Turning Back the Epigenetic Aging Clock

Aging is a major factor associated with chronic disease, which accounts for nearly two thirds of all deaths and contributes to approximately 75% of annual health care costs in the United States1. As scientists and doctors search for novel therapies and interventions to deal with aging and related diseases, the epigenetic clock has emerged as an important tool able to predict biological, as opposed to chronological, age in mammals2,3. Now, a new study provides the first evidence that reversal of biological age in humans may be possible4.

A 3-Part Treatment Cocktail

As a primary objective of their study, Fahy et al. administered a year-long, 3-part treatment cocktail consisting of recombinant human growth hormone, dehydroepiandrosterone (DHEA), and metformin to restore age-related decline of thymus function in male research subjects ranging from 51-65 years of age5. Using a variety of quantitative and qualitative techniques (MRI, blood cellular composition, cytokine signaling, and inflammation), the authors reported strong signs for reversal of the thymic damage and declining immune function often associated with age.

Turning Back the Clock

The authors next measured the biological age of each study participant using the epigenetic clock – identifying it as a simple yet compelling way to assess systemic aging. In agreement with the immunological and thymic measurements, Fahy et al. found an average reduction of 2.5 years of biological age in the research subjects. Furthermore, the age reversal seemed to accelerate the longer the recipients received treatment. Importantly, the age-related therapeutic benefits persisted up to 6 months after treatment concluded.

Whereas earlier studies showed that the epigenetic clock could be slowed down through various lifestyle or environmental modifications6, the study by Fahy et al. represents the first evidence that biological age is reversible. Commenting on their work, the authors noted that the epigenetic clock “…is the most accurate measure of biological age and age‐related disease risk available today. This justifies the use of epigenetic clocks to estimate the effectiveness of putative aging interventions on a practical timescale.”

Zymo Research now offers DNAge Services, a Next-Gen Sequencing based platform to analyze the biological age of human and mouse DNA samples. Zymo Research’s technology expands upon the original epigenetic clock by utilizing bisulfite sequencing and a unique capture strategy to target a panel of DNA methylation biomarkers that are highly informative of aging. The DNAge Epigenetic Clock Service can be applied to not only anti-ageing intervention studies but also investigation of age-related diseases.

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References:
1. Raghupathi, W. , and Raghupathi, V. An empirical study of chronic diseases in the United States: A visual analytics approach to public health. Int J Environ Pres Public Health. 15(3):431 (2018).
2. Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, R115 (2013).
3. Field, A. E. et al. DNA methylation clocks in aging: categories, causes, and consequences. Mol. Cell 71, 882–895 (2018).
4. Abbott, A. First hint that body’s ‘biological age’ can be reversed. Nature 573, 173 (2019).
5. Fahy, G.M. et al. Reversal of epigenetic aging and immunosenescent trends in humans, Aging Cell (2019). DOI: 10.1111/acel.13028
6. Quach, A. et al. Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging 9, 419–446 (2017).