Accelerated Metabolomic Aging and Its Association with Social Determinants of Health in Multiple Sclerosis.

Fatemeh Siavoshi, Rezvan Noroozi, Gina Chang, Vinicius A Schoeps, Matthew D Smith, Farren B S Briggs, Jennifer S Graves, Emmanuelle Waubant, Ellen M Mowry, Peter A Calabresi, Pavan Bhargava, Kathryn C Fitzgerald
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Abstract

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.

多发性硬化症患者代谢组学加速老化及其与健康社会决定因素的关系
生物年龄(BA)由遗传、生活方式和环境影响决定,它反映了生理变化,并在多发性硬化症(MS)以外的疾病中介导健康的社会决定因素(SDoH)的影响。我们通过对多发性硬化症患者(PwMS)的代谢谱分析,研究了 BA 加速及其与 SDoH(以地区贫困指数衡量)之间的关系。在独立的成人和儿童多发性硬化症队列中,与健康对照组相比,我们观察到多发性硬化症患者的 BA 加速。社会贫困程度越高,PwMS 的 BA 加速程度越高。这些发现凸显了 BA 是连接 SDoH 与 MS 结果的潜在中介,也是减少健康差异的目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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