How Drinking Alcohol Impacts Aging with Lifang Hou, MD, PhD

“Our study found that accumulative alcohol consumption overall, and of liquor specifically, both influence epigenetic age. On the other hand, binge drinking may only have more short-term effects.” 
- Lifang Hou, MD, PhD 

• Director, Center for Global Oncology, a joint center between the Robert J. Havey, MD Institute for Global Health and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University
• Chief of Cancer Epidemiology and Prevention in the Department of Preventive Medicine 
• Professor of Preventive Medicine in the Division of Cancer Epidemiology and Prevention and Pediatrics 
• Member of Northwestern University Clinical and Translational Sciences Institute  
• Osher Center for Integrative Health

Hou is an epidemiologist with a multidisciplinary background in medicine and basic science. She and her colleagues examined whether cumulative alcohol consumption as well as the presence of recent binge drinking were associated with four measures of age-related epigenetic age acceleration.   

• Once a practicing physician, Hou pivoted to epidemiology and human genetics in order to investigate disease prevention at a large scale. Her research today looks broadly at lifestyle and environmental risk factors for disease as well as biomarkers that indicate future disease risk. 
• Exposure to certain risk factors can lead to biological changes in the body, which accumulate over time and may eventually cause disease. Developing measurements for these biomarkers can help predict disease and quantify the risk of developing them. 
• In a clinical setting, these biomarkers can provide accurate information on a patient's health behaviors and their impact, facilitating discussions on unhealthy behaviors or acting as early warning signs for disease, and prompting lifestyle changes or aggressive preventive measures. 
• Biological age, also known as molecular age, encompasses various biological markers associated with aging, with epigenetic age (DNA methylation age) being one such marker. Scientists have found that certain epigenetic biomarkers can reflect environmental exposure history. 
• Investigators have developed an algorithm using epigenomic sites to determine epigenetic age. Utilizing the CARDIA cohort, a well-established study of young adults followed for over 35 years, researchers used detailed data to construct a measure of cumulative alcohol intake to examine its relationship with the epigenetic aging process. 
• There are four measures of epigenetic aging in this investigation: intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration. 
• Based on data gathered from the CARDIA study, Hou and her team found that accumulative consumption of liquor influences epigenetic age. Additionally, they observed individuals who are younger in age exhibited greater epigenetic age compared to older individuals, suggesting chronological age in the setting of alcohol consumption may affect aging differently.  
• Several studies have identified healthy lifestyle behaviors can result in younger epigenetic age. However, more research is required to determine whether epigenetic age can be deliberately altered.  
• Hou hopes to look at the cumulative exposure of alcohol in a longitudinal setting to further understand the dynamics of epigenetic age as well as exploring whether alcohol cessation can reduce accelerated epigenetic aging caused by alcohol consumption. 

Additional Reading  

• Read Hou’s latest research which found more green spaces are linked to slower biological aging 
• Discover more about the CARDIA study
• Browse Hou’s publications

 Recorded on March 15, 2023.

Target Audience

Academic/Research, Multiple specialties

Learning Objectives

At the conclusion of this activity, participants will be able to:

1. Identify the research interests and initiatives of Feinberg faculty.
2. Discuss new updates in clinical and translational research.

Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure Statement

Lifang Hou, MD, PhD, has nothing to diclose. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. Feinberg School of Medicine's CME Leadership and Staff have nothing to disclose: Clara J. Schroedl, MD, Medical Director of CME, Sheryl Corey, Manager of CME, Allison McCollum, Senior Program Coordinator, Katie Daley, Senior Program Coordinator, and Rhea Alexis Banks, Administrative Assistant 2.

Claim your credit

[00:00:00] Erin Spain, MS: This is Breakthroughs, a podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, host of the show. Alcohol consumption has previously been linked to the development of disease, but how does alcohol consumption, especially long-term consumption, as well as binge drinking, impact us genetically? Dr. Lifang Hou, chief of Cancer Epidemiology and Prevention and the Department of Preventive Medicine joins me to discuss this question as well as the link between genetics, lifestyle, and environment when it comes to preventing disease. She recently led a Northwestern Medicine study examining the relationship between alcohol and epigenetic age acceleration.Welcome to the show. 

[00:00:58] Lifang Hou, MD, PhD, MS: Thank you for having me. 

[00:01:00] Erin Spain, MS: You're an epidemiologist with a multidisciplinary background in medicine and basic science, and a lot of your research is focused on cancer, but your main overarching goal is to understand the link between genetics and environment when it comes to preventing disease. So tell me more about your work. 

[00:01:18] Lifang Hou, MD, PhD, MS: I am a trained molecular epidemiologist, trained in medicine, basic science and population science. So my work focuses on finding risk factors in our life. For example, our lifestyle or the environmental, and what biological changes or changes at the molecular level by these risk factors, may lead to diseases. So this is important to us to not only understand the causes of diseases, but also the biological changes of the diseases. Because before the disease development, this biological changes in our system, for example, in our blood, in our organs, can guide us in disease prevention and can also let us know what are the levels of the risk exposure at the limit. So this work guides the policy makers in policy making and also helps the scientist engineers to develop a diagnostic or screen tools for disease. 

[00:02:19] Erin Spain, MS: Tell me a little more about your background. You were actually a practicing physician for a while, but early on in your career you pivoted from the clinic to researching populations for causes of disease instead. Tell me about this switch and why it was so necessary in your mind to really further what we know about disease prevention. 

[00:02:37] Lifang Hou, MD, PhD, MS: Yes, I was more interested in understanding the patterns of the the patterns of the risk factors that may cause diseases more than just treating individual patients. I believe that understanding the patterns or prevalence of certain risk factors and how they cause diseases will make contributions in the prevention of the disease at larger scale. I think is the main motivation for me pursued further education to get a PhD in epidemiology and the human genetics. 

[00:03:12] Erin Spain, MS: So you look broadly at lifestyle and environmental risk factors as potential indicators of disease, but you also look at biomarkers that indicate past exposure as well as future disease risk. So let's drill into this a little bit further. Tell me about these two categories that you study more specifically. 

[00:03:32] Lifang Hou, MD, PhD, MS: I think these are two sides of the same coin. Exposure to certain risk factors causes some biological changes in human systems or organs, for example, in our blood or specific organs in our brain, liver, or kidney. So if the exposure continues, the biological changes will accumulate over time in response to the continuous exposure. So the biomarker of risk exposure tells us how the exposure may cause a certain change in our system. We call it a biomarker of exposure. However, when the accumulation of certain biological changes reaches a certain point, it will cause some biological or pathological changes that may lead to disease development. So this late stage biological changes may help us to predict certain diseases. So we aim at developing measurements, not just of past exposure but also its accumulative biological impact that may help physicians, scientists to predict certain diseases. This will in turn help us quantify the risk of getting a disease as a result of that accumulation. So our ability as a researcher to study one or the other is mainly currently dictated by the type of data on which we have access. But in the doctor's office, both could be used to test the blood of healthy individuals. In one case, it would give the doctor a more accurate measurement of the patient's health behaviors and their biological impact, which would give them more information to facilitate a discussion of unhealthy behaviors with their patient. In the other early detection biomarker could serve as a early warning of disease, signaling to the patients and the clinicians that it is time for lifestyle change or more aggressive, preventive or interventive measures. 

[00:05:41] Erin Spain, MS: And what we eat, drink, how much we exercise, where we live, how we handle stress -- these are just some of the variables that can interact with our genes and influence disease. And these factors also influence both biological age and what's called epigenetic age. So define these terms for me: biological age versus epigenetic age. How are they calculated? 

[00:06:03] Lifang Hou, MD, PhD, MS: So biological age, we also call it the molecular age, is a sort of catch-all term. It can be referred to a wide range of different biological merits that have been associated with aging process in different ways. So epigenetic age is also referred as DNA methylation age is just one of the merits of biological age.So epigenetic age uses more about 100 epigenomic changes that have been closely associated with our chronological age. Scientists have found that this epigenetic biomarkers can reflect our environmental exposure history and closely relates to our chronological age. And then we have developed an algorithm. Scientists have found that about a hundred, epigenomic sites are closely related to human chronological age and turned that into a algorithm. And we referred as a, epigenetic age. Epigenetic age is designed to be comparable to our chronological age, but the different technology used in the models means that different measures of epigenetic age can tell us different things about what is going on under the hood as we age. 

[00:07:30] Erin Spain, MS: So this specific study that we're talking about today has to do with alcohol. And alcohol consumption has long been understood to compromise health, but its effects on aging are under researched. Tell us about this study that you led with your colleagues looking at alcohol consumption and epigenetic age acceleration in young adults. What did you find? 

[00:07:53] Lifang Hou, MD, PhD, MS: We have been very fortunate to have the opportunity to work with the CARDIA cohort, which is a very well established and famous cohort of young people who were enrolled into this study in their early thirties. And they have been followed up for more than 35 years. During the follow-up, they have been examined for various health outcomes, including their subclinical, environmental, lifestyle, and many other outcomes. So alcohol is one of the lifestyle factors that have been studied over time. So the uniqueness of our study really reflects the strengths of the CARDIA cohort. We have detailed information about the study subjects' alcohol consumption going back decades. Adapting the idea of smoking a pack a year that mirrors cumulative behavior of smoking, we also constructed a measure of accumulative alcohol consumption, and we examined how the overtime alcohol consumption may be related to their epigenetic aging process. 

[00:09:07] Erin Spain, MS: And epigenetic aging you just told us a little bit about. There are actually four measures of epigenetic aging in this investigation. Tell me about these different measures and what they mean. 

[00:09:19] Lifang Hou, MD, PhD, MS: So the fundamental approach to all four is similar. All four makes use of large statistical model that sifts through the hundreds of thousands of methylation or epigenetic sites in human epigenome. And they look for specific sites. Three measures of epigenetic age look for sites that are associated with chronological age. One of these intrinsic epigenetic age is desire to capture cellular aging. This makes it in some sense the purest measure of biological age, independent of environmental factors. The second of this, extrinsic epigenetic age, is designed to capture aging in immune cells specifically and is more sensitive to environmental effects. Finally, there is one also called the PhenoAge. From the name you can tell this measure was designed to capture size related to age related diseases and physical functioning. Basically a measure of healthy aging. But the main measure of epigenetic age in our study is GrimAge, which was designed around the methylation science associated with lifespan that is time to death. 

[00:10:37] Erin Spain, MS: So let's talk a little bit about what you found in this study. You examined whether cumulative alcohol consumption, which is the number of years that a person consumes beer, liquor, wine, just their total alcohol consumption, as well as the presence of recent binge drinking, with these four measures that you just described. Tell me about the associations that you found. 

[00:10:59] Lifang Hou, MD, PhD, MS: So our study found that accumulative alcohol consumption overall and of liquor specifically both influence epigenetic age. On the other hand, binge drinking may only have more short-term effects. Of course, this is only based on the CARDIA study. More studies are needed. Additionally, we also observed individuals who are younger in age exhibited greater epigenetic age compared to older individuals suggesting chronological age in the setting of alcohol consumption may affect aging differently. The picture is less clear concerning beer and wine specifically, but that just means there is more work to do yet. 

[00:11:47] Erin Spain, MS: So this may be concerning for folks that do drink on a somewhat regular basis. Tell me, do you think it's possible to reverse this aging as a result of alcohol consumption? Is this something that you're interested in looking in further? 

[00:12:01] Lifang Hou, MD, PhD, MS: It is possible and several studies have identified healthy lifestyle behaviors can result in younger epigenetic age. However, these are mainly observational studies, meaning that they only examined epigenetic age at one time point. What we really want to do is to look the cumulative exposure in relation to epigenetic changes in a prospective way or longitudinal setting to understand the dynamics of epigenetic change. We still have lot of work to do on whether epigenetic age can be deliberately altered. We will also need the clinical trials, and we need to know how quickly epigenetic age can be changed in response to lifestyle changes or any intervention. So additionally, studies exploring whether alcohol cessation will reduce the accelerated epigenetic aging caused by alcohol compared to individuals who continue to drink is additional area of interest. 

[00:13:12] Erin Spain, MS: Based on what you saw in this study with the CARDIA participants, would you say that there is an okay amount of alcohol for people to drink that doesn't impact their epigenetic aging? 

[00:13:23] Lifang Hou, MD, PhD, MS: This is a very difficult question because this is only based on one study. The optimal study design would be conducting relatively healthy individuals to avoid any reverse causality by any disease because epigenetic age can be also accelerated by any existing diseases. CARDIA is an ideal study for us to study any risk factors that may affect our biological aging process. However, we also need validation seeing other studies that are well designed with similar risk exposure measurement and also disease outcomes. So that is what we are working on. Hopefully we will have some optimal promising results for us to report. 

[00:14:17] Erin Spain, MS: What is sort of the consensus in the health community, in the medical community about alcohol consumption? What is safe or is any amount of alcohol safe? 

[00:14:28] Lifang Hou, MD, PhD, MS: The results on the effect of alcohol on human health has been conflicting. I think one of the reason is that we don't have a accurate assessment on the adverse effect of alcohol. More studies, longitudinal studies are needed to really study the long-term effect of alcohol on health on different diseases. This kind of studies in general requires a large cohort, requires decades of follow-up to have sufficient numbers for certain diseases. So this is one of the reasons that so far the results have not been consistent. More studies, are needed. And that's one of, areas we have been focusing on. 

[00:15:18] Erin Spain, MS: Much of your work has to do with cancer epidemiology. Do these findings correlate to a relationship between alcohol and cancer development as well in this context? 

[00:15:29] Lifang Hou, MD, PhD, MS: So far, except for liver cancer, alcohol has not been clearly linked with any cancer development. Scientific evidence does show some biological changes induced by alcohol associated with cancer development. More studies are needed. More solid evidence are needed if alcohol really cause cancer or have a carcinogenic role. 

[00:15:56] Erin Spain, MS: Northwestern University Feinberg School of Medicine is very interested in learning more about aging and how to extend life. And this study that was published in the journal Aging is very much connected to that goal. Tell me broadly about some of the work being done at Northwestern to address aging and chronic diseases and chronic disease prevention. 

[00:16:18] Lifang Hou, MD, PhD, MS: Many scientists in our medical school are studying aging. Not only brain aging, but other aging related diseases. Our group of folks are study how molecular aging can be accurately measured and what are the causes of molecular aging. How molecular aging study can guide us in finding tools or biomarkers that guided aging disease prevention. One of the aging biomarkers, molecular aging, that's what we have been focusing on, we still have a lot of work to do in addition to our current study on epigenetic aging. So I think it's very important to let the patients know what bad things is happening in their system and how diseases will affect their life that they want to live. So this is our work to find the biomarkers that provide some biological information or evidence to show patients or physicians that things are already happening. We need to do something and to stop it before it's too late. Meaning that before the disease has developed. 

[00:17:28] Erin Spain, MS: Well, thank you so much for coming on the show today and explaining this important research, and I'm sure there will be more to come. 

[00:17:35] Lifang Hou, MD, PhD, MS: Thank you for having me. Thank you very much. 

[00:17:37] Erin Spain, MS: Thanks for listening, and be sure to subscribe to this show on Apple Podcasts or wherever you listen to podcasts. And rate and review us also for medical professionals. This episode of Breakthroughs is available for CME credit. Go to our website, Feinberg.Northwestern.edu and search CME.