Alcohol Abuse Makes ‘Epigenetic Clock’ Run Faster

Study Finds Heavy Alcohol Use Accelerates Cellular Aging

By Brandon Levy

Tuesday, October 29, 2019

In an era when 80-year-olds are running marathons while 30-year-olds suffer from obesity-induced heart attacks, inferring the condition of people’s bodies from their birth years is a bit outdated (pun intended). As a result, scientists and clinicians are increasingly examining biological signposts to gauge how well a person’s tissues are functioning. By looking at chemical markers on DNA, IRP researchers recently found that heavy alcohol use accelerates aging at the cellular level.¹

Throughout the genome, there are many sites that can have chemical tags attached to them through a process called DNA methylation. What’s more, past research has shown that methylation levels at some of these sites is linked to a person’s ‘chronological age’ — the amount of elapsed time since his or her birth. However, chronological age is not always a good indicator of a person’s risk for age-related diseases like cancer or cardiovascular disease.

To address this mismatch, researchers developed mathematical algorithms called ‘epigenetic clocks’ that measure the level of DNA methylation at certain genetic locations in order to determine a person’s ‘epigenetic age’ ­— the amount of wear and tear on the tissues in his or her body. Past studies have established that people with a higher epigenetic age than their chronological age, referred to as ‘epigenetic age acceleration,’ are at greater risk of dying² and are more likely to develop certain age-related diseases.³

“In a perfect world, your epigenetic age would be the same as your chronological age,” says IRP Lasker Clinical Research Scholar Falk Lohoff, M.D., the new study’s senior author. “The idea of these epigenetic clocks is that, compared to chronological age, they might be a better measure of how old your body really is.”

As a psychiatrist specializing in addiction, Dr. Lohoff noticed what many of his predecessors had: that patients with substance abuse disorders looked older than they really were. To investigate this observation, he set out to examine whether heavy alcohol consumption affects epigenetic age.

Dr. Lohoff’s team used an epigenetic clock to determine the epigenetic age of 331 people with alcohol use disorder (AUD) and 201 healthy individuals. After controlling for various factors including gender, chronological age, and weight, the algorithm determined that patients with AUD had an average epigenetic age nearly 1.5 years ‘older’ than the healthy group. What’s more, among the individuals with AUD, those who reported drinking large amounts of alcohol more often over the previous 90 days showed more epigenetic age acceleration, as did those with higher levels of certain liver enzymes that are elevated by heavy alcohol consumption.

“It’s really a continuum,” Dr. Lohoff says. “The more severe your alcohol use problem is and the more severely your body is affected, as reflected by changes in your liver enzymes, the more severe your age acceleration is.”

In an effort to understand potential biological mechanisms that could connect AUD and accelerated epigenetic aging, the researchers conducted a genome-wide association study (GWAS) to search for genes that influenced epigenetic aging in the study’s participants. Out of several genes identified by the GWAS, the one most strongly linked to epigenetic age acceleration was the APOL2 gene, which is involved in cell repair and apoptosis, a process by which sick cells destroy themselves. Specifically, participants with AUD who had the less common version of the gene were epigenetically older than their counterparts who had the more common variant. An additional analysis using publicly available data found that, in people with the less common APOL2 variant, the gene was more active in a memory-related brain structure called the hippocampus.

While the new findings hint at how heavy alcohol use might prematurely age the body, the research is still in its early stages. Future studies will need to examine possible biological processes behind the phenomenon in further detail, as well as scour the genomes of many more individuals for additional genes that may be involved.

“Ultimately, the repair mechanisms in your cells fail because your tissue has aged and it can’t repair itself anymore,” Dr. Lohoff says. “I think it will be very important to understand the mechanisms behind why this aging occurs, why this aged tissue is less able to repair itself, and how this makes people more susceptible to cancer and other age-related diseases.”

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References:

[1] Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2. Luo A, Jung J, Longley M, Rosoff DB, Charlet K, Muench C, Lee J, Hodgkinson CA, Goldman D, Horvath S, Kaminsky ZA, Lohoff FW. Neuropsychopharmacology. 2019 Aug 29. doi: 10.1038/s41386-019-0500-y. [Epub ahead of print]

[2] DNA methylation-based measures of biological age: meta-analysis predicting time to death. Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai P, Roetker NS, Just AC, Demerath EW, Guan W, Bressler J, Fornage M, Studenski S1, Vandiver AR, Moore AZ, Tanaka T, Kiel DP, Liang L, Vokonas P, Schwartz J, Lunetta KL, Murabito JM, Bandinelli S, Hernandez DG, Melzer D, Nalls M, Pilling LC, Price TR, Singleton AB, Gieger C,, Holle R, Kretschmer A, Kronenberg F, Kunze S, Linseisen J, Meisinger C, Rathmann W, Waldenberger M, Visscher PM, Shah S, Wray NR, McRae AF, Franco OH, Hofman A, Uitterlinden AG, Absher D, Assimes T, Levine ME, Lu AT, Tsao PS, Hou L, Manson JE, Carty CL, LaCroix AZ, Reiner AP, Spector T, Feinberg AP, Levy D, Baccarelli A, van Meurs J, Bell JT, Peters A, Deary IJ, Pankow JS, Ferrucci L, Horvath S. Aging. 2016 Sep 28;8(9):1844-1865. doi: 10.18632/aging.101020.

[3] Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease. Huang RC, Lillycrop KA, Beilin LJ, Godfrey KM, Anderson D, Mori TA, Rauschert S, Craig JM, Oddy WH, Ayonrinde OT, Pennell CE, Holbrook JD, Melton PE. J Clin Endocrinol Metab. 2019 Jul 1;104(7):3012-3024. doi: 10.1210/jc.2018-02076.

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