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The human immune system loses function with age in a process known as immunosenescence. Previous research has reported on the ability of a number of drugs to impact the aging process; however, these studies have not measured the ability to reverse epigenetic aging. Research from epigenetics expert Steve Horvath is the first to demonstrate the reversal of epigenetic aging and immunosenescence of the thymus with drug therapy.

The thymus is an immune organ necessary for the development of T cell populations. After the age of approximately 63, a process called thymic involution severely impairs T cell function and is linked to increases in cancer, infection, autoimmune conditions, chronic inflammation, and heart disease.

Nine participants between the ages of 51 and 65 years were given a drug protocol that included recombinant human growth hormone to reverse signs of immunosenescence. Because growth hormone can increase insulin production to a harmful degree, the authors used metformin, a common diabetes drug, and dehydroepiandrosterone, a steroid precursor, to control symptoms of diabetes. The investigators collected white blood cells to measure immune characteristics and epigenetic age.

Following one year of treatment, the authors reported an average decrease in epigenetic age of 1.5 years over baseline, meaning they reversed epigenetic age by 2.5 years over the course of the study. Participants demonstrated an increase in t cell production and an increase in the leukocyte/monocyte ratio, a measure of immune cell populations that is associated with less inflammation and lower rates of several cancers. Monocytes use a lot of nicotinamide adenine dinucleotide (NAD+), which is an important energy source for cells. The authors suggested this decrease in monocytes and subsequent increase in NAD+ may be responsible for the reversal of epigenetic aging.

The main purpose of this pilot trial was to determine the safety and efficacy of the study treatment. Larger studies with a control group are needed to expand on these results.

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