Oct 5, 2019

Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells

Cell Stem Cell
Björn NeumannRobin J M Franklin

Abstract

The age-related failure to produce oligodendrocytes from oligodendrocyte progenitor cells (OPCs) is associated with irreversible neurodegeneration in multiple sclerosis (MS). Consequently, regenerative approaches have significant potential for treating chronic demyelinating diseases. Here, we show that the differentiation potential of adult rodent OPCs decreases with age. Aged OPCs become unresponsive to pro-differentiation signals, suggesting intrinsic constraints on therapeutic approaches aimed at enhancing OPC differentiation. This decline in functional capacity is associated with hallmarks of cellular aging, including decreased metabolic function and increased DNA damage. Fasting or treatment with metformin can reverse these changes and restore the regenerative capacity of aged OPCs, improving remyelination in aged animals following focal demyelination. Aged OPCs treated with metformin regain responsiveness to pro-differentiation signals, suggesting synergistic effects of rejuvenation and pro-differentiation therapies. These findings provide insight into aging-associated remyelination failure and suggest therapeutic interventions for reversing such declines in chronic disease.

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Mentioned in this Paper

Metformin
Cell Aging
Remyelination
Rejuvenation
Chronic Disease
Nerve Degeneration
Differential Diagnosis
Cell Differentiation Process
Oligodendroglia
Demyelination

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