Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, The Alfred Hospital, Melbourne, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
Mult Scler Relat Disord. 2024 Jun;86:105607. doi: 10.1016/j.msard.2024.105607. Epub 2024 Apr 10.
Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL.
This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history.
We extracted DNA from the whole blood of 501 people with MS in Melbourne, Australia. Expanded Disability Status Scale (EDSS) score and demographic data, as well as pregnancy history for 197 females, were obtained at sample collection. Additional data were extracted from the MSBase Registry. LTL was determined in base pairs (bp) using real-time quantitative polymerase chain reaction.
A relationship between EDSS score and shorter LTL was robust to multivariable adjustment for demographic and clinical factors including chronological age, with an adjusted LTL reduction per 1.0 increase in EDSS of 97.1 bp (95 % CI = 9.7-184.5 bp, p = 0.030). Adjusted mediation analysis found chronological age accounted for 33.6 % of the relationship between LTL and EDSS score (p = 0.018). In females with pregnancy data, history of pregnancy was associated with older age (median 49.7 vs 33.0 years, p < 0.001). There were no significant relationships between adjusted LTL and any history of pregnancy (LTL increase of 65.3 bp, 95 % CI = -471.0-601.5 bp, p = 0.81) or number of completed pregnancies (LTL increase of 14.6 bp per pregnancy, 95 % CI = -170.3-199.6 bp, p = 0.87).
The correlation between LTL and disability independent of chronological age and other factors points to a link between neurological reserve in MS and biological aging, and a potential research target for pathophysiological and therapeutic mechanisms. Although LTL did not significantly differ by pregnancy history, longitudinal analyses could help identify interactions with prospectively captured pregnancy effects.
衰老相关过程导致多发性硬化症（MS）的神经退行性变和残疾。白细胞端粒长度（LTL）等生物衰老的生物标志物可以帮助对预后进行个性化预测。已经表明妊娠对 MS 女性的残疾累积具有保护作用，尽管尚不清楚这种作用是否与衰老机制或 LTL 相关。
本研究旨在对 MS 患者队列中的 LTL 进行横断面描述，并将 LTL 与残疾严重程度和妊娠史相关联。
我们从澳大利亚墨尔本的 501 名 MS 患者的全血中提取了 DNA。在样本采集时获得了扩展残疾状况量表（EDSS）评分和人口统计学数据，以及 197 名女性的妊娠史。从 MSBase 注册表中提取了其他数据。使用实时定量聚合酶链反应（PCR）以碱基对（bp）确定 LTL。
EDSS 评分与 LTL 缩短之间的关系在经过多变量调整后仍然存在，这些调整因素包括人口统计学和临床因素，如年龄，EDSS 每增加 1.0 分，LTL 缩短 97.1bp（95%CI=9.7-184.5bp，p=0.030）。调整后的中介分析发现，年龄占 LTL 与 EDSS 评分之间关系的 33.6%（p=0.018）。在有妊娠数据的女性中，妊娠史与年龄较大相关（中位数 49.7 岁与 33.0 岁，p<0.001）。调整后的 LTL 与任何妊娠史之间均无显著关系（妊娠后 LTL 增加 65.3bp，95%CI=-471.0-601.5bp，p=0.81）或完成妊娠次数（每完成一次妊娠，LTL 增加 14.6bp，95%CI=-170.3-199.6bp，p=0.87）。
LTL 与残疾之间的相关性独立于年龄和其他因素，这表明 MS 中的神经储备与生物衰老之间存在联系，这可能是病理生理和治疗机制的研究目标。尽管 LTL 与妊娠史无显著差异，但纵向分析可能有助于确定与前瞻性捕获的妊娠作用的相互作用。
