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Updated: Jun 8, 2026
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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Distinct age-related pattern of mitochondrial somatic mutations across multiple sclerosis phenotypes
Federica Esposito1,2, Kaalindi Misra1, Francesca Doyle1
1Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Journal of Neurology
|June 6, 2026
Summary
Somatic mitochondrial DNA (mtDNA) mutations increase with age in multiple sclerosis (MS) patients, particularly in primary progressive MS. This age-related mutation burden differs significantly based on MS disease course.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Mitochondrial dysfunction is implicated in neurodegeneration in multiple sclerosis (MS).
- The role of age-accumulated somatic mitochondrial DNA (mtDNA) mutations in MS progression is understudied.
- Investigating mtDNA mutation burden in relation to age and MS disease course is crucial.
Purpose of the Study:
- To examine the association between age and somatic mtDNA mutation burden in MS patients.
- To determine if this association varies across different MS disease courses.
Main Methods:
- Sequenced whole mtDNA from blood-derived DNA of 404 MS patients.
- Defined somatic mutations based on heteroplasmy levels (1-5%).
- Employed linear regression models to analyze age and mutation rate associations.
Main Results:
- A significant age-dependent increase in low-frequency non-synonymous mtDNA mutations was observed in MS.
- This age effect was primarily driven by patients with primary progressive MS (PPMS).
- Fast-progressing MS patients showed a positive age-mutation rate correlation, while slow-progressing patients exhibited an inverse trend.
Conclusions:
- Evidence supports differential age-related accumulation of somatic mtDNA mutations in blood across MS disease courses.
- Findings highlight distinct mitochondrial aging trajectories in different MS subtypes.
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