Reversing the Biological Clock

While the current increasingly aging population and enhanced human lifespan are signs of great advancement in medical technology, population aging also contributes to a variety of socioeconomic, environmental, and healthcare-related difficulties, significantly straining the global economy and healthcare system. The medical community began investigating potential biomedical strategies of reversing the aging process several years ago in the hopes of diminishing cognitive decline, weakening of the immune system, and other negative effects of biological aging. In doing so, researchers have made significant discoveries in the field, one of which now provides a definitive basis of measurement for determining biological age – the epigenetic clock.

Developed by Dr. Steve Horvath, professor of Human Genetics and Biostatistics at UCLA, the epigenetic clock utilizes the body’s epigenome and specifically, changes in DNA methylation state to determine a person’s biological age, which may often exceed or fall behind their chronological age. Dr. Horvath’s discovery has helped to elucidate novel aspects of the aging process and deepen our current understanding, promoting further research efforts aimed at uncovering the complexities of reversing systemic aging. Thus far, attempts at the reversal of biological aging have not been confirmed by epigenetic age changes although the latest trial results from California implicate the potential to effectively reverse the aging process for the first time.

In a small-scale trial, researchers found that a cocktail of medications was able to rejuvenate the human body’s epigenetic clock and regenerate the immune system, according to findings published in Aging Cell.

Reversal of Epigenetic Aging and Immunosenescent Trends

Led by immunologist Dr. George Fahy based in Los Angeles, a small clinical trial aimed to test whether the use of growth hormone could safely restore tissue in the human thymus gland – a vital organ for immune function. Based on prior evidence from animal studies that growth hormone supplementation can stimulate thymus regeneration, researchers conducted the Thymus Regeneration, Immunorestoration, and Insulin Mitigation (TRIIM) study, which included 9 healthy white male volunteers between the ages of 51 and 65.

For a total of one year, the participants consumed growth hormones alongside two common anti-diabetic drugs – dehydroepiandrosterone (DHEA) and metformin – to prevent diabetes development. Researchers gathered blood samples and magnetic resonance imaging (MRI) of the thymus gland at baseline and after the trial period; tests revealed a rejuvenated blood-cell count in all participants and regenerated thymus tissue in 7 patients, indicating immune system revitalization.

Researchers say checking the effect of the medication cocktail on epigenetic clocks was an afterthought; Dr. Fahy only consulted Dr. Horvath after the trial had concluded. In his analysis, Dr. Horvath utilized four different epigenetic clocks to assess each participant’s biological age, finding a substantial decrease for each patient and trial. On average, participants shed 2.5 years of their biological age as per Dr. Horvath’s measurement of epigenetic changes, indicating the promising potential of the medication cocktail to not only rejuvenate the immune system, but to also increase longevity and decrease biological age. Moreover, these results persisted at six-month follow-up in those who provided blood samples, implicating the drugs may have long-term effects.

Researchers were surprised by the study’s findings as they did not expect to discover the reversal of the epigenetic clock, however, the results are still preliminary. Implications of the revived blood cell count are vast for future treatment development of infectious disease and cancer, as well as population aging in general, while regeneration of the thymus can prove vital in the treatment of immunosuppressed patients. Although, due to the small-scale nature of the trial and lack of control subjects, additional research is necessary to support Dr. Fahy’s findings and further elucidate the potential of this pharmaceutical cocktail to reverse the aging process.  Dr. Fahy and his team plan to conduct a larger study – including different age groups, ethnicities, and women – to further investigate the effect of growth hormone and anti-diabetic medications on human biological age.