The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Open accessAbstract
Excess signaling is bad for the aging brain: Preventing antiviral-like responses may protect function in the aging brain. Baruch et al. monitored messenger RNA production in the choroid plexus, the interface between the blood and cerebrospinal fluid, in young and old mice (see the Perspective by Ransohoff). They detected an inflammatory response in older mice not present in the brain of young mice that was also seen in old aged human samples postmortem. Preventing signaling by the cytokine interferon-I, which normally helps in the antiviral response of the immune system, helped prevent the decrease in cognitive function seen in aged mice. Science , this issue p. 89 ; see also p. 36
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
“Astrocytes and microglia, mediators of the innate immune response of the central nervous system, become hyper-activated with age (Baruch et al., 2014; Norden and Godbout, 2013).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Baruch et al., 2014
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
“Overall, we observed an upregulation of the inflammatory signals in the aged ChP in agreement with prior studies (Baruch et al., 2014) that was reflected in expression of Ifit1 and Il1b in aged epithelial cells.”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Baruch et al., 2014
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
“Recent findings from parabiosis models (left) have shown that exposure to young blood restores neurogenesis, learning and memory and neuronal functions in older mice via increase in growth factors and endothelial remodeling in older mice(Baruch et al, 2014;Katsimpardi et al, 2014;Villeda et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Baruch et al, 2014
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
“In addition, it has been found that the level of IFN-γ was reduced at the CP of aging brain,148 indicating an attenuated ability to resolve inflammation in aging brain.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [148]
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
“The presence of a type I IFN signature in brain cells, in particular in microglia, is increasingly being associated with ageing and neurodegenerative disease in various species13,15,39,44–50.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [15]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Cells harboring PSMC5 variants exhibit characteristics reminiscent of senescent or neurodegenerative cells, including impaired mitophagy47, type I IFN response48, abnormal apolipoproteins and/or cholesterol levels49,50, cognitive inflexibility51,52, impaired neuritogenesis53,54, and an imbalanced E/I ratio55,56.”
From Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies (2025) · cites this paper as [48]
The cited source says what the claim attributes to it.
In the citing paper
“Recent findings from parabiosis models (left) have shown that exposure to young blood restores neurogenesis, learning and memory and neuronal functions in older mice via increase in growth factors and endothelial remodeling in older mice(Baruch et al, 2014;Katsimpardi et al, 2014;Villeda et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Baruch et al, 2014
In the citing paper
“The inflamed choroid plexus has previously been shown to send inflammatory signals into the brain, thereby activating parenchymal glia and impairing cognitive function31.”
From Dysregulation of brain and choroid plexus cell types in severe COVID-19 (2021) · cites this paper as [31]
In the citing paper
“so it is plausible that Cluster OA3 microglia also play a role in contributing to the inflammatory tone of the aged brain.”
From Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain (2018) · cites this paper as Baruch et al., 2014
In the citing paper
“Although IFNγ can also have positive effects, IFNα has an overall negative impact on the brain137. Chronic inflammation and IFNα convert αNSCs into ΩNSCs, which are more quiescent138.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [137]
In the citing paper
“These were enriched for specialized programs across ages: Embryonic epithelia upregulated genes for developmental processes (Figure 3K, S3K), while aged epithelia upregulated host-defense programs (Figure 3L, FDR q-value < 0.01, GOrilla (Eden et al., 2007, 2009;Baruch et al., 2014).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Baruch et al., 2014
In the citing paper
“IL-1β expression was induced in aged ChP macrophages”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Baruch et al., 2014
In the citing paper
“Moreover, neutralizing antibodies against IFN-I restored growth factor levels and cognitive functioning in aged mice, thus demonstrating the role of blood-derived factors in aging-induced neurological deficits (Baruch et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Baruch et al, 2014
In the citing paper
“Indeed, gene expression analysis of the choroid plexus, a brain region marked by epithelial lining that serves as a neurovascular interface, revealed an aging-induced upregulation of interferon-I (IFN-I) and downregulation of interferon-II response genes (Baruch et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Baruch et al, 2014
In the citing paper
“Recent findings from parabiosis models (left) have shown that exposure to young blood restores neurogenesis, learning and memory and neuronal functions in older mice via increase in growth factors and endothelial remodeling in older mice(Baruch et al, 2014;Katsimpardi et al, 2014;Villeda et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Baruch et al, 2014
In the citing paper
“Recent findings from parabiosis models (left) have shown that exposure to young blood restores neurogenesis, learning and memory and neuronal functions in older mice via increase in growth factors and endothelial remodeling in older mice(Baruch et al, 2014;Katsimpardi et al, 2014;Villeda et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Baruch et al, 2014
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
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Functional neurogenesis in the adult hippocampus
van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., & Gage, F. H. (2002) · Nature · doi:10.1038/4151030a · Cited by 2,853
Inflammatory Blockade Restores Adult Hippocampal Neurogenesis
Monje, M. L., Toda, H., & Palmer, T. D. (2003) · Science · doi:10.1126/science.1088417 · Cited by 2,426
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
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?
Deng, W., Aimone, J. B., & Gage, F. H. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2822 · Cited by 2,120
Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types
Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., Elefant, N., Paul, F., Zaretsky, I., Mildner, A., Cohen, N., Jung, S., Tanay, A., et al. (2014) · Science · doi:10.1126/science.1247651 · Cited by 1,795
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
Self-citationInflammation is detrimental for neurogenesis in adult brain
Ekdahl, C. T., Claasen, J.-H., Bonde, S., Kokaia, Z., & Lindvall, O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234031100 · Cited by 1,559
Guttman, M., Garber, M., Levin, J. Z., Donaghey, J., Robinson, J., Adiconis, X., Fan, L., Koziol, M. J., Gnirke, A., Nusbaum, C., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1633 · Cited by 1,253
Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J., & Schwartz, M. (2006) · Nature Neuroscience · doi:10.1038/nn1629 · Cited by 1,209
Self-citationDistinct Effects of T-bet in T H 1 Lineage Commitment and IFN-γ Production in CD4 and CD8 T Cells
Szabo, S. J., Sullivan, B. M., Stemmann, C., Satoskar, A. R., Sleckman, B. P., & Glimcher, L. H. (2002) · Science · doi:10.1126/science.1065543 · Cited by 1,172
Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice
Villeda, S. A., Plambeck, K. E., Middeldorp, J., Castellano, J. M., Mosher, K. I., Luo, J., Smith, L. K., Bieri, G., Lin, K., Berdnik, D., et al. (2014) · Nature Medicine · doi:10.1038/nm.3569 · Cited by 1,081
Self-citationVascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors
Katsimpardi, L., Litterman, N. K., Schein, P. A., Miller, C. M., Loffredo, F. S., Wojtkiewicz, G. R., Chen, J. W., Lee, R. T., Wagers, A. J., & Rubin, L. L. (2014) · Science · doi:10.1126/science.1251141 · Cited by 1,037
Immunomodulatory functions of type I interferons
González-Navajas, J. M., Lee, J., David, M., & Raz, E. (2012) · Nature reviews. Immunology · doi:10.1038/nri3133 · Cited by 1,030
The anatomical and cellular basis of immune surveillance in the central nervous system
Ransohoff, R. M., & Engelhardt, B. (2012) · Nature reviews. Immunology · doi:10.1038/nri3265 · Cited by 1,029
Ageing and neuronal vulnerability
Mattson, M. P., & Magnus, T. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1886 · Cited by 957
Persistent LCMV infection is controlled by blockade of type I interferon signaling
Teijaro, J. R., Ng, C., Lee, A. M., Sullivan, B. M., Sheehan, K. C. F., Welch, M., Schreiber, R. D., Carlos de la Torre, J., & Oldstone, M. B. A. (2013) · Science · doi:10.1126/science.1235214 · Cited by 755
Blockade of chronic type I interferon signaling to control persistent LCMV infection
Wilson, E. B., Yamada, D. H., Elsaesser, H., Herskovitz, J., Deng, J., Cheng, G., Aronow, B. J., Karp, C. L., & Brooks, D. G. (2013) · Science · doi:10.1126/science.1235208 · Cited by 709
Shechter, R., Miller, O., Yovel, G., Rosenzweig, N., London, A., Ruckh, J., Kim, K.-W., Klein, E., Kalchenko, V., Bendel, P., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.012 · Cited by 683
Self-citationBurgess, A., Vigneron, S., Brioudes, E., Labbé, J., Lorca, T., & Castro, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914191107 · Cited by 681
Immune activation in brain aging and neurodegeneration: too much or too little?
Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679
Self-citationKipnis, J., Cohen, H., Cardon, M., Ziv, Y., & Schwartz, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402268101 · Cited by 510
Self-citationPrinz, M., Schmidt, H., Mildner, A., Knobeloch, K., Hanisch, U., Raasch, J., Merkler, D., Detje, C. N., Gutcher, I., Mages, J., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.011 · Cited by 387
Type I Interferon Suppresses Type II Interferon–Triggered Human Anti-Mycobacterial Responses
Teles, R. M. B., Graeber, T. G., Krutzik, S. R., Montoya, D. J., Schenk, M., Lee, D. J., Komisopoulou, E., Kelly‐Scumpia, K. M., Chun, R. F., Iyer, S. S., et al. (2013) · Science · doi:10.1126/science.1233665 · Cited by 375
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349
Self-citationWolf, S. A., Steiner, B., Akpinarli, A., Kammertoens, T., Nassenstein, C., Braun, A., Blankenstein, T., & Kempermann, G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0801218 · Cited by 329
The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans
Wichers, M., & Maes, M. (2002) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145702003103 · Cited by 329
IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair
Kunis, G., Baruch, K., Rosenzweig, N., Kertser, A., Miller, O., Berkutzki, T., & Schwartz, M. (2013) · Brain · doi:10.1093/brain/awt259 · Cited by 321
Self-citationBaruch, K., Ron‐Harel, N., Gal, H., Deczkowska, A., Shifrut, E., Ndifon, W. O., Mirlas-Neisberg, N., Cardon, M., Vaknin, I., Cahalon, L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211270110 · Cited by 303
Self-citationRescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities
Oliveira, A. M. M., Hemstedt, T. J., & Bading, H. (2012) · Nature Neuroscience · doi:10.1038/nn.3151 · Cited by 289
Alamed, J., Wilcock, D. M., Diamond, D. M., Gordon, M. N., & Morgan, D. (2006) · Nature Protocols · doi:10.1038/nprot.2006.275 · Cited by 256
The Blood–Cerebrospinal Fluid Barrier: Structure and Functional Significance
Johanson, C. E., Stopa, E. G., & McMillan, P. N. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-938-3_4 · Cited by 249
Pro-cognitive properties of T cells
Kipnis, J., Gadani, S., & Derecki, N. C. (2012) · Nature Reviews Immunology · doi:10.1038/nri3280 · Cited by 246
The choroid plexus in the rise, fall and repair of the brain
Emerich, D. F., Skinner, S. J. M., Borlongan, C. V., Vasconcellos, A. V., & Thanos, C. G. (2005) · BioEssays · doi:10.1002/bies.20193 · Cited by 202
CNS-specific T cells shape brain function via the choroid plexus
Baruch, K., & Schwartz, M. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.04.002 · Cited by 200
Self-citationRecruiting adaptive cellular stress responses for successful brain ageing
Stranahan, A. M., & Mattson, M. P. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3151 · Cited by 170
The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain
Johanson, C. E., Stopa, E. G., McMillan, P. N., Roth, D. R., Funk, J., & Krinke, G. J. (2010) · Toxicologic Pathology · doi:10.1177/0192623310394214 · Cited by 112
Insights into CNS ageing from animal models of senescence
Yeoman, M. S., Scutt, G., & Faragher, R. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3230 · Cited by 98
The path from the choroid plexus to the subventricular zone: go with the flow!
Falcão, A. M. (2012) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2012.00034 · Cited by 98
Age-dependent spatial memory loss can be partially restored by immune activation
Ron-Harel, N., Segev, Y., Lewitus, G. M., Cardon, M., Ziv, Y., Netanely, D., Jacob-Hirsch, J., Amariglio, N., Rechavi, G., Domany, E., et al. (2008) · Rejuvenation Research · doi:10.1089/rej.2008.0755 · Cited by 73
Self-citationImmune senescence and brain aging: can rejuvenation of immunity reverse memory loss?
Ron‐Harel, N., & Schwartz, M. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.03.003 · Cited by 60
Self-citationType I interferon in neurological disease—The devil from within
Hofer, M. J., & Campbell, I. L. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.03.006 · Cited by 50
Type 1 Interferons Cool the Inflamed Brain
Axtell, R. C., & Steinman, L. (2008) · Immunity · doi:10.1016/j.immuni.2008.04.006 · Cited by 39
Cited by
Sorted by citations
Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., Segel, M., Nemesh, J., Saunders, A., et al. (2018) · doi:10.1101/406140 · Cited by 2,225
Immunopathology of multiple sclerosis
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3871 · Cited by 2,215
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668
Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4106 · Cited by 1,559
Microglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180
Self-citation
Metadata
- Authors
- Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., Amit, I., & Schwartz, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Stanford Medicine (US)
- Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Corresponding author
- Baruch, Kuti
- Deczkowska, Aleksandra
- Amit, Ido
- Schwartz, Michal
- ORCID
- Venue
- Science
- Published
- 2014-10-03
- Volume
- 346
- Issue
- 6205
- Pages
- 89-93
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4869326
- OpenAlex
- W2061769617
- Cited by
- 615
- References
- 44
- Citations by year
- 2026: 52 · 2025: 47 · 2024: 58 · 2023: 64 · 2022: 69 · 2021: 60 · 2020: 60 · 2019: 56 · 2018: 32 · 2017: 28 · 2016: 47 · 2015: 37 · 2014: 5
- FWCI
- 20.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Medical Research Council (MR/L022656/1)
- National Institute on Aging (AG045034, R01AG045034)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- aging, type I interferon, choroid plexus, cognitive decline, cerebrospinal fluid, hippocampal neurogenesis, antiviral response, brain aging, aged mice
- MeSH terms
- Interferon gamma Receptor, Aging, Animals, Brain, Choroid Plexus, Cognition, Gene Expression Regulation, Hippocampus, Interferon Type I, Mice, Transgenic, Receptors, Interferon, Interferon Regulatory Factors, Mice, Neurogenesis
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
