Healthy Aging News and ResearchMetformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells.

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AlbertY
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Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells.

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In this landmark study, the Robin Franklin group has addressed possible reasons for this failure to remyelinate. In contrast to the bulk of studies within the field that utilize OPCs isolated from young rodents, this study optimized protocols to isolate OPCs from either young adults (2-3 months) or aged rats (20-24 months), and the authors compared their differentiation rates into mature myelin basic protein-expressing oligodendrocytes. The aged OPCs differentiated at a much slower rate, thus suggesting intrinsic changes with aging. RNA-Seq of the two populations identified the upregulation of the genes typical of senescence in the aged cells, as well as increased DNA damage. Dietary restriction has been known to enhance the function of aged adult stem cells in a variety of regenerative processes.

They thus tested whether alternate day fasting (ADF) for 6 months would enhance the remyelination capacity of endogenous OPCs in aged rats versus younger rats. They utilized the well-tested model of cerebellar demyelination induced by ethidium bromide injections and examined remyelination 50 days post-lesion. The extent of remyelination was massively enhanced in animals subjected to ADF, and the proportion of mature oligodendrocytes also increased. Isolation of the OPCs from the different animal groups confirmed that the cells from aged ADF rats indeed differentiated faster into MBP+ oligodendrocytes, similarly to the OPCs from young rats.

They subsequently tested whether the known and clinically accepted drug metformin (which modulates relevant nutrient signaling pathways and is used to treat type 2 diabetes) was able to replicate the effects of fasting on cultured aged OPCs. This was indeed the case. Strikingly, metformin treatment of rats in vivo also yielded results, thus showing the remyelination of demyelinated lesions comparable to ADF. Metformin thus appears to reverse age-related changes in the OPCs.

https://doi.org/10.1016/j.stem.2019.08.015


Ph.D. student at Harvard Medical School, doing research on aging