Black Americans with sickle cell disease (SCD) demonstrate accelerated epigenetic pace of aging compared to Black Americans without SCD.

Melanie E Garrett, Brandon Le, Kyle J Bourassa, Michelle F Dennis, Daniel Hatch, Qing Yang, Paula Tanabe, Nirmish Shah, Faith S Luyster, Charity Oyedeji, John J Strouse, Harvey J Cohen, Nathan A Kimbrel, Jean C Beckham, Mitchell R Knisely, Marilyn J Telen, Allison E Ashley-Koch
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Abstract

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 to 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 to the veterans without SCD, whereby SCD patients were aging approximately 0.7 months more per year than those without SCD (p=4.49x10-8). 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 PTSD from the non-SCD group (p=2.18x10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p=1.61x10-10).

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.

与没有镰状细胞病(SCD)的美国黑人相比,患有镰状细胞病(SCD)的美国黑人的表观遗传学衰老速度加快。
背景:镰状细胞病(SCD)是一种慢性疾病,其特点是红细胞镰状化、血管闭塞、溶血性贫血,随后导致终末器官损伤和存活率降低。由于这种重要的病理生理学特征和早期死亡率,我们假设与非 SCD 患者相比,SCD 患者正经历着加速的生物衰老:我们使用 DunedinPACE 测量方法比较了 131 名患有 SCD 的美国黑人和 1391 名未患有 SCD 的美国黑人退伍军人的表观遗传学衰老速度:结果:与未患 SCD 的退伍军人相比,SCD 患者的衰老速度明显加快(DunedinPACE 平均差值为 0.057 分),SCD 患者比未患 SCD 的退伍军人每年多衰老约 0.7 个月(p=4.49x10-8)。尽管 SCD 患者的实际年龄明显小于非 SCD 患者,但这一情况仍然存在,这使得表观遗传衰老差异更加明显。当我们把患有创伤后应激障碍的人从非SCD组中剔除时,这种关联变得更强(p=2.18x10-9);当我们把SCD患者限制在血红蛋白SS和Sβ0地中海贫血基因型的人时,这种关联变得更强(p=1.61x10-10):这些数据支持了我们的假设,即通过全球表观遗传变异来衡量,SCD 患者的生物衰老加速。对生物衰老的表观遗传学测量进行评估可能有助于确定哪些 SCD 患者最受益于临床干预措施以降低死亡率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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