The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The many roles of chemokines and chemokine receptors in inflammation
Charo, I. F., & Ransohoff, R. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra052723 · Cited by 2,523
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005) · Nature · doi:10.1038/nature03260 · Cited by 2,287
Self-citationThe ageing systemic milieu negatively regulates neurogenesis and cognitive function
Villeda, S. A., Luo, J., Mosher, K. I., Zou, B., Britschgi, M., Bieri, G., Stan, T. M., Fainberg, N., Ding, Z., Eggel, A., et al. (2011) · Nature · doi:10.1038/nature10357 · Cited by 1,763
Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
Brack, A. S., Conboy, M. J., Roy, S., Lee, M., Kuo, C. J., Keller, C., & Rando, T. A. (2007) · Science · doi:10.1126/science.1144090 · Cited by 1,564
Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells
Wagers, A. J., Sherwood, R. I., Christensen, J. L., & Weissman, I. L. (2002) · Science · doi:10.1126/science.1074807 · Cited by 1,460
Self-citationBoring, L., Gosling, J., Chensue, S. W., Kunkel, S. L., Farese, R. V., Broxmeyer, H. E., & Charo, I. F. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119798 · Cited by 1,096
Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M., & Rossi, F. M. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2887 · Cited by 1,061
Physiological Migration of Hematopoietic Stem and Progenitor Cells
Wright, D. E., Wagers, A. J., Gulati, A. P., Johnson, F. L., & Weissman, I. L. (2001) · Science · doi:10.1126/science.1064081 · Cited by 933
Self-citationKuhlmann, T., Miron, V., Cuo, Q., Wegner, C., Antel, J., & Bruck, W. (2008) · Brain · doi:10.1093/brain/awn096 · Cited by 864
Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
Jaskelioff, M., Muller, F. L., Paik, J.-H., Thomas, E., Jiang, S., Adams, A. C., Sahin, E., Kost-Alimova, M., Protopopov, A., Cadiñanos, J., et al. (2011) · Nature · doi:10.1038/nature09603 · Cited by 857 · cited 1×
“Recent data suggest that age-associated defects in neural stem cells can be reversed by reactivation of telomerase (Jaskelioff et al., 2011), suggesting that aged OPCs might, in principle, remain competent for efficient remyelination.”
BackgroundShechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000113 · Cited by 770
Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation
Kotter, M. R., Li, W.-W., Zhao, C., & Franklin, R. J. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2615-05.2006 · Cited by 768
Self-citationDefects in Macrophage Recruitment and Host Defense in Mice Lacking the CCR2 Chemokine Receptor
Kurihara, T., Warr, G. A., Loy, J. K., & Bravo, R. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.10.1757 · Cited by 732
Sim, F. J., Zhao, C., Penderis, J., & Franklin, R. J. M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02451.2002 · Cited by 625
Self-citationAge at disability milestones in multiple sclerosis
Confavreux, C., & Vukusic, S. (2006) · Brain · doi:10.1093/brain/awh714 · Cited by 544
Shen, S., Sandoval, J., Swiss, V. A., Li, J., Dupree, J. L., Franklin, R. J. M., & Casaccia‐Bonnefil, P. (2008) · Nature Neuroscience · doi:10.1038/nn.2172 · Cited by 499
Self-citationbHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS
Arnett, H. A., Fancy, S. P. J., Alberta, J. A., Zhao, C., Plant, S. R., Kaing, S., Raine, C. S., Rowitch, D. H., Franklin, R. J. M., & Stiles, C. D. (2004) · Science · doi:10.1126/science.1103709 · Cited by 416
Self-citationRemyelination capacity of the MS brain decreases with disease chronicity
Goldschmidt, T., Antel, J., König, F. B., Brück, W., & Kuhlmann, T. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a8260a · Cited by 411
Woodruff, R. H., Fruttiger, M., Richardson, W. D., & Franklin, R. J. M. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2003.10.014 · Cited by 335
Self-citationCentral remyelination restores secure conduction
Smith, K. J., Blakemore, W. F., & MCDONALD, W. I. (1979) · Nature · doi:10.1038/280395a0 · Cited by 332
Promotion of wound repair in old mice by local injection of macrophages.
Danon, D., Kowatch, M. A., & Roth, G. S. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.6.2018 · Cited by 252
Arai, K., & Lo, E. H. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0035-09.2009 · Cited by 246
Extensive remyelination of the CNS leads to functional recovery
Duncan, I. D., Brower, A., Kondo, Y., Curlee, J. F., & Schultz, R. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812500106 · Cited by 227
Baer, A. S., Syed, Y. A., Kang, S. U., Mitteregger, D., Vig, R., ffrench-Constant, C., Franklin, R. J. M., Altmann, F., Lubec, G., & Kotter, M. R. (2009) · Brain · doi:10.1093/brain/awn334 · Cited by 211
Self-citationMason, J. L., Xuan, S., Dragatsis, I., Efstratiadis, A., & Goldman, J. E. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07710.2003 · Cited by 177
Delayed Changes in Growth Factor Gene Expression during Slow Remyelination in the CNS of Aged Rats
Hinks, G. L., & Franklin, R. J. M. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0897 · Cited by 156
Self-citationThe distribution of transferrin immunoreactivity in the rat central nervous system
Connor, J. R., & Fine, R. E. (1986) · Brain Research · doi:10.1016/0006-8993(86)90576-7 · Cited by 149
Long-Term Culture of Purified Postnatal Oligodendrocyte Precursor Cells
Tang, D. G., Tokumoto, Y. M., & RAFF, M. C. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.148.5.971 · Cited by 145
Platelet-Derived Growth Factor Promotes Repair of Chronically Demyelinated White Matter
Vana, A. C., Flint, N. C., Harwood, N. E., Le, T. Q., Fruttiger, M., & Armstrong, R. C. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181587d46 · Cited by 101
The role of CNS glia in preserving axon function
Edgar, J. M., & Nave, K. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.08.003 · Cited by 91
Cited by
Sorted by citations
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595
Reich, D. S., Lucchinetti, C. F., & Calabresi, P. A. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1401483 · Cited by 2,491
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,777
Self-citationAgeing, neurodegeneration and brain rejuvenation
Wyss-Coray, T. (2016) · Nature · doi:10.1038/nature20411 · Cited by 1,147
Metadata
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review