Rejuvenation of Regeneration in the Aging Central Nervous System
Open accessAbstract
Remyelination is a regenerative process in the central nervous system (CNS) that produces new myelin sheaths from adult stem cells. The decline in remyelination that occurs with advancing age poses a significant barrier to therapy in the CNS, particularly for long-term demyelinating diseases such as multiple sclerosis (MS). Here we show that remyelination of experimentally induced demyelination is enhanced in old mice exposed to a youthful systemic milieu through heterochronic parabiosis. Restored remyelination in old animals involves recruitment to the repairing lesions of blood-derived monocytes from the young parabiotic partner, and preventing this recruitment partially inhibits rejuvenation of remyelination. These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life.
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Older patients are likely to remain receptive to regenerative therapies.
“Thus, older patients are likely to remain receptive to regenerative therapies, which is in line with the conclusions drawn from experimental mouse models (41).”
From BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions (2017) · cites this paper as [41]
The Discussion concludes that aged oligodendrocyte progenitor cells remain responsive to signals that promote repair and identifies them as potential targets for remyelination therapy, including in MS patients. The claim extends that conclusion from a specific CNS repair process to older patients’ receptiveness to regenerative therapies generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMicroglia/macrophages exhibit regenerative properties through the phagocytosis of myelin debris and secretion of growth/neurotrophic factors.
“they also exhibit regenerative properties through the phagocytosis of myelin debris3, 4 and secretion of growth/neurotrophic factors5.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [4]
Pairing of an old animal with a young animal (Y/O) led to increased densities of M2 microglia/macrophages in the lesions in the older animal relative to O/O pairings.
“Pairing of an old animal with a young animal (Y/O), a manipulation that restores remyelination efficiency in the older animal4, led to increased densities of M2 microglia/macrophages in the lesions in the older animal relative to those seen in the O/O pairings (Fig. 6b, c).”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [4]
Macrophages remove myelin debris to promote myelin regeneration and reverse age-related dedifferentiation of oligodendrocytes.
“macrophages remove myelin debris to promote myelin regeneration and reverse the age-related dedifferentiation of oligodendrocytes,433”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [433]
Blood-borne factors also influence stem cell changes in the aging central nervous system.
“This surgical intervention also enhances rates of neurogenesis, remyelination and other measures of neural function in the old parabiont, suggesting that changes in stem cell function in the aging central nervous system are also affected by blood-borne factors165–167.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [167]
The same surgery raises neurogenesis, remyelination and other neural function measures in the older parabiont.
“This surgical intervention also enhances rates of neurogenesis, remyelination and other measures of neural function in the old parabiont, suggesting that changes in stem cell function in the aging central nervous system are also affected by blood-borne factors165–167.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [167]
Factors in the blood are able to communicate information from one or more source tissues to other tissues throughout the body.
“These findings, as well as many follow up studies,66,67,68 including the demonstration that plasma infusions alone are sufficient to exert these effects,65,69 have unequivocally demonstrated that factors in the blood are able to communicate information from one or more source tissues to other tissues throughout the body.”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [66]
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- Authors
- Ruckh, J. M., Zhao, J.-W., Shadrach, J. L., van Wijngaarden, P., Rao, T. N., Wagers, A. J., & Franklin, R. J. M.
- Affiliations
- University of Cambridge (GB)
- Joslin Diabetes Center (US)
- Corresponding author
- Wagers, Amy J.
- Franklin, Robin J.M.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 10
- Issue
- 1
- Pages
- 96-103
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3714794
- OpenAlex
- W2111256919
- Cited by
- 649
- References
- 30
- Citations by year
- 2026: 25 · 2025: 29 · 2024: 45 · 2023: 43 · 2022: 48 · 2021: 49 · 2020: 57 · 2019: 60 · 2018: 47 · 2017: 45 · 2016: 45 · 2015: 50 · 2014: 44 · 2013: 36 · 2012: 24
- FWCI
- 35.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (079249)
- Rosetrees Trust
- National Institutes of Health (1dp2od004345-01)
- Harvard Stem Cell Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- remyelination, aging, central nervous system regeneration, heterochronic parabiosis, monocyte recruitment, demyelinating disease, multiple sclerosis, adult stem cells, rejuvenation
- MeSH terms
- Aging, Animals, Central Nervous System, Monocytes, Multiple Sclerosis, Myelin Sheath, Regeneration, Mice, Knockout, Mice, Adult Stem Cells
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