BACKGROUND Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD. METHODS We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. RESULTS SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p = 4.49 × 10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p = 2.18 × 10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p = 1.61 × 10-10). CONCLUSIONS These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

中文翻译：

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与没有 SCD 的美国黑人相比，患有镰状细胞病 （SCD） 的美国黑人表现出更快的表观遗传衰老速度。


背景 镰状细胞病 （SCD） 是一种慢性疾病，其特征是红细胞镰状化、血管闭塞、溶血性贫血，随后是终末器官损伤和生存率降低。由于这种重要的病理生理学和早期死亡率，我们假设与没有 SCD 的个体相比，SCD 患者正在经历加速的生物衰老。方法 我们利用 DunedinPACE 测量法比较了 131 名患有 SCD 的美国黑人和 1391 名没有 SCD 的美国黑人退伍军人的表观遗传衰老速度。结果 与没有 SCD 的退伍军人相比，SCD 患者的衰老速度显着加快 （DunedinPACE 平均差异为 0.057 分），其中 SCD 患者的年衰老时间比没有 SCD 的患者多 ≈0.7 个月 （p = 4.49 × 10-8）。这是真的，尽管根据实际年龄，SCD 患者明显比没有 SCD 的个体年轻，这使得表观遗传衰老差异更加明显。当我们从非 SCD 组中去除创伤后应激障碍个体时 （p = 2.18 × 10-9），当我们将 SCD 患者限制为血红蛋白 SS 和 Sβ0 地中海贫血基因型 （p = 1.61 × 10-10） 时，这种关联变得更强。结论 这些数据支持我们的假设，即 SCD 患者通过整体表观遗传变异来衡量，生物衰老加速。对生物衰老的表观遗传学测量的评估可能有助于确定哪些 SCD 患者最能从降低死亡率的临床干预中受益。