多发性硬化症中加速的代谢组学衰老及其与健康社会决定因素的关联
Accelerated Metabolomic Aging and Its Association with Social Determinants of Health in Multiple Sclerosis.
作者信息
Siavoshi Fatemeh, Noroozi Rezvan, Chang Gina, Schoeps Vinicius A, Smith Matthew D, Briggs Farren B S, Graves Jennifer S, Waubant Emmanuelle, Mowry Ellen M, Calabresi Peter A, Bhargava Pavan, Fitzgerald Kathryn C
机构信息
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
出版信息
medRxiv. 2025 May 5:2025.01.29.25321260. doi: 10.1101/2025.01.29.25321260.
OBJECTIVES
Biological age may better capture differences in disease course among people with multiple sclerosis (PwMS) of identical chronological age. We investigated biological age acceleration through metabolomic age (mAge) in PwMS and its association with social determinants of health (SDoH) measured by area deprivation index (ADI).
METHODS
mAge was calculated for three cohorts: 323 PwMS and 66 healthy controls (HCs); 101 HCs and 71 DMT-naïve PwMS; and 64 HCs and 67 pediatric-onset MS/clinically isolated syndrome patients, using an aging clock derived from 11,977 healthy adults. mAge acceleration, the difference between mAge and chronological age, was compared between groups using generalized linear and mixed-effects models, and its association with ADI was assessed via linear regression.
RESULTS
Cross-sectionally, PwMS had higher age acceleration than HCs: 9.77 years in adult PwMS (95% CI:6.57-12.97, p=5.3e-09), 4.90 years in adult DMT-naïve PwMS (95% CI:0.85-9.01, p=0.02), and 6.98 years (95% CI:1.58-12.39, p=0.01) in pediatric-onset PwMS. Longitudinally, PwMS aged 1.19 mAge years per chronological year (95% CI:0.18, 2.20; p=0.02), faster than HCs. In PwMS, a 10-percentile increase in ADI was associated with a 0.63-year (95% CI:0.10-1.18; p=0.02) increase in age acceleration.
DISCUSSION
We demonstrated accelerated mAge in adult and pediatric-onset PwMS and its association with social disadvantage.
目的
生物年龄可能更能体现相同实际年龄的多发性硬化症患者（PwMS）在疾病进程上的差异。我们通过代谢组年龄（mAge）研究了PwMS的生物年龄加速情况及其与通过区域剥夺指数（ADI）衡量的健康社会决定因素（SDoH）之间的关联。
方法
使用源自11977名健康成年人的衰老时钟，为三个队列计算mAge：323名PwMS患者和66名健康对照（HCs）；101名HCs和71名未使用疾病修正治疗（DMT）的PwMS患者；以及64名HCs和67名儿童期发病的多发性硬化症/临床孤立综合征患者。使用广义线性和混合效应模型比较组间的mAge加速情况（即mAge与实际年龄之间的差异），并通过线性回归评估其与ADI的关联。
结果
横断面研究中，PwMS的年龄加速高于HCs：成年PwMS患者为9.77岁（95%置信区间：6.57 - 12.97，p = 5.3×10⁻⁹），成年未使用DMT的PwMS患者为4.90岁（95%置信区间：0.85 - 9.01，p = 0.02），儿童期发病的PwMS患者为6.98岁（95%置信区间：1.58 - 12.39，p = 0.01）。纵向研究中，PwMS患者每实际年龄年的mAge增长为1.19岁（95%置信区间：0.18，2.20；p = 0.02），比HCs更快。在PwMS患者中，ADI每增加10个百分点，年龄加速增加0.63岁（95%置信区间：0.10 - 1.18；p = 0.02）。
讨论
我们证明了成年和儿童期发病的PwMS患者存在mAge加速，且其与社会劣势相关。
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