There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown. In this study, we evaluated multiple epigenetic clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBlood, DNAmPhenoAge, DNAmGrimAge, and DNAmTL) in individuals with SUD (n = 42), including alcohol (n = 10), opioid (n = 19), and stimulant use disorder (n = 13), and controls (n = 10) in postmortem brain (prefrontal cortex) and blood tissue obtained from the same individuals. We found a higher DNAmPhenoAge (β = 0.191, p-value = 0.0104) and a nominally lower DNAmTL (β = −0.149, p-value = 0.0603) in blood from individuals with SUD compared to controls. SUD subgroup analysis showed a nominally lower brain DNAmTL in subjects with alcohol use disorder, compared to stimulant use disorder and controls (β = 0.0150, p-value = 0.087). Cross-tissue analyzes indicated a lower blood DNAmTL and a higher blood DNAmAge compared to their respective brain values in the SUD group. This study highlights the relevance of tissue specificity in biological aging studies and suggests that peripheral measures of epigenetic clocks in SUD may depend on the specific type of drug used.

中文翻译：

---

在物质使用障碍死后大脑和血液中表观遗传时钟的受试者跨组织分析

患有物质使用障碍 (SUD) 的患者可能会加速生物衰老。表观遗传时钟的评估是基于 DNA 甲基化变化的生物衰老的准确估计，其评估仅限于 SUD 患者的血液组织。因此，生物衰老对 SUD 患者大脑的影响仍然未知。在这项研究中，我们评估了患有 SUD（ n = 42）的个体的多个表观遗传时钟（DNAmAge、DNAmAgeHannum、DNAmAgeSkinBlood、DNAmPhenoAge、DNAmGrimAge 和 DNAmTL） ，包括酒精（n  = 10）、阿片类药物（n  = 19）和兴奋剂使用障碍（n  = 13）和控制（n = 10) 在死后大脑（前额叶皮层）和从同一个人获得的血液组织中。我们发现，与对照组相比，患有 SUD 的个体血液中的 DNAmPhenoAge（ β  = 0.191，p值 = 0.0104）和名义上较低的 DNAmTL（β  = −0.149，p值 = 0.0603）。SUD 亚组分析显示，与兴奋剂使用障碍和对照组相比，酒精使用障碍受试者的大脑 DNAmTL 名义上较低（β  = 0.0150，p-值 = 0.087）。跨组织分析表明，与 SUD 组中各自的脑值相比，血液 DNAmTL 较低，血液 DNAmAge 较高。这项研究强调了组织特异性在生物衰老研究中的相关性，并表明 SUD 中表观遗传时钟的外围测量可能取决于所用药物的具体类型。