, Volume 236, Issue 11, pp 3245–3255 | Cite as

Effect of alcohol use disorder on cellular aging

  • Luana Martins de CarvalhoEmail author
  • Corinde E. Wiers
  • Peter Manza
  • Hui Sun
  • Melanie Schwandt
  • Gene-Jack Wang
  • Rodrigo Grassi-Oliveira
  • Ana Lúcia Brunialti Godard
  • Nora D. Volkow
Original Investigation



Human telomeres consist of tandem repeats at chromosome ends which protect chromosomal DNA from degradation. Telomere shortening occurs as part of natural aging; however, life stressors, smoking, drug use, BMI, and psychiatric disorders could disrupt cell aging and affect telomere length (TL). In this context, studies have evaluated the effects of alcohol consumption on TL; however, results have been inconsistent, which may reflect diverse drinking cut-offs and categorizations.


To help clarify this, the present study addresses the association of TL with alcohol use disorder (AUD), drinking behaviors, lifetime stress, and chronological age.


TL was quantified as the telomere to albumin ratio (T/S ratio) obtained from peripheral blood DNA using the quantitative PCR assay, from 260 participants with AUD and 449 non-dependent healthy controls (HC) from an existing National Institute on Alcohol Abuse and Alcoholism (NIAAA) database.


AUD participants showed shorter TL compared to HC with both, age, and AUD, as independent predictors as well as a significant AUD with age interaction effect on TL. TL was also associated with impulsiveness in AUD participants. We did not observe an association between TL and chronicity of alcohol use, alcohol doses ingested, or childhood trauma exposures in either AUD or HC, although very few HC reported a history of childhood trauma.


Our results support previous findings of telomere shortening with chronic alcohol exposures and show both an effect of AUD on TL that is independent of age as well as a significant AUD by age interaction on TL. These findings are consistent with accelerated cellular aging in AUD.


Telomere Stress Alcohol Genetics 



The authors acknowledge the Division of Intramural Clinical and Biological Research, NIAAA, including the 1SE Inpatient Behavioral Health Unit and the 1SE Outpatient Clinic and also thank the participants in the study.

Authors’ contribution

All authors discussed the results and contributed to the final manuscript.


The work was supported by the National Institutes of Health Intramural Research Program and grant number Y1AA-3009 to NDV.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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  1. Aida J, Yokoyama A, Izumiyama N, Nakamura KI, Ishikawa N, Poon SS, Fujiwara M, Sawabe M, Matsuura M, Arai T, Takubo K (2011) Alcoholics show reduced telomere length in the oesophagus. J Pathol 223:410–416. CrossRefPubMedGoogle Scholar
  2. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4 edGoogle Scholar
  3. Asberg M, Montgomery SA, Perris C et al (1978) A comprehensive psychopathological rating scale. Acta Psychiatr Scand Suppl 57:5–27CrossRefGoogle Scholar
  4. Barzilai A, Yamamoto K-I (2004) DNA damage responses to oxidative stress. DNA Repair (Amst) 3:1109–1115. CrossRefGoogle Scholar
  5. Bernstein DP, Fink L, Handelsman L et al (1994) Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry 151:1132–1136. CrossRefPubMedGoogle Scholar
  6. Blackburn EH, Epel ES, Lin J (2015) Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science (80- ) 350:1193–1198. CrossRefGoogle Scholar
  7. Buss AH, Perry M (1992) The aggression questionnaire. J Pers Soc Psychol 63:452–459CrossRefGoogle Scholar
  8. Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cheng GLF, Zeng H, Leung M-K, Zhang HJ, Lau BWM, Liu YP, Liu GX, Sham PC, Chan CCH, So KF, Lee TMC (2013) Heroin abuse accelerates biological aging: a novel insight from telomerase and brain imaging interaction. Transl Psychiatry 3:e260. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Coimbra BM, Carvalho CM, Moretti PN, Mello MF, Belangero SI (2017) Stress-related telomere length in children: a systematic review. J Psychiatr Res 92:47–54. CrossRefPubMedGoogle Scholar
  11. Darrow SM, Verhoeven JE, Révész D, Lindqvist D, Penninx BWJH, Delucchi KL, Wolkowitz OM, Mathews CA (2016) The association between psychiatric disorders and telomere length: a meta-analysis involving 14,827 persons. Psychosom Med 78:776–787. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Farah MJ (2017) The neuroscience of socioeconomic status: correlates, causes, and consequences. Neuron 96:56–71. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Gielen M, Hageman GJ, Antoniou EE, Nordfjall K, Mangino M, Balasubramanyam M, de Meyer T, Hendricks AE, Giltay EJ, Hunt SC, Nettleton JA, Salpea KD, Diaz VA, Farzaneh-Far R, Atzmon G, Harris SE, Hou L, Gilley D, Hovatta I, Kark JD, Nassar H, Kurz DJ, Mather KA, Willeit P, Zheng YL, Pavanello S, Demerath EW, Rode L, Bunout D, Steptoe A, Boardman L, Marti A, Needham B, Zheng W, Ramsey-Goldman R, Pellatt AJ, Kaprio J, Hofmann JN, Gieger C, Paolisso G, Hjelmborg JBH, Mirabello L, Seeman T, Wong J, van der Harst P, Broer L, Kronenberg F, Kollerits B, Strandberg T, Eisenberg DTA, Duggan C, Verhoeven JE, Schaakxs R, Zannolli R, dos Reis RMR, Charchar FJ, Tomaszewski M, Mons U, Demuth I, Iglesias Molli AE, Cheng G, Krasnienkov D, D'Antono B, Kasielski M, McDonnell BJ, Ebstein RP, Sundquist K, Pare G, Chong M, Zeegers MP, TELOMAAS group (2018) Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies. Am J Clin Nutr 108:453–475. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Glass D, Parts L, Knowles D, Aviv A, Spector TD (2010) No correlation between childhood maltreatment and telomere length. Biol Psychiatry 68:e21–e22; author reply e23-4. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hägg S, Zhan Y, Karlsson R et al (2017) Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. C Martin-Ruiz 16:e1100. CrossRefGoogle Scholar
  16. Hanssen LM, Schutte NS, Malouff JM, Epel ES (2017) The relationship between childhood psychosocial stressor level and telomere length: a meta-analysis. Heal Psychol Res 5:6378. CrossRefGoogle Scholar
  17. Harpaz T, Abumock H, Beery E et al (2018) The effect of ethanol on telomere dynamics and regulation in human cells. Cells 7:169. CrossRefPubMedCentralGoogle Scholar
  18. Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO (1991) The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br J Addict 86:1119–1127CrossRefGoogle Scholar
  19. Järvelä-Reijonen E, Karhunen L, Sairanen E, Rantala S, Laitinen J, Puttonen S, Peuhkuri K, Hallikainen M, Juvonen K, Myllymäki T, Föhr T, Pihlajamäki J, Korpela R, Ermes M, Lappalainen R, Kolehmainen M (2016) High perceived stress is associated with unfavorable eating behavior in overweight and obese Finns of working age. Appetite 103:249–258. CrossRefPubMedGoogle Scholar
  20. Kang JI, Hwang SS, Choi JR, Lee ST, Kim J, Hwang IS, Kim HW, Kim CH, Kim SJ (2017) Telomere length in alcohol dependence: a role for impulsive choice and childhood maltreatment. Psychoneuroendocrinology 83:72–78. CrossRefPubMedGoogle Scholar
  21. Kim SW, Wiers CE, Tyler R, Shokri-Kojori E, Jang YJ, Zehra A, Freeman C, Ramirez V, Lindgren E, Miller G, Cabrera EA, Stodden T, Guo M, Demiral ŞB, Diazgranados N, Park L, Liow JS, Pike V, Morse C, Vendruscolo LF, Innis RB, Koob GF, Tomasi D, Wang GJ, Volkow ND (2018) Influence of alcoholism and cholesterol on TSPO binding in brain: PET [11C]PBR28 studies in humans and rodents. Neuropsychopharmacology 43:1832–1839. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Küffer AL, O’Donovan A, Burri A, Maercker A (2016) Posttraumatic stress disorder, adverse childhood events, and buccal cell telomere length in elderly Swiss former indentured child laborers. Front Psychiatry 7:147. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Latifovic L, Peacock SD, Massey TE, King WD (2016) The influence of alcohol consumption, cigarette smoking, and physical activity on leukocyte telomere length. Cancer Epidemiol Biomark Prev 25:374–380. CrossRefGoogle Scholar
  24. Levandowski ML, Tractenberg SG, de Azeredo LA, de Nardi T, Rovaris DL, Bau CHD, Rizzo LB, Maurya PK, Brietzke E, Tyrka AR, Grassi-Oliveira R (2016) Crack cocaine addiction, early life stress and accelerated cellular aging among women. Prog Neuro-Psychopharmacol Biol Psychiatry 71:83–89. CrossRefGoogle Scholar
  25. Li Z, He Y, Wang D, Tang J, Chen X (2017) Association between childhood trauma and accelerated telomere erosion in adulthood: a meta-analytic study. J Psychiatr Res 93:64–71. CrossRefPubMedGoogle Scholar
  26. Li J, Guan Y, Akhtar F et al (2018) The Association between Alcohol Consumption and Telomere Length: A Meta-Analysis Focusing on Observational Studies. bioR xiv:374280. CrossRefGoogle Scholar
  27. Liu X, Bao G, Huo T, Wang Z, He X, Dong G (2009) Constitutive telomere length and gastric cancer risk: case-control analysis in Chinese Han population. Cancer Sci 100:1300–1305. CrossRefPubMedGoogle Scholar
  28. Liu J, Yang Y, Zhang H, Zhao S, Liu H, Ge N, Yang H, Xing JL, Chen Z (2011) Longer leukocyte telomere length predicts increased risk of hepatitis B virus-related hepatocellular carcinoma: a case-control analysis. Cancer 117:4247–4256. CrossRefPubMedGoogle Scholar
  29. Marcon F, Siniscalchi E, Andreoli C, Allione A, Fiorito G, Medda E, Guarrera S, Matullo G, Crebelli R (2017) Telomerase activity, telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits. Environ Mol Mutagen 58:551–559. CrossRefPubMedGoogle Scholar
  30. Norbeck JS (1984) Modification of life event questionnaires for use with female respondents. Res Nurs Health 7:61–71CrossRefGoogle Scholar
  31. Olivieri F, Albertini MC, Orciani M, Ceka A, Cricca M, Procopio AD, Bonafè M (2015) DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging. Oncotarget 6:35509–35521. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Olovnikov AM (1973) A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41:181–190CrossRefGoogle Scholar
  33. Pavanello S, Hoxha M, Dioni L, Bertazzi PA, Snenghi R, Nalesso A, Ferrara SD, Montisci M, Baccarelli A (2011) Shortened telomeres in individuals with abuse in alcohol consumption. Int J Cancer 129:983–992. CrossRefPubMedPubMedCentralGoogle Scholar
  34. Reichert S, Stier A (2017) Does oxidative stress shorten telomeres in vivo ? A review. Biol Lett 13:20170463. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Ridout KK, Levandowski M, Ridout SJ, Gantz L, Goonan K, Palermo D, Price LH, Tyrka AR (2018) Early life adversity and telomere length: a meta-analysis. Mol Psychiatry 23:858–871. CrossRefPubMedGoogle Scholar
  36. Rom O, Reznick AZ (2015) The stress reaction: a historical perspective. In: Advances in experimental medicine and biology, pp 1–4Google Scholar
  37. Sanders B, Becker-Lausen E (1995) The measurement of psychological maltreatment: early data on the child abuse and trauma scale. Child Abuse Negl 19:315–323CrossRefGoogle Scholar
  38. Saunders JB, Aasland OG, Babor TF et al (1993) Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II. Addiction 88:791–804CrossRefGoogle Scholar
  39. Savage SA, Bertuch AA (2010) The genetics and clinical manifestations of telomere biology disorders. Genet Med 12:753–764. CrossRefPubMedGoogle Scholar
  40. Shin C, Baik I (2016) Associations between alcohol consumption and leukocyte telomere length modified by a common polymorphism of ALDH2. Alcohol Clin Exp Res 40:765–771. CrossRefPubMedGoogle Scholar
  41. Skinner HA, Allen BA (1982) Alcohol dependence syndrome: measurement and validation. J Abnorm Psychol 91:199–209CrossRefGoogle Scholar
  42. Skinner HA, Sheu WJ (1982) Reliability of alcohol use indices. The lifetime drinking history and the MAST. J Stud Alcohol 43:1157–1170. CrossRefPubMedGoogle Scholar
  43. Sobell LC, MB Sobell (1996) Timeline Followback: User’s guide - a calendar method for assessing alcohol and drug use. Toronto Addict Res FoundGoogle Scholar
  44. Strandberg TE, Strandberg AY, Saijonmaa O, Tilvis RS, Pitkälä KH, Fyhrquist F (2012) Association between alcohol consumption in healthy midlife and telomere length in older men. The Helsinki businessmen study. Eur J Epidemiol 27:815–822. CrossRefPubMedGoogle Scholar
  45. Verhoeven JE, Révész D, Epel ES, Lin J, Wolkowitz OM, Penninx BWJH (2014) Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Mol Psychiatry 19:895–901. CrossRefPubMedGoogle Scholar
  46. Victorelli S, Passos JF (2017) Telomeres and cell senescence - size matters not. EBioMedicine 21:14–20. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239:197–201CrossRefGoogle Scholar
  48. Wechsler D (1999) Wechsler abbreviated scale of intelligence. Psychol Corp San Antonio, TXGoogle Scholar
  49. Wei R, DeVilbiss FT, Liu W (2015) Genetic polymorphism, telomere biology and non-small lung Cancer risk. J Genet Genomics 42:549–561. CrossRefPubMedGoogle Scholar
  50. Wellinger RJ (2014) In the end, What’s the problem? Mol Cell 53:855–856. CrossRefPubMedGoogle Scholar
  51. Whiteside SP, Lynam DR (2001) The five factor model and impulsivity: using a structural model of personality to understand impulsivity. Pers Individ Dif 30:669–689. CrossRefGoogle Scholar
  52. World Health Organization (2018) Global status report on alcohol and health 2018,. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-publication. World Health Organization, GenevaGoogle Scholar
  53. Wu D, Cederbaum AI (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 27:277–284PubMedPubMedCentralGoogle Scholar
  54. Yamaki N, Matsushita S, Hara S, Yokoyama A, Hishimoto A, Higuchi S (2019) Telomere shortening in alcohol dependence: roles of alcohol and acetaldehyde. J Psychiatr Res 109:27–32. CrossRefPubMedGoogle Scholar
  55. Yang Z, Ye J, Li C, Zhou D, Shen Q, Wu J, Cao L, Wang T, Cui D, He S, Qi G, He L, Liu Y (2013) Drug addiction is associated with leukocyte telomere length. Sci Rep 3:1542. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Yim O-S, Zhang X, Shalev I, Monakhov M, Zhong S, Hsu M, Chew SH, Lai PS, Ebstein RP (2016) Delay discounting, genetic sensitivity, and leukocyte telomere length. Proc Natl Acad Sci U S A 113:2780–2785. CrossRefPubMedPubMedCentralGoogle Scholar
  57. Zhan Y, Clements MS, Roberts RO, Vassilaki M, Druliner BR, Boardman LA, Petersen RC, Reynolds CA, Pedersen NL, Hägg S (2018) Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies. Neurobiol Aging 69:111–116. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Zhu Y, Liu X, Ding X, Wang F, Geng X (2018) Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction. Biogerontology. 20:1–16. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Luana Martins de Carvalho
    • 1
    • 2
    Email author
  • Corinde E. Wiers
    • 1
  • Peter Manza
    • 1
  • Hui Sun
    • 1
  • Melanie Schwandt
    • 1
  • Gene-Jack Wang
    • 1
  • Rodrigo Grassi-Oliveira
    • 3
  • Ana Lúcia Brunialti Godard
    • 2
  • Nora D. Volkow
    • 4
  1. 1.National Institute on Alcohol Abuse and Alcoholism, National Institutes of HealthBethesdaUSA
  2. 2.Laboratório de Genética Animal e Humana, Departamento de Biologia Geral, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Developmental Cognitive Neuroscience Lab (DCNL), Brain Institute (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  4. 4.National Institute on Drug Abuse, Bethesda, National Institutes of HealthBethesdaUSA

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