability of the findings to other tissues or cell types.

Relying on more robust and comprehensive evidence before implementing any medical intervention is crucial in ensuring patient safety and well-being. As time progresses and further research is conducted, the scientific community will gain a better understanding of the potential benefits and risks associated with interventions such as hGH, metformin, and DHEA for anti-aging purposes.

Until then, maintaining a cautious approach and prioritizing evidence-based medicine remains prudent. appeared to be partially replaced with more functional tissue.

Further Study is Needed , Going further than TRIIM

While the study measured the number of different immune cell populations, such as monocytes and lymphocytes, it did not evaluate their functionality, which is a crucial factor to consider. The functionality of immune cells may hold greater importance than their numbers alone.

Therefore, although there are indications of epigenetic clock reversal based on DNAm patterns in PBMCs, it is challenging to ascertain if such a reversal is solely due to thymic regeneration, particularly because the study lacked a control group.

Lastly, it is important to remember that DNA methylation is just one part of the equation, and it does not provide insights into transcription (the process of RNA production from DNA) and translation (protein synthesis from RNA). Many additional steps are required to translate DNA changes into a phenotype, whether it be positive or negative, and these cannot be directly measured. Furthermore, the predicted phenotype resulting from DNA changes is still unclear in many cases.

Given these considerations, questions arise regarding the probability that the intervention itself was responsible for the observed improvement in the aging clocks. In other words, what are the odds that individuals should consider taking the cocktail of hGH, metformin, and DHEA? Conversely, what are the chances that other factors unrelated to the intervention contributed to the observed improvement?

Unfortunately, due to the lack of a control group, it is virtually impossible to answer these questions. Without a control group, it is challenging to minimize the effects of variables beyond the intervention itself. We cannot discount the possibility that other behaviors or factors exhibited by the participants may have contributed to some or all of the observed improvements. Additionally, understanding the participants' baseline epigenetic age at the start of the study could provide valuable insights into their health status.

Current Conclusion

A cautious approach to the study's findings is understandable and reasonable. It is important to critically evaluate and consider the limitations of any research before making significant decisions, especially when it comes to patient care.

Indeed, this particular study has several limitations, including its small sample size, short duration, and lack of a control group. These factors make it challenging to establish a direct cause-and-effect relationship between the intervention and the observed reversal of aging, as represented by epigenetic clocks. Additionally, the study focused solely on estimating age based on DNA methylation patterns in one specific blood cell type, which further restricts the generalizability of the findings to other tissues or cell types.

Relying on more robust and comprehensive evidence before implementing any medical intervention is crucial in ensuring patient safety and well-being. As time progresses and further research is conducted, the scientific community will gain a better understanding of the potential benefits and risks associated with interventions such as hGH, metformin, and DHEA for anti-aging purposes. Until then, maintaining a cautious approach and prioritizing evidence-based medicine remains prudent.