Abstract Details

Title Accelerated Metabolomic Age and Its Association with Social Determinants of Health in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:00 PM-6:00 PM)

Poster/Presentation
Number 1-005

Objective To assess differences in metabolomic age between people with multiple sclerosis (PwMS) and healthy controls (HC), and investigate the association between accelerated metabolomic aging and social determinants of health (SDoH).

Background Biological age, a more accurate indicator of health than chronological age, is influenced by lifestyle and environmental exposures. SDoH have been linked to accelerated biological aging in diseases other than MS. Metabolomics captures changes in internal and environmental factors, enabling the estimation of biological age and its relationship to SDoH.

Design/Methods Metabolomic age was calculated for 541 samples from PwMS (73.93% on disease-modifying therapy (DMT), 72.08% female) and 142 samples from HC (74.64% female) across a total of 389 individuals. An external dataset of 174 samples, consisting of 102 HC (72.55% female) and 72 MS (all DMT-naïve, 77.78% female), was also analyzed. Metabolomic age was calculated using an aging model derived from the metabolomic profiles of 11,977 healthy individuals, measured using the same untargeted platform utilized for both datasets. Accelerated aging was defined as the difference between metabolomic and chronological age. SDoH were characterized using the Area Deprivation Index (ADI) in the first cohort. Between-group comparisons were performed using t-tests, and linear regression assessed the association between metabolomic age and ADI.

Results PwMS on average, had 10.11 years (95% CI: 7.1, 13.17) greater age acceleration (metabolomic – chronological age) compared to HC (p<0.0001). This finding was validated in the external dataset (MS vs HC; p=0.037). Increasing social deprivation was associated with faster biological aging. A 5-percentile increase in ADI was associated with a 0.34-year (95% CI: 0.07, 0.61) increase in age acceleration in PwMS (p=0.02).

Conclusions PwMS exhibit significantly accelerated metabolomic aging compared to HC. The association between biological aging and SDoH suggests that biological aging may be a key mechanism linking SDoH to disease outcomes in MS.

Authors/Disclosures
Fatemeh Siavoshi, MD PRESENTER	Dr. Siavoshi has nothing to disclose.
Rezvan Rose Noroozi, PhD	Dr. Noroozi has nothing to disclose.
Farren Briggs, PhD (University of Miami Miller School of Medicine)	The institution of Prof. Briggs has received research support from NIH.
Pavan Bhargava, MD, FAAN (Johns Hopkins University)	The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.
Kathryn Fitzgerald, PhD (Johns Hopkins University)	Dr. Fitzgerald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Setpoint Medical. The institution of Dr. Fitzgerald has received research support from NIH. The institution of Dr. Fitzgerald has received research support from National MS Society.

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