Pain Research & Intervention Center of Excellence (PRICE), University of Florida, Gainesville, FL, USA.
Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA.
Epigenetics. 2022 Dec;17(13):2178-2187. doi: 10.1080/15592294.2022.2111752. Epub 2022 Aug 17.
Chronic musculoskeletal pain is a health burden that may accelerate the aging process. Accelerated brain aging and epigenetic aging have separately been observed in those with chronic pain. However, it is unknown whether these biological markers of aging are associated with each other in those with chronic pain. We aimed to explore the association of epigenetic aging and brain aging in middle-to-older age individuals with varying degrees of knee pain. Participants (57.91 ± 8.04 y) with low impact knee pain (n = 95), high impact knee pain (n = 53), and pain-free controls (n = 26) completed self-reported pain, a blood draw, and an MRI scan. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), the subsequent difference of predicted epigenetic and brain age from chronological age (DNAmGrimAge-Difference and Brain-PAD, respectively). There was a significant main effect for pain impact group ( (2,167) = 3.847, = 0.023, = 0.038, ANCOVA) on Brain-PAD and DNAmGrimAge-difference ( (2,167) = 6.800, = 0.001, = 0.075, ANCOVA) after controlling for covariates. DNAmGrimAge-Difference and Brain-PAD were modestly correlated ( =0.198; =0.010). Exploratory analysis revealed that DNAmGrimAge-difference mediated GCPS pain impact, GCPS pain severity, and pain-related disability scores on Brain-PAD. Based upon the current study findings, we suggest that pain could be a driver for accelerated brain aging via epigenome interactions.
慢性肌肉骨骼疼痛是一种健康负担，可能会加速衰老过程。在患有慢性疼痛的人群中，分别观察到大脑加速衰老和表观遗传衰老。然而，尚不清楚这些衰老的生物学标志物在慢性疼痛患者中是否相互关联。我们旨在探讨不同程度膝关节疼痛的中老年个体中表观遗传衰老和大脑衰老之间的相关性。参与者（57.91 ± 8.04 岁）中，低影响膝关节疼痛组（n = 95）、高影响膝关节疼痛组（n = 53）和无痛对照组（n = 26）完成了自我报告的疼痛、血液采集和 MRI 扫描。我们使用了先前与膝关节疼痛相关的表观遗传时钟（DNAmGrimAge），以及随后的预测表观遗传年龄和大脑年龄与实际年龄的差异（DNAmGrimAge-Difference 和 Brain-PAD）。疼痛影响组（ (2,167) = 3.847, = 0.023, = 0.038, ANOVA）对 Brain-PAD 和 DNAmGrimAge-difference 有显著的主效应（ (2,167) = 6.800, = 0.001, = 0.075, ANOVA），在控制了协变量后。DNAmGrimAge-Difference 和 Brain-PAD 之间存在适度相关性（ =0.198; =0.010）。探索性分析表明，DNAmGrimAge-difference 介导了 GCPS 疼痛影响、GCPS 疼痛严重程度和与疼痛相关的残疾评分对 Brain-PAD 的影响。基于目前的研究结果，我们认为疼痛可能通过表观基因组的相互作用成为加速大脑衰老的驱动因素。
