# Associations of biological aging with outcomes and immune dysregulation in multiple sclerosis

> **NIH NIH K23** · OHIO STATE UNIVERSITY · 2024 · $161,671

## Abstract

PROJECT SUMMARY/ABSTRACT
Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the central nervous system
afflicting around one million people in the United States. The disease often presents with a relapsing-remitting
phase followed by gradual conversion to secondary progressive MS (SPMS) characterized by irreversible
accrual of disability and unresponsiveness to current disease-modifying therapies for MS. Age carries the
highest risk for developing SPMS, yet the underlying cellular, molecular, and genetic processes contributing to
biological aging are understudied in MS. Recent progress in aging research have led to the emergence of
geroscience as an interdisciplinary approach that seeks to reduce the incidence and severity of chronic age-
related diseases by understanding aging physiology and developing clinical interventions targeting aging
mechanisms. However, no studies to date have investigated the role of biological aging in MS using
established markers of cellular senescence (p16INK4a) and epigenetic aging (age-associated DNA methylation
patterns, or epigenetic clocks). The Trans-NIH Geroscience Interest Group recently emphasized a need to
engage researchers and clinicians across multidisciplinary specialties to translate geroscience discoveries into
effective clinical practices. Through the completion of this career development award, Dr. Zhang will become
one of few clinician scientists in the country whose research combines principles of geroscience with
neurology. This proposed study will investigate the associations of biological aging with clinical outcomes (aim
1), neuroimaging findings (aim 2), and immune dysregulation (aim 3) in people with MS. The study will consist
of a cross-sectional analysis of baseline associations of biological aging with MS outcomes and a 2-year
longitudinal analysis of the rate of biological aging with changes in MS outcomes. Dr. Zhang has assembled a
multidisciplinary mentorship team to achieve his career development goals of establishing a geroscience
framework to study MS by integrating clinical, neuroimaging, and molecular mechanistic studies. The
successful completion of this project will enable future studies to 1) use biological aging as a prognostic
biomarker in MS to employ early aggressive treatment in individuals with accelerated biological aging and 2)
conduct trials of anti-aging therapies in combination with MS disease-modifying therapies to mitigate or even
prevent MS progression.

## Key facts

- **NIH application ID:** 10785765
- **Project number:** 1K23AG084848-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Yinan Zhang
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,671
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785765

## Citation

> US National Institutes of Health, RePORTER application 10785765, Associations of biological aging with outcomes and immune dysregulation in multiple sclerosis (1K23AG084848-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10785765. Licensed CC0.

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