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Updated: Aug 9, 2026
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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Temporal changes in metabolism guide oligodendrocyte precursor cell dynamics in aging and multiple sclerosis
Tess Dierckx1, Sarah E Wilson2, Rebecca Buchanan1
1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Neuron
|August 7, 2026
Summary
Aging disrupts oligodendrocyte precursor cell (OPC) function by affecting circadian clock gene Bmal1, impacting myelin repair. Targeting BMAL1-controlled pathways may restore OPC dynamics in aging and multiple sclerosis.
Area of Science:
- Neuroscience
- Cell Biology
- Chronobiology
Background:
- Oligodendrocyte precursor cell (OPC) differentiation is crucial for myelin repair but declines with age and in multiple sclerosis (MS).
- The impact of aging on OPC deficits and the underlying molecular mechanisms, particularly those involving circadian rhythms, are not fully understood.
Purpose of the Study:
- To investigate how aging affects OPCs and their differentiation capacity.
- To explore the role of the circadian clock gene Bmal1 in OPC function, metabolism, and senescence.
- To assess the therapeutic potential of targeting BMAL1-controlled pathways for myelin repair.
Main Methods:
- Comparative analysis of aged versus young OPCs for gene expression and metabolic function.
- Genetic manipulation of Bmal1 in OPCs to study its effects on cellular dynamics and senescence.
- Assessment of OPC proliferation and differentiation rates over a 24-hour cycle in young and aged mice.
- Investigating the efficacy of chronotherapeutic targeting of BMAL1-Sirtuin signaling in demyelination models.
- Analysis of iPSC-derived OPCs from MS patients and MS lesion oligodendroglia.
Main Results:
- Aged OPCs exhibit dysregulation of circadian clock genes, including Bmal1, and altered metabolism compared to young OPCs.
- Loss of Bmal1 in OPCs leads to metabolic dysfunction, cellular senescence, and impaired cellular dynamics.
- Circadian disruption in OPC proliferation and differentiation is observed with aging.
- Targeting BMAL1-controlled sirtuin signaling, specifically Sirt2, can restore OPC dynamics after demyelination.
- MS patient-derived OPCs and lesion oligodendroglia show similar BMAL1 and SIRT2 disruptions.
Conclusions:
- BMAL1 is a critical regulator of OPC energy metabolism, sirtuin homeostasis, and senescence.
- Circadian clock dysregulation contributes to impaired myelin renewal in aging and MS.
- BMAL1-Sirtuin pathways represent a potential therapeutic target for enhancing myelin repair in aging-related neurological disorders and MS.
