Shortened leukocyte telomere length in young adults who use methamphetamine

Yen-Feng Lin,Hsing-Cheng Liu,Yi-Lung Chen,Po-Yu Chen,Ming-Chyi Huang,Wei-Hern Chou

doi:10.1038/s41398-021-01640-z

Abstract

Methamphetamine (METH) use, most prevalent in young adults, has been associated with high rates of morbidity and mortality. The relationship between METH use and accelerated biological aging, which can be measured using leukocyte telomere length (LTL), remains unclear. We examined whether young adult METH users have shorter LTL and explored the relationship between characteristics of METH use and LTL by using Mendelian randomization (MR) analysis. We compared the LTL for 187 METH users and 159 healthy individuals aged between 25 and 34 years and examined the relationship of LTL with METH use variables (onset age, duration, and maximum frequency of METH use) by using regression analyses. In addition, 2-stage-least-squares (2SLS) MR was also performed to possibly avoid uncontrolled confounding between characteristics of METH use and LTL. We found METH users had significantly shorter LTL compared to controls. Multivariate regression analysis showed METH use was negatively associated with LTL (β = −0.36, P < .001). Among METH users, duration of METH use was negatively associated with LTL after adjustment (β = −0.002, P = .01). We identified a single nucleotide polymorphism (SNP) rs6585206 genome-wide associated with duration of METH use. This SNP was used as an instrumental variable to avoid uncontrolled confounding for the relationship between the use duration and LTL shortening. In conclusion, we show that young adult METH users may have shorter LTL compared with controls and longer duration of METH use was significantly associated with telomere shortening. These observations suggest that METH use may accelerate biological senescence.

Highlights

Illicit methamphetamine (METH) use leads to considerable public health, legal, and social problems worldwide and contributes substantially to global disease burden, causing a 37% increase in the disability adjusted life years over the past decades [1]
Because adverse childhood experiences (ACEs) have been previously associated with decreased telomere length in people with drug addiction [32, 36], the selfrelationship between METH use and leukocyte telomere length (LTL) and in order to test our hypothesis that METH use will exhibit accelerated cellular senescence as measured by LTL, in this study we first compared the LTLs of young adult METH users and healthy controls
We identified single nucleotide polymorphisms (SNPs) that were associated genome-wide with the METH use variables assessed in this study and performed Mendelian randomization (MR) to possibly avoid uncontrolled confounding between characteristics of METH use and LTL in young adults

Summary

INTRODUCTION

Illicit methamphetamine (METH) use leads to considerable public health, legal, and social problems worldwide and contributes substantially to global disease burden, causing a 37% increase in the disability adjusted life years over the past decades [1]. Shorter LTL has been associated with aging-related diseases such as atherosclerotic cardiovascular diseases [27] as well as increased risks for morbidity and mortality [28]. These observations suggest a link between LTL shortening and METH use. Because adverse childhood experiences (ACEs) have been previously associated with decreased telomere length in people with drug addiction [32, 36], the selfrelationship between METH use and LTL and in order to test our hypothesis that METH use will exhibit accelerated cellular senescence as measured by LTL, in this study we first compared the LTLs of young adult METH users and healthy controls. To assess the relative LTLs of our participants, we performed two separate quantitative polymerase chain reactions (qPCRs) using the StepOnePlusTM

MATERIAL AND METHODS

RESULTS

FUNDING INFORMATION