Methamphetamine use shortens telomere length in male adults and rats

Abstract

BackgroundMethamphetamine (MA) use increases the risk of age-related diseases. However, it remains uncertain whether MA use exhibits accelerated biological aging, as indicated by telomere length (TL), a proposed marker of aging. Here we conducted studies in both humans and rats to investigate the association between MA use and TL. MethodsWe recruited 125 male MA users and 66 healthy controls, aged 30–40 years. MA users were diagnosed using DSM-5 criteria and categorized into two groups: non-severe (n = 78) and severe (n = 47) MA use disorder (MUD). MA-treated conditioned place preference (CPP) rats were utilized to validate our clinical investigations. TL was assessed using real-time polymerase chain reaction. ResultsAt clinical levels, MA users exhibited significantly shorter leukocyte TL compared to healthy controls. Among MA users, individuals with severe MUD had significantly shorter leukocyte TL than those with non-severe MUD. Importantly, both univariate and multivariate linear regression analyses demonstrated a negative association between the severity of MA use and leukocyte TL. In a rat model of MA-induced CPP, leukocyte TL was also significantly shortened after MA administration, especially in rats with higher CPP expression or reinstatement scores. ConclusionMA use shortened TL, and the severity of MA use was negatively correlated with TL. These findings provide new insights into the pathophysiology of accelerated aging caused by MA use and may have implications for identifying biomarkers and developing novel treatment strategies for MUD.