*For medical professionals only for reference
When it comes to smoking and drinking, it is estimated that the first thing that comes to mind is the three major hobbies of a crosstalk actor: smoking, drinking and perming! Smoking is harmful to health, but in China, where alcohol culture is prevalent, many people believe that drinking moderately is beneficial.
However, a series of studies have shown that moderate drinking is also harmful. For the sake of health, it is better not to stick to alcohol [1-2]! It is reported that 1.78 million people died from alcohol consumption worldwide in 2020, and alcohol consumption is the main risk factor for death among men aged 15–49 [2]. Drinking alcohol can cause many health problems, including cancer, gastrointestinal diseases, cirrhosis, , etc. [2].
However, will drinking affect aging? Very little is known at the moment.
Recently, a research team led by Professor A. Topiwala of the Big Data Institute of Oxford University published important research results in the journal "Molecular Psychiatry" [3].
They analyzed data on alcohol consumption and telomere length in the UK large population cohort - UK biobank, 245,354 participants. They found that higher alcohol intake in participants was significantly associated with shorter telomere lengths. The results of this study show that drinking alcohol may shorten the length of telomeres, and telomeres are closely related to human aging and a variety of age-related diseases. Therefore, from today on, "drinking alcohol harms the body" has another layer of correlation - "premature aging"!
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When it comes to telomeres, everyone will definitely think of the telomeres hypothesis. Telomeres length is considered a potential biological marker of aging [4]. As we age, the telomeres of human cells will wear out, and extremely short telomeres will cause cell death or replicative aging. Epidemiology , the shorter leukocyte telomeres length (LTL) is associated with the development of a variety of age-related diseases, including Alzheimer's disease , cancer and coronary artery disease [5-6]. However, whether alcohol consumption is related to changes in telomere length is still controversial.
To better understand the relationship between alcohol intake and LTL, the researchers conducted the largest analysis to date with the help of relevant data from 245,354 participants in the UK biobank. When recruiting participants at UK biobank, the participants’ drinking situation will be asked about, and the analysis will be classified based on this as the baseline. The researchers used British standards to evaluate the amount of alcohol consumed per week, i.e. 1 unit = 8 grams of ethanol (alcohol). Telomer length was evaluated using participant LTL as baseline.
After analysis, the researchers found that the vast majority of participants were current drinkers, only 8,240 participants never drank, and 9,393 participants had drunk alcohol (Figure 1). Compared with current drinkers, women who never drink are more likely to have higher proportions, lower education, lower smoking rates, and less exercise (Figure 1).
Figure 1 Baseline characteristics of participants
Subsequently, the researchers adjusted for several factors that influence LTL, such as baseline age, gender, education level, smoking, leukocyte count and exercise. The fully adjusted model showed a significant association between high alcohol intake and shorter LTL (Figure 2).
compared with the participants with the lowest alcohol consumption (6 units per week, 48 grams of alcohol), the participants with the highest alcohol consumption (29 units per week, reaching 232 grams) were significantly associated with a significant shortening of telomeres (β=-0.05, p=2.36×10-11). It is worth mentioning that participants diagnosed with alcohol use disorder (AUD) (n = 1301) were associated with shorter LTL compared to the control group (β = -0.15, p = 6.14 × 10 -8 ).
Figure 2 Association of alcohol intake and LTL in participants
To further clarify the impact of alcohol intake on LTL in participants, the researchers conducted Mendelian randomization (MR) analysis on published Genome-wide Association Study (GWAS) data. MR can use genetic variation as an instrumental variable, so the effect of genetic variation in alcohol exposure on telomeres length can be evaluated.
In the GWAS data containing 941,280 people, the investigators selected 93 reported single nucleotide polymorphisms (SNPs) independently associated with participants' alcohol consumption [7] for subsequent analysis. In addition, the researchers also selected 24 reported SNPs related to AUD [8].
researchers used univariate linear MR to find that the genetically predicted alcohol intake in participants was significantly associated with telomere shortening (inverse variance weighted (IVW) β =-0.073, p =0.026, Figure 3). Similar results were obtained in participants diagnosed with AUD (IVWβ=-0.068, p=0.001, Figure 3). After adjusting for factors such as smoking and physical activity, multivariable MR analysis still showed that genetically predicted alcohol intake and telomere shortening was significantly associated (IVWβ =-0.071, p =0.031, Figure 3). Similar results were also obtained among participants in AUD (IVWβ=-0.07, p=0.005, Fig. 3). This result suggests that higher genetically predicted alcohol intake for is associated with shorter telomere lengths.
Figure 3 MR analysis of the association between genetic variation of alcohol intake and AUD and telomeres length
In nonlinear MR analysis, the association of genetically predicted alcohol intake with shortened telomeres length was only significant in people with weekly intakes of more than 17 units (alcohol consumption: 17-28 units, IVWβ=-0.169, p=0.013; alcohol consumption: more than 28 units, IVWβ=-0.2, p=0.046) (Figure 4). This result indicates that there may be a threshold for the effect of alcohol intake on telomere length.
Figure 4 Nonlinear MR analysis of different alcohol consumption populations, genetically predicted alcohol intake and telomere length
Researchers also found that genetically predicted alcohol consumption is significantly correlated with shortening of telomere length (IVWβ=-0.079, p=0.032). This association was not observed in those who never drank (IVWβ=0.001, p=0.91) and those who once drank (IVWβ=-0.004, p=0.71) (Fig. 5).
In addition, it is also observed in current drinkers that genetically predicted AUD and telomere shortening are associated (IVWβ=-0.10, p 0.0001). Non-drinking drinkers and previous drinkers were found.
Figure 5 Nonlinear MR analysis of different drinking habits populations, genetically predicted alcohol intake and telomere length
In summary, this study shows that high alcohol consumption in people is significantly correlated with shorter telomere length, so drinking may promote aging. MR analysis further pointed out that there is a causal relationship between alcohol traits and shortening of telomere length in the population, which is more obvious in the AUD population. In addition, the intake of alcohol is important – even reducing alcohol consumption can be beneficial.
This study also has several limitations. First, the population telomeres length is only characterized by leukocyte samples, and there may be errors. Secondly, the telomere length of the research population was tested only once, and the more perfect experimental design was to monitor the changes in telomere length in populations at different time points, which would be more convincing. Furthermore, participants included in the study were European populations and the results may not be applicable to other ethnic groups. As an observational study of , this study cannot establish a causal relationship, and more research is needed in the future to verify relevant findings.
After reading this article, I think that drinking is not pleasant, and moderate is also harmful to the body!
References:
[1] GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet. 2018 Sep 29;392(10153):1116] [published correction appears in Lancet. 2019 Jun 22;393(10190):e44]. Lancet. 2018;392(10152):1015-1035. doi:10.1016/S0140-6736(18)31310-2
[2] GBD 2020 Alcohol Collaborators. Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020 [published correction appears in Lancet. 2022 Jul 30;400(10349):358]. Lancet. 2022;400(10347):185-235. doi:10.1016/S0140-6736(22)00847-9
[3] Topiwala A, Taschler B, Ebmeier KP, et al. Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects [published online ahead of print, 2022 Jul 26]. Mol Psychiatry. 2022;10.1038/s41380-022-01690-9. doi:10.1038/s41380-022-01690-9
[4] Vaiserman A, Krasnienkov D. Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives. Front Genet. 2021;11:630186. Published 2021 Jan 21. doi:10.3389/fgene.2020.630186
[5] Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, et al. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncol. 2017;3(5):636-651. doi:10.1001/jamaoncol.2016.5945
[6] Scheller Madrid A, Rasmussen KL, Rode L, Frikke-Schmidt R, Nordestgaard BG, Bojesen SE. Observational and genetic studies of short telomeres and Alzheimer's disease in 67,000 and 152,000 individuals: a Mendelian randomization study. Eur J Epidemiol. 2020;35(2):147-156. doi:10.1007/s10654-019-00563-w
[7] Liu M, Jiang Y, Wedow R, et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etology of tobacco and alcohol use. Nat Genet. 2019;51(2):237-244. doi:10.1038/s41588-018-0307-5
[8] Zhou H, Sealock JM, Sanchez-Roige S, et al. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nat Neurosci. 2020;23(7):809-818. doi:10.1038/s41593-020-0643-5
Editor in charge｜Tan Shuo
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