Telomeres are repetitive DNA sequences that cap the end of chromosomes, protecting them from damage. Telomere length is considered a potential biological marker of aging. Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. Determining the connection between the two has been challenging due to the lack of reliable methods.

Now, scientists from Oxford Population Health, in a new study, offered evidence that alcohol directly accelerates aging by damaging DNA in telomeres.

Telomeres that are too short prevent cells from dividing and may even cause them to die. Shorter telomeres have been associated with Alzheimer’s, cancer, and coronary artery disease, among other aging-related disorders.

In this study, scientists studied the association between alcohol intake and telomere length in over 245,000 participants in the UK Biobank. Using a genetic approach called Mendelian Randomisation (MR) to determine the effects of alcohol on aging.

This is the first time this method has been used to determine the association between alcohol intake and aging. The approach uses ‘genetic proxies’ to predict each participant’s exposure level.

Scientists used genetic variants previously associated with alcohol consumption and alcohol use disorders in large-scale genome-wide association studies. Based on the subjects’ self-reported weekly alcohol intake at recruitment, the scientists also conducted an observational assessment to supplement the MR analysis.

The observational analysis revealed a significant association between high alcohol intake and shorter telomere length. Compared with drinking less than 6 units of alcohol a week (about two large 250ml glasses of wine), drinking more than 29 units weekly (about ten 250ml glasses of 14% alcohol by volume wine) was associated with between one and two years of age-related change on telomere length.

Individuals diagnosed with an alcohol use disorder had significantly shorter telomere lengths than controls, equivalent to between 3 and 6 years of age-related change.

Similarly, in the MR study, shorter telomere length was linked to higher genetically predicted alcohol use. An increase in weekly consumption from 10 to 32 units was associated with 3 years of aging.

Only those who drank more than 17 units per week showed a significant correlation between telomere length and genetically predicted alcohol use. This implies that telomere degradation may require a minimum level of alcohol use.

The telomere length, comparable to about three years of aging, and genetically predicted alcohol use disorder were also significantly correlated in the MR study.

Most participants were current drinkers, with only 3% being never drinkers and 4% being previous drinkers. 51% were men, 49% were women, and the average age was 57.

Study lead Dr. Anya Topiwala from Oxford Population Health said: “These findings support the suggestion that alcohol, particularly at excessive levels, directly affects telomere length. Shortened telomeres have been proposed as risk factors that may cause several severe age-related diseases, such as Alzheimer’s. Our results provide another piece of information for clinicians and patients seeking to reduce the harmful effects of excess alcohol. Furthermore, the dose of alcohol is important – even reducing drinking could have benefits.”

For both analyses, scientists measured telomere lengths using leucocytes (immune system cells) from the participants’ DNA samples. Participants’ DNA samples were collected during recruitment to the UK Biobank.

In the MR analysis, alcohol intake was estimated by screening DNA samples for 93 genetic variants that have previously been associated with weekly alcohol consumption, besides 24 variants that have previously been linked to a diagnosis of an alcohol use disorder. Because these genetic variants are randomly allocated and fixed before birth, the results give greater confidence that alcohol directly affects telomere length, rather than a different factor is responsible.

Although these results do not conclusively prove that alcohol directly affects telomere length, two studies’ findings support this. 1) Effects were only found in current drinkers and no previous or never-drinkers; 2) The most influential genetic variant in the MR analysis was AD1HB, an alcohol metabolism gene.

Dr. Richard Piper, Chief Executive of Alcohol Change UK, said: “We welcome all research into the effects of alcohol on the human body. This study shows clear links between consuming alcohol and aging and points towards a possible link between alcohol and Alzheimer’s. The researchers are transparent that this study does not prove a causal link, but they also make a well-argued case about the likely biological mechanism. In general, there is an ever-larger body of science showing how alcohol causes so much ill-health and so many early deaths.”

The research team hypothesizes that increased oxidative stress and inflammation may be a biological basis for how alcohol affects telomere length. The body’s metabolism of ethanol has the potential to both increase levels of reactive oxidative species that harm DNA and decrease levels of antioxidant molecules that counteract oxidative stress.

Journal Reference:

  1. Topiwala, A., Taschler, B., Ebmeier, K.P. et al. Alcohol consumption, and telomere length: Mendelian randomization clarifies alcohol’s effects. Mol Psychiatry (2022). DOI: 10.1038/s41380-022-01690-9