# Markers of Biological Aging in Multiple Sclerosis

> **NIH NIH R03** · OHIO STATE UNIVERSITY · 2022 · $157,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the central nervous system
affecting nearly one million people in the United States. Age is the predominant driver of disease progression
in MS, and older individuals with MS are at higher risk of conversion to secondary-progressive MS (SPMS),
which is a disease phenotype marked by progressive worsening of neurological function over time and
resistance to MS disease-modifying therapies. The onset of SPMS can be delayed or prevented through early
aggressive treatment of MS; nevertheless, this strategy involves using higher risk therapies, so it is important
to identify those who will derive the most benefit from this treatment strategy. Current understanding of aging in
MS is mostly limited to epidemiological studies of chronological age in patients with MS. Increasing evidence
on the biological mechanisms of aging shows variations among individuals that are often inaccurately reflected
by their chronological age. These mechanisms involve genetic pathways and biochemical processes that
regulate the accumulation of damage over time, which eventually overwhelm compensatory repair
mechanisms and lead to age-related decline. Measuring biological age in MS would uncover mechanisms by
which age affects disease course and identify patients at risk of conversion to SPMS. Nevertheless,
differences in biological age among people with MS have not been adequately characterized, and the effects of
biological aging on disease course remain unknown. This proposed study will be the first to measure multiple
distinct hallmarks of biological aging using established aging biomarkers including leukocyte telomere length
reflecting telomere attrition, p16INK4a as a marker of cellular senescence, and the epigenetic clock as a
measure of age-associated DNA methylation patterns. For aim 1, we will measure the aforementioned serum
aging biomarkers in patients with MS and age- and sex-matched healthy controls. For aim 2, we will determine
associations between biomarkers of aging and their associations with MS disease characteristics in a cross-
sectional study and with exploratory longitudinal observations for one year. This research will determine the
differential contributions of various aging mechanism to MS disease outcomes and represents a critical step to
identifying patients at risk of worse disease outcomes who may benefit from early high-intensity therapies to
prevent or delay the onset of SPMS. This award will support the applicant’s development as a clinician scientist
by integrating principles of geroscience with neurology. The successful completion of the aims will lay the
foundation for a future career development award application and lead to opportunities for incorporating
measurements of biological aging to identify individuals with RRMS at higher risk for conversion to SPMS who
may benefit from early aggressive treatment.

## Key facts

- **NIH application ID:** 10518840
- **Project number:** 1R03AG078946-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Yinan Zhang
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $157,500
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518840

## Citation

> US National Institutes of Health, RePORTER application 10518840, Markers of Biological Aging in Multiple Sclerosis (1R03AG078946-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10518840. Licensed CC0.

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