Department of Neurosciences, University of California San Diego, San Diego, CA, USA; Rady Children's Hospital San Diego, San Diego, CA, USA.
Department of Neurosciences, University of California San Diego, San Diego, CA, USA; Boston University, Boston, CA, USA.
Mult Scler Relat Disord. 2024 Apr;84:105498. doi: 10.1016/j.msard.2024.105498. Epub 2024 Feb 11.
Telomere attrition is associated with disability accumulation and brain atrophy in multiple sclerosis (MS). Downstream of telomere attrition is cellular senescence. We sought to determine differences in the cellular senescence marker p16INK4a expression between MS and healthy control participants and the association of p16INK4a expression with MS disability and treatment exposure.
Patients meeting diagnostic criteria for MS and healthy controls were recruited for a cross-sectional pilot study. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and p16INK4a expression levels were measured using qRT PCR. Spearman correlation coefficients and regression models were applied to compare expression levels to chronological age, assess case control differences, and determine associations with clinical outcome measures.
Fifty-two participants with MS (67 % female, ages 25-70) and 38 healthy controls (66 % female, ages 23-65) were included. p16INK4a levels were not linearly correlated with chronological age in MS (rho = -0.01, p = 0.94) or control participants (rho = 0.02, p = 0.92). Higher median p16INK4a levels were observed in the >50-year age group for MS (0.25, IQR 0.14-0.35) vs. controls (0.12, IQR 0.05-0.15) and in this age group B cell depletion therapy was associated with lower expression levels. p16INK4a expression was not associated with any of the measured MS disability outcomes.
Caution is needed with using p16INK4a expression level from PBMCs as an aging biomarker in MS participants, given lack of correlation with chronological age or large associations with clinical outcomes.
端粒磨损与多发性硬化症（MS）中的残疾积累和脑萎缩有关。端粒磨损的下游是细胞衰老。我们试图确定 MS 患者和健康对照参与者之间细胞衰老标志物 p16INK4a 表达的差异，以及 p16INK4a 表达与 MS 残疾和治疗暴露的相关性。
符合 MS 诊断标准的患者和健康对照者被招募进行横断面试点研究。从外周血单核细胞（PBMC）中提取 RNA，并使用 qRT-PCR 测量 p16INK4a 表达水平。采用 Spearman 相关系数和回归模型比较表达水平与实际年龄，评估病例对照差异，并确定与临床结局测量的相关性。
52 名 MS 患者（67%为女性，年龄 25-70 岁）和 38 名健康对照者（66%为女性，年龄 23-65 岁）被纳入研究。p16INK4a 水平与 MS（rho=-0.01，p=0.94）或对照参与者（rho=0.02，p=0.92）的实际年龄无线性相关。在 MS 中，>50 岁年龄组的中位数 p16INK4a 水平更高（0.25，IQR 0.14-0.35），而对照组为（0.12，IQR 0.05-0.15），且在该年龄组中，B 细胞耗竭疗法与较低的表达水平相关。p16INK4a 表达与任何测量的 MS 残疾结局均无关联。
鉴于 p16INK4a 表达水平与实际年龄缺乏相关性或与临床结局存在较大关联，因此在 MS 参与者中使用 PBMC 中的 p16INK4a 表达水平作为衰老生物标志物时需谨慎。
