DNA Methylation & The Epigenetic Clock: The Science Of How Heavy Smoking & Drinking Speeds Up Aging

Cigarette smoking and heavy alcohol use cause epigenetic changes to DNA that reflect accelerated biological aging in distinct, measurable ways, according to research presented at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore. Using data from the publicly available Gene Expression Omnibus, Robert A. Philibert, MD, PhD and colleagues at the University of Iowa and other institutions analyzed patterns of DNA methylation (an epigenetic mechanism used by cells to control gene expression. A number of mechanisms exist to control gene expression in eukaryotes, but DNA methylation is a commonly used epigenetic signaling tool that can fix genes in the “off” position). Prior research had shown that methylation patterns change in predictable ways as people age, as well as in response to environmental exposures, such as cigarette smoke and alcohol. In these earlier studies, Dr. Philibert’s laboratory identified two specific locations in the genome, base pairs cg05575921 on the AHRR gene and cg23193759 on chromosome 10, at which methylation levels were highly associated with smoking and alcohol consumption, respectively.

In fact, they showed, DNA methylation levels at these two locations was a better measure of substance use than people’s self-reported estimates. Thus, in this follow-up study, Meeshanthini Dogan, MS, and Dr. Philibert used methylation levels as a proxy for tobacco and alcohol consumption. They estimated each person’s biological age using a previously validated epigenetic “clock” based on methylation levels at 71 locations in the genome, as measured by the widely used Infinium HumanMethylation450 BeadChip. Then, they calculated the difference between biological age and chronological age, and assessed the relationship between tobacco and alcohol use and premature aging.

They found that all levels of exposure to smoke were associated with significantly premature aging.
Interestingly, moderate alcohol use — about one to two drinks per day — was correlated with the healthiest aging,
while very low and high consumption were linked to accelerated aging.

“These new tools allow us to monitor smoking and alcohol use in an objective way, and to understand their effects quantitatively,” Ms. Dogan said. “Furthermore, our methods could be used to analyze any set of 450 BeadChip data, which means that existing data can be used to identify new patterns and that all such results can be easily compared.” Dr. Philibert adds: “Being able to objectively identify future smokers and heavy alcohol users when they are young, before major health issues arise, can help providers and public health practitioners prevent future problems, improve quality of life, and reduce later medical costs.”

The researchers’ next step is to unravel the details of how methylation patterns change in response to lifestyle changes during the life course, so that their assessments can be more informative. “For example, we want to study how the intensity of current tobacco and alcohol use and cumulative levels of use throughout a lifetime affect methylation, including what happens when a person quits smoking or drinking,” Ms. Dogan said. “By clarifying at what point the epigenetic changes become tougher to stop or reverse, we can inform decisions about how best to use the limited public health resources we have.”

One of the most important markers of your biological age is the length of your telomeres (strands of DNA which are found on the ends of our chromosomes and prevent chromosomal deterioration — akin to the plastic tips on the ends of our shoelaces). Telomeres shorten naturally, albeit at a very slow rate. But various factors can accelerate telomere-shortening, thereby speed up the aging process as well — and nothing eats away at your telomeres more than free radicals (i.e. free radicals are produced in the body upon exposure to stress, cigarette smoke, alcohol, toxins found in personal care products, pesticides in foods, radiation from the sun, viruses, germs or fungi etc. Antioxidants are able to shut down free radicals before they cause damage).

One fascinating telomere research study, involving a group of breast cancer patients, tracked these women as they engaged in a thorough mindfulness meditation regimen, and when all was said and done it was these women whose telomeres had preserved themselves almost perfectly with DNA regeneration, compared to the two control groups of women who did not participate in the meditation. The cancer patients who did not take part in the meditation had telomeres which had deteriorated noticeably. Telomeres shorten considerably as we age, but abnormally shortened telomeres are found in people with severe or chronic illnesses such as diabetes, heart disease, cancer, etc.

The results were published by the American Cancer Society, including the following excerpt: “To our knowledge, the current study is the first report to demonstrate a potential effect of these psychosocial interventions on TL among distressed breast cancer survivors. There was little discernment between MBCR and SET. Both maintained TL over the 3-month intervention period, whereas women in the control condition demonstrated a trend toward decreases in relative TL. Similarly, in our previous report of the larger parent trial, both the MBCR and SET groups maintained the steepness of salivary cortisol slopes compared with those in the control group, whose slopes became flatter, largely due to elevations in evening cortisol levels. [4] Together, these changes suggest an effect of the interventions on potentially important biomarkers of psychosocial stress. Given the increasingly well-documented association between TL and cancer initiation [46] and survival, [47] this finding adds to the literature supporting the potential for stress-reducing interventions to impact important disease-regulating processes and ultimately disease outcome.” You can read the full study at Wiley.com. And for a list of 7 great tips on how to keep your telomeres from getting shorter and aging you faster be sure to visit Prevention.com. (Image courtesy of The Prisma).