Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：与衰老相关的过程有助于多发性硬化症（MS）的神经变性和残疾。生物老化的生物标志物，如白细胞端粒长度（LTL）可以帮助个性化预后。妊娠已被证明对MS女性的残疾积累具有保护作用，尽管目前尚不清楚这种作用是否与衰老机制或LTL有关。
目的：本研究旨在对MS患者队列中的LTL进行横断面表征，并将LTL与残疾严重程度和妊娠史相关联。
方法：我们从墨尔本501名MS患者的全血中提取DNA，澳大利亚。扩展的残疾状况量表（EDSS）得分和人口统计数据，以及197名女性的怀孕史，是在样品收集时获得的。从MSBaseRegistry中提取了其他数据。使用实时定量聚合酶链反应以碱基对（bp）确定LTL。
结果：EDSS评分和较短的LTL之间的关系对于人口统计学和临床因素（包括实际年龄）的多变量调整是稳健的，EDSS每增加1.0个调整后的LTL减少97.1bp(95%CI=9.7-184.5bp，p=0.030)。调整后的中介分析发现，实际年龄占LTL和EDSS评分之间关系的33.6％（p=0.018）。在有怀孕数据的女性中，妊娠史与年龄相关（中位数49.7岁vs33.0岁，p<0.001)。调整后的LTL与任何妊娠史之间没有显着关系（LTL增加65.3bp，95%CI=-471.0-601.5bp，p=0.81）或完成妊娠的数量（每次妊娠LTL增加14.6bp，95%CI=-170.3-199.6个基点，p=0.87）。
结论：LTL与残疾之间的相关性与实际年龄和其他因素无关，这表明MS的神经储备与生物衰老之间存在联系，以及病理生理和治疗机制的潜在研究目标。虽然LTL与妊娠史没有显著差异，纵向分析有助于确定与前瞻性妊娠效应的相互作用.
目的：本研究旨在对MS患者队列中的LTL进行横断面表征，并将LTL与残疾严重程度和妊娠史相关联。
方法：我们从墨尔本501名MS患者的全血中提取DNA，澳大利亚。扩展的残疾状况量表（EDSS）得分和人口统计数据，以及197名女性的怀孕史，是在样品收集时获得的。从MSBaseRegistry中提取了其他数据。使用实时定量聚合酶链反应以碱基对（bp）确定LTL。
结果：EDSS评分和较短的LTL之间的关系对于人口统计学和临床因素（包括实际年龄）的多变量调整是稳健的，EDSS每增加1.0个调整后的LTL减少97.1bp(95%CI=9.7-184.5bp，p=0.030)。调整后的中介分析发现，实际年龄占LTL和EDSS评分之间关系的33.6％（p=0.018）。在有怀孕数据的女性中，妊娠史与年龄相关（中位数49.7岁vs33.0岁，p<0.001)。调整后的LTL与任何妊娠史之间没有显着关系（LTL增加65.3bp，95%CI=-471.0-601.5bp，p=0.81）或完成妊娠的数量（每次妊娠LTL增加14.6bp，95%CI=-170.3-199.6个基点，p=0.87）。
结论：LTL与残疾之间的相关性与实际年龄和其他因素无关，这表明MS的神经储备与生物衰老之间存在联系，以及病理生理和治疗机制的潜在研究目标。虽然LTL与妊娠史没有显著差异，纵向分析有助于确定与前瞻性妊娠效应的相互作用.
