Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors
Open accessAbstract
Help the Aged: Muscle function declines with age, as does neurogenesis in certain brain regions. Two teams analyzed the effects of heterochronic parabiosis in mice. Sinha et al. (p. 649 ) found that when an aged mouse shares a circulatory system with a youthful mouse, the aged mouse sees improved muscle function, and Katsimpardi et al. (p. 630 ) observed increased generation of olfactory neurons. In both cases, Growth Differentiation Factor 11 appeared to be one of the key components of the young blood.
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
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?
Preclinical studies have demonstrated that GDF11 in young plasma exerts neuroprotective effects by promoting neurogenesis within the hippocampus and enhancing learning and memory in aged mice.
“Preclinical studies have demonstrated that growth differentiation factor-11 (GDF11) in young plasma exerts neuroprotective effects by promoting neurogenesis within the hippocampus and enhancing learning and memory in aged mice.72”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [72]
The levels of antiageing factors such as GDF11, TIMP2 and CSF2 are reduced; these factors are linked to improved microglial phagocytosis and neurogenesis and reduce the amyloid-β load, thus enhancing cognition.
“In contrast, the levels of antiageing factors, such as GDF11, tissue inhibitor of metalloproteinase 2 (TIMP2) and granulocyte‒macrophage colony stimulating factor (CSF2), are reduced. These factors are linked to improved microglial phagocytosis and neurogenesis and reduce the Aβ load, thus enhancing cognition.72,322–324”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [72]
In old mice, extra GDF11 reverses cardiac hypertrophy, improves neural stem cell and neuronal function, and increases physical activity.
“GDF11 supplementation in old mice further reverses age-related hypertrophy in cardiac muscle168, enhances neural stem cell and neuronal function166 and improves physical activity38.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [166]
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 [166]
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 [166]
Part of the rejuvenation from a young systemic environment seems tied to higher circulating GDF11 and oxytocin in young versus old blood.
“Intriguingly, at least part of the ‘rejuvenating’ effect of a young systemic environment appears related to the higher levels of circulating growth differentiation factor 11 (GDF11) and oxytocin present in young blood as compared to aged38,166,168,169.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [166]
Heterochronic parabiosis with young blood in old mice increased neurogenesis and dendritic spine density and improved age-related cognitive impairment.
“Recent heterochronic parabiosis experiments demonstrated that introduction of young blood in old mice led to increased neurogenesis and dendritic spine density, and improved age-related cognitive impairment, (Katsimpardi et al., 2014; Villeda et al., 2014).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Katsimpardi et al., 2014
Studies on heterochronic parabiosis and plasma exchange in animals have demonstrated that circulating proteins can have a causal influence on ageing phenotypes across the body, including in skeletal muscle, heart and brain.
“Studies on heterochronic parabiosis and plasma exchange in animals have demonstrated that circulating proteins can have a causal influence on ageing phenotypes across the body, including in skeletal muscle107,108, heart109 and brain15,110–112.”
From Measuring biological age using omics data (2022) · cites this paper as [111]
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 [68]
Another study using parabiosis showed brain endothelium remodeling and restoration of cerebral blood flow in aged mice exposed to young blood.
“Corresponding with these findings, another study using parabiosis showed brain endothelium remodeling and restoration of cerebral blood flow in aged mice exposed to young blood (Katsimpardi et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Katsimpardi et al, 2014
The study attributed the aging-associated vascular and blood flow impairments specifically to reduced circulating levels of GDF11.
“The study attributed the aging-associated vascular and blood flow impairments specifically to reduced circulating levels of GDF11, a secreted protein of the TGF family (Katsimpardi et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Katsimpardi et al, 2014
Exposure to young blood restores neuronal functions in older mice.
“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 Katsimpardi et al, 2014
The restoration by young blood in older mice is via increase in growth factors and endothelial remodeling.
“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 Katsimpardi et al, 2014
Exposure to young blood restores neurogenesis in older mice.
“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 Katsimpardi et al, 2014
Exposure to young blood restores learning and memory in older mice.
“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 Katsimpardi 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.
Cites
Reynolds, B. A., & Weiss, S. (1992) · Science · doi:10.1126/science.1553558 · Cited by 5,413 · see citing works
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880 · see citing works
The Neuroendocrinology of Stress: A Never Ending Story
Lightman, S. L. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01711.x · Cited by 3,570 · see citing works
Kuhn, H., Dickinson-Anson, H., & Gage, F. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-06-02027.1996 · Cited by 3,139 · see citing works
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 1,788 · see citing works
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 · see citing works
Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells
Shen, Q., Goderie, S. K., Jin, L., Karanth, N., Sun, Y., Abramova, N. E., Vincent, P. A., Pumiglia, K. M., & Temple, S. (2004) · Science · doi:10.1126/science.1095505 · Cited by 1,538 · see citing works
Adult hippocampal neurogenesis buffers stress responses and depressive behaviour
Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011) · Nature · doi:10.1038/nature10287 · Cited by 1,473 · see citing works
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 · see citing works
Self-citationÁlvarez-Buylla, A., & Lim, D. A. (2004) · Neuron · doi:10.1016/s0896-6273(04)00111-4 · Cited by 1,320 · see citing works
Cerebral microvascular pathology in aging and Alzheimer's disease
Farkas, E., & Luiten, P. G. M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00068-x · Cited by 1,102 · see citing works
A specialized vascular niche for adult neural stem cells
Tavazoie, M., Van der Veken, L., Silva-Vargas, V., Louissaint, M., Colonna, L., Zaidi, B., Garcia-Verdugo, J. M., & Doetsch, F. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.025 · Cited by 1,033 · see citing works
Kim, S. (1995) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910340303 · Cited by 1,001 · see citing works
Loffredo, F. S., Steinhauser, M. L., Jay, S. M., Gannon, J., Pancoast, J. R., Yalamanchi, P., Sinha, M., Dall’Osso, C., Khong, D., Shadrach, J. L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.015 · Cited by 948 · see citing works
Self-citationPhysiological 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 · see citing works
Self-citationRestoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle
Sinha, M., Jang, Y. C., Oh, J., Khong, D., Wu, E. Y., Manohar, R., Miller, C., Regalado, S. G., Loffredo, F. S., Pancoast, J. R., et al. (2014) · Science · doi:10.1126/science.1251152 · Cited by 824 · see citing works
Self-citationBecoming a new neuron in the adult olfactory bulb
Carleton, A., Petreanu, L., Lansford, R. D., Álvarez-Buylla, A., & Lledo, P. (2003) · Nature Neuroscience · doi:10.1038/nn1048 · Cited by 808 · see citing works
Age-Dependent Impairment of Angiogenesis
Rivard, A., Fabre, J., Silver, M., Chen, D., Murohara, T., Kearney, M., Magner, M., Asahara, T., & Isner, J. M. (1999) · Circulation · doi:10.1161/01.cir.99.1.111 · Cited by 774 · see citing works
Pregnancy-Stimulated Neurogenesis in the Adult Female Forebrain Mediated by Prolactin
Shingo, T., Gregg, C., Enwere, E. K., Fujikawa, H., Hassam, R., Geary, C. L., Cross, J. C., & Weiss, S. (2003) · Science · doi:10.1126/science.1076647 · Cited by 711 · see citing works
Rejuvenation of Regeneration in the Aging Central Nervous System
Ruckh, J. M., Zhao, J.-W., Shadrach, J. L., van Wijngaarden, P., Rao, T. N., Wagers, A. J., & Franklin, R. J. M. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2011.11.019 · Cited by 649 · see citing works
Self-citationEmerging biological roles for erythropoietin in the nervous system
Brines, M., & Cerami, A. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1687 · Cited by 523 · see citing works
Blood vessels and nerves: common signals, pathways and diseases
Carmeliet, P. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1158 · Cited by 513 · see citing works
Tropepe, V., Craig, C. G., Morshead, C. M., & van der Kooy, D. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-20-07850.1997 · Cited by 442 · see citing works
Age-related production of new granule cells in the adult dentate gyrus
Seki, T., & Arai, Y. (1995) · Neuroreport · doi:10.1097/00001756-199512150-00010 · Cited by 386 · see citing works
Role of the CNS microvascular pericyte in the blood-brain barrier
Balabanov, R. D., & Dore‐Duffy, P. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980915)53:6 · Cited by 304 · see citing works
The aging neurogenic subventricular zone
Luo, J., Daniels, S. B., Lennington, J. B., Notti, R. Q., & Conover, J. C. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00197.x · Cited by 285 · see citing works
Age-Related Changes in Regional Cerebral Blood Flow during Working Memory for Faces
Grady, C. L., McIntosh, A. R., Bookstein, F. L., Horwitz, B., Rapoport, S. I., & Haxby, J. V. (1998) · NeuroImage · doi:10.1006/nimg.1998.0376 · Cited by 240 · see citing works
Microvascular plasticity in aging
Riddle, D. R., Sonntag, W. E., & Lichtenwalner, R. J. (2003) · Ageing Research Reviews · doi:10.1016/s1568-1637(02)00064-8 · Cited by 222 · see citing works
Garcia, A. D. R., Steiner, B., Kronenberg, G., Bick‐Sander, A., & Kempermann, G. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00130.x · Cited by 209 · see citing works
Seki, T. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10387 · Cited by 202 · see citing works
In Vivo Imaging of Cerebral Microvascular Plasticity from Birth to Death
Harb, R., Whiteus, C., Freitas, C., & Grutzendler, J. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.152 · Cited by 182 · see citing works
Wu, P., Shen, Q., Dong, S., Xu, Z., Tsien, J. Z., & Hu, Y. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.03.028 · Cited by 116 · see citing works
Impaired Angiogenesis in the Aged
Reed, M. J., & Edelberg, J. M. (2004) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2004.7.pe7 · Cited by 100 · see citing works
Olfactory Behavioral Testing in the Adult Mouse
Witt, R. M., Galligan, M. M., Despinoy, J. R., & Segal, R. A. (2009) · Journal of Visualized Experiments · doi:10.3791/949 · Cited by 73 · see citing works
Katsimpardi, L., Gaitanou, M., Malnou, C. E., Lledo, P., Charneau, P., Matsas, R., & Thomaidou, D. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0921 · Cited by 51 · see citing works
Self-citationRole of nitric oxide in subventricular zone neurogenesis
Matarredona, E. R., Murillo‐Carretero, M., Moreno‐López, B., & Estrada, C. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.01.001 · Cited by 50 · see citing works
Olfactory Behavioral Testing in the Adult Mouse
Witt, R. M., Galligan, M. M., Despinoy, J. R., et al. (2009) · Journal of Visualized Experiments · doi:10.3791/949-v · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Daneman, R., & Prat, A. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020412 · Cited by 3,437 · see citing works
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Human Hippocampal Neurogenesis Persists throughout Aging
Boldrini, M., Fulmore, C. A., Tartt, A. N., Simeon, L. R., Pavlova, I., Poposka, V., Rosoklija, G. B., Stankov, A., Arango, V., Dwork, A. J., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.03.015 · Cited by 1,345 · see citing works
Ageing, neurodegeneration and brain rejuvenation
Wyss-Coray, T. (2016) · Nature · doi:10.1038/nature20411 · Cited by 1,147 · see citing works
Undulating changes in human plasma proteome profiles across the lifespan
Lehallier, B., Gate, D., Schaum, N., Nanasi, T., Lee, S. E., Yousef, H., Moran Losada, P., Berdnik, D., Keller, A., Verghese, J., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0673-2 · Cited by 981 · see citing works
Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., Dubeau, L., Yap, L. P., Park, R., Vinciguerra, M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.012 · Cited by 850 · see citing works
Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle
Sinha, M., Jang, Y. C., Oh, J., Khong, D., Wu, E. Y., Manohar, R., Miller, C., Regalado, S. G., Loffredo, F. S., Pancoast, J. R., et al. (2014) · Science · doi:10.1126/science.1251152 · Cited by 824 · see citing works
Self-citationA systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain
Wang, J., Gu, B. J., Masters, C. L., & Wang, Y.-J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.111 · Cited by 808 · see citing works
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796 · see citing works
Self-citationAdult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later
Bond, A. M., Ming, G.-L., & Song, H. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.003 · Cited by 791 · see citing works
Single-cell transcriptomic profiling of the aging mouse brain
Ximerakis, M., Lipnick, S. L., Innes, B. T., Simmons, S. K., Adiconis, X., Dionne, D., Mayweather, B. A., Nguyen, L., Niziolek, Z., Ozek, C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0491-3 · Cited by 736 · see citing works
Self-citationRunning-induced systemic cathepsin B secretion is associated with memory function
Moon, H. Y., Becke, A., Berron, D., Becker, B., Sah, N., Benoni, G., Janke, E., Lubejko, S. T., Greig, N. H., Mattison, J. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.025 · Cited by 628 · see citing works
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615 · see citing works
Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain
Obernier, K., & Alvarez-Buylla, A. (2019) · Development · doi:10.1242/dev.156059 · Cited by 578 · see citing works
Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K., & Tremblay, M. (2017) · The Journal of Physiology · doi:10.1113/jp272134 · Cited by 562 · see citing works
Measuring biological age using omics data
Rutledge, J., Oh, H., & Wyss-Coray, T. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00511-7 · Cited by 570 · see citing works
Horowitz, A. M., Fan, X., Bieri, G., Smith, L. K., Sanchez-Diaz, C. I., Schroer, A. B., Gontier, G., Casaletto, K. B., Kramer, J. H., Williams, K. E., et al. (2020) · Science · doi:10.1126/science.aaw2622 · Cited by 496 · see citing works
β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis
Smith, L. K., He, Y., Park, J.-S., Bieri, G., Snethlage, C. E., Lin, K., Gontier, G., Wabl, R., Plambeck, K. E., Udeochu, J., et al. (2015) · Nature Medicine · doi:10.1038/nm.3898 · Cited by 500 · see citing works
Renal Aging: Causes and Consequences
O’Sullivan, E. D., Hughes, J., & Ferenbach, D. A. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015121308 · Cited by 484 · see citing works
Neurogenesis in the embryonic and adult brain: same regulators, different roles
Urbán, N., & Guillemot, F. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00396 · Cited by 493 · see citing works
The quest to slow ageing through drug discovery
Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0067-7 · Cited by 468 · see citing works
Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442 · see citing works
Yousef, H., Czupalla, C. J., Lee, D., Chen, M. B., Burke, A. N., Zera, K. A., Zandstra, J., Berber, E., Lehallier, B., Mathur, V., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0440-4 · Cited by 442 · see citing works
Human umbilical cord plasma proteins revitalize hippocampal function in aged mice
Castellano, J. M., Mosher, K. I., Abbey, R. J., McBride, A. A., James, M. L., Berdnik, D., Shen, J. C., Zou, B., Xie, X. S., Tingle, M., et al. (2017) · Nature · doi:10.1038/nature22067 · Cited by 445 · see citing works
Aging of hematopoietic stem cells
de Haan, G., & Lazare, S. S. (2018) · Blood · doi:10.1182/blood-2017-06-746412 · Cited by 432 · see citing works
Ageing and rejuvenation of tissue stem cells and their niches
Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407 · see citing works
Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain
Kalamakis, G., Brüne, D., Ravichandran, S., Bolz, J., Fan, W., Ziebell, F., Stiehl, T., Catalá-Martinez, F., Kupke, J., Zhao, S., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.040 · Cited by 399 · see citing works
Microglia Priming with Aging and Stress
Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398 · see citing works
Oligodendrocyte Progenitor Cells Become Regionally Diverse and Heterogeneous with Age
Spitzer, S. O., Sitnikov, S., Kamen, Y., Evans, K. A., Kronenberg-Versteeg, D., Dietmann, S., de Faria, O., Agathou, S., & Káradóttir, R. T. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.020 · Cited by 364 · see citing works
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336 · see citing works
Beckervordersandforth, R., Ebert, B., Schäffner, I., Moss, J., Fiebig, C., Shin, J., Moore, D. L., Ghosh, L., Trinchero, M. F., Stockburger, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.017 · Cited by 303 · see citing works
Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells
Silva-Vargas, V., Maldonado-Soto, A. R., Mizrak, D., Codega, P., & Doetsch, F. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.06.013 · Cited by 306 · see citing works
Platelet factors attenuate inflammation and rescue cognition in ageing
Schroer, A. B., Ventura, P. B., Sucharov, J., Misra, R., Chui, M. K. K., Bieri, G., Horowitz, A. M., Smith, L. K., Encabo, K., Tenggara, I., et al. (2023) · Nature · doi:10.1038/s41586-023-06436-3 · Cited by 252 · see citing works
Aging and Rejuvenation of Neural Stem Cells and Their Niches
Navarro Negredo, P., Yeo, R. W., & Brunet, A. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.07.002 · Cited by 246 · see citing works
Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues
Chen, M. B., Yang, A. C., Yousef, H., Lee, D., Chen, W., Schaum, N., Lehallier, B., Quake, S. R., & Wyss-Coray, T. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.012 · Cited by 233 · see citing works
“Standing out in this list are Bmpr2 (ligands: BMP7 and GDF9), Ifnar1 (ligand: IFNA10), Igf1r (ligands: CDH1, GPC3, and INS), all of which have been implicated in organismal longevity and brain aging and whose plasma ligands similarly change with age (Katsimpardi et al., 2014; Kimura et al., 1997; Loffredo et al., 2013…”
Molecular mechanisms of renal aging
Schmitt, R., & Melk, A. (2017) · Kidney International · doi:10.1016/j.kint.2017.02.036 · Cited by 235 · see citing works
Changes in Regenerative Capacity through Lifespan
Yun, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025392 · Cited by 216 · see citing works
Peripheral immune system in aging and Alzheimer’s disease
Cao, W., & Zheng, H. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0284-2 · Cited by 214 · see citing works
A mosaic world: puzzles revealed by adult neural stem cell heterogeneity
Chaker, Z., Codega, P., & Doetsch, F. (2016) · WIREs Developmental Biology · doi:10.1002/wdev.248 · Cited by 198 · see citing works
The aging skin microenvironment dictates stem cell behavior
Ge, Y., Miao, Y., Gur-Cohen, S., Gomez, N., Yang, H., Nikolova, M., Polak, L., Hu, Y., Verma, A., Elemento, O., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901720117 · Cited by 190 · see citing works
Gontier, G., Iyer, M., Shea, J. M., Bieri, G., Wheatley, E. G., Ramalho-Santos, M., & Villeda, S. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.001 · Cited by 197 · see citing works
Xu, R., Brawner, A. T., Li, S., Liu, J.-J., Kim, H., Xue, H., Pang, Z. P., Kim, W.-Y., Hart, R. P., Liu, Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.014 · Cited by 193 · see citing works
Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration
Pluvinage, J. V., & Wyss-Coray, T. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0255-9 · Cited by 191 · see citing works
Translational strategies and challenges in regenerative medicine
Dimmeler, S., Ding, S., Rando, T. A., & Trounson, A. (2014) · Nature Medicine · doi:10.1038/nm.3627 · Cited by 179 · see citing works
Lei, Q., Gao, F., Liu, T., Ren, W., Chen, L., Cao, Y., Chen, W., Guo, S., Zhang, Q., Chen, W., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz8697 · Cited by 170 · see citing works
Crane, J. D., MacNeil, L. G., Lally, J. S., Ford, R. J., Bujak, A. L., Brar, I. K., Kemp, B. E., Raha, S., Steinberg, G. R., & Tarnopolsky, M. A. (2015) · Aging Cell · doi:10.1111/acel.12341 · Cited by 179 · see citing works
Preclinical Assessment of Young Blood Plasma for Alzheimer Disease
Middeldorp, J., Lehallier, B., Villeda, S. A., Miedema, S. S. M., Evans, E., Czirr, E., Zhang, H., Luo, J., Stan, T., Mosher, K. I., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.3185 · Cited by 153 · see citing works
Blood-to-brain communication in aging and rejuvenation
Bieri, G., Schroer, A. B., & Villeda, S. A. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01238-8 · Cited by 156 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
Molecular hallmarks of heterochronic parabiosis at single-cell resolution
Pálovics, R., Keller, A., Schaum, N., Tan, W., Fehlmann, T., Borja, M., Kern, F., Bonanno, L., Calcuttawala, K., Webber, J., et al. (2022) · Nature · doi:10.1038/s41586-022-04461-2 · Cited by 153 · see citing works
Cosacak, M. I., Bhattarai, P., Reinhardt, S., Petzold, A., Dahl, A., Zhang, Y., & Kizil, C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.090 · Cited by 116 · see citing works
Systemic Nutrient and Stress Signaling via Myokines and Myometabolites
Rai, M., & Demontis, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105305 · Cited by 123 · see citing works
Asynchronous, contagious and digital aging
Rando, T. A., & Wyss-Coray, T. (2021) · Nature Aging · doi:10.1038/s43587-020-00015-1 · Cited by 121 · see citing works
Gan, K. J., & Südhof, T. C. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902672116 · Cited by 114 · see citing works
The road ahead for health and lifespan interventions
Gonzalez-Freire, M., Diaz-Ruiz, A., Hauser, D., Martinez-Romero, J., Ferrucci, L., Bernier, M., & de Cabo, R. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101037 · Cited by 118 · see citing works
Sha, S. J., Deutsch, G. K., Tian, L., Richardson, K., Coburn, M., Gaudioso, J. L., Marcal, T., Solomon, E., Boumis, A., Bet, A., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.3288 · Cited by 109 · see citing works
Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain
Wheatley, E. G., Albarran, E., White, C. W., Bieri, G., Sanchez-Diaz, C., Pratt, K., Snethlage, C. E., Ding, J. B., & Villeda, S. A. (2019) · Current Biology · doi:10.1016/j.cub.2019.08.003 · Cited by 107 · see citing works
Young bone marrow transplantation preserves learning and memory in old mice
Das, M. M., Godoy, M., Chen, S., Moser, V. A., Avalos, P., Roxas, K. M., Dang, I., Yáñez, A., Zhang, W., Bresee, C., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0298-5 · Cited by 98 · see citing works
Aged hematopoietic stem cells are refractory to bloodborne systemic rejuvenation interventions
Ho, T. T., Dellorusso, P. V., Verovskaya, E. V., Bakker, S. T., Flach, J., Smith, L. K., Ventura, P. B., Lansinger, O. M., Hérault, A., Zhang, S. Y., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20210223 · Cited by 101 · see citing works
Translating the Science of Aging into Therapeutic Interventions
Kirkland, J. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025908 · Cited by 78 · see citing works
Blood-Borne Revitalization of the Aged Brain
Castellano, J. M., Kirby, E. D., & Wyss-Coray, T. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.1616 · Cited by 83 · see citing works
Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity
bin Imtiaz, M. K., Jaeger, B. N., Bottes, S., Machado, R. A. C., Vidmar, M., Moore, D. L., & Jessberger, S. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.01.015 · Cited by 83 · see citing works
Can exercise training teach us how to treat Alzheimer's disease?
Huuha, A. M., Norevik, C. S., Moreira, J. B. N., Kobro-Flatmoen, A., Scrimgeour, N., Kivipelto, M., Van Praag, H., Ziaei, M., Sando, S. B., Wisløff, U., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101559 · Cited by 79 · see citing works
Harper (2016) · doi:10.1161/circresaha.116.307962 · Cited by 74 · see citing works
Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues
Yousefzadeh, M. J., Wilkinson, J. E., Hughes, B., Gadela, N., Ladiges, W. C., Vo, N., Niedernhofer, L. J., Huffman, D. M., & Robbins, P. D. (2020) · GeroScience · doi:10.1007/s11357-020-00185-1 · Cited by 70 · see citing works
Xia, W., Li, M., Jiang, X., Huang, X., Gu, S., Ye, J., Zhu, L., Hou, M., & Zan, T. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01348-2 · Cited by 72 · see citing works
Lindbohm, J. V., Mars, N., Walker, K. A., Singh‐Manoux, A., Livingston, G., Brunner, E. J., Sipilä, P. N., Saksela, K., Ferrie, J. E., Lovering, R. C., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12419 · Cited by 70 · see citing works
Whittemore, K., Derevyanko, A., Martinez, P., Serrano, R., Pumarola, M., Bosch, F., & Blasco, M. A. (2019) · Aging · doi:10.18632/aging.101982 · Cited by 69 · see citing works
Untangling senescent and damage‐associated microglia in the aging and diseased brain
Ng, P. Y., McNeely, T. L., & Baker, D. J. (2023) · The FEBS Journal · doi:10.1111/febs.16315 · Cited by 68 · see citing works
Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59 · see citing works
Matters of context guide future research in TGFβ superfamily signaling
Akhurst, R. J., & Padgett, R. W. (2015) · Science Signaling · doi:10.1126/scisignal.aad0416 · Cited by 52 · see citing works
Bast, L., Calzolari, F., Strasser, M. K., Hasenauer, J., Theis, F. J., Ninkovic, J., & Marr, C. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.088 · Cited by 50 · see citing works
Klotho, the Key to Healthy Brain Aging?
Vo, H. T., Laszczyk, A. M., & King, G. D. (2017) · Brain Plasticity · doi:10.3233/bpl-170057 · Cited by 50 · see citing works
Katsimpardi, L., Kuperwasser, N., Camus, C., Moigneu, C., Chiche, A., Tolle, V., Li, H., Kokovay, E., & Lledo, P. (2020) · Aging Cell · doi:10.1111/acel.13038 · Cited by 47 · see citing works
Self-citationMyostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs
Rodgers, B. D., & Ward, C. W. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab030 · Cited by 111 · see citing works
Hornsby, A. K. E., Buntwal, L., Carisi, M. C., Santos, V. V., Johnston, F., Roberts, L. D., Sassi, M., Mequinion, M., Stark, R., Reichenbach, A., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100120 · Cited by 35 · see citing works
Mitsumori, R., Sakaguchi, K., Shigemizu, D., Mori, T., Akiyama, S., Ozaki, K., Niida, S., & Shimoda, N. (2020) · PLOS ONE · doi:10.1371/journal.pone.0239196 · Cited by 34 · see citing works
Modeling motor neuron disease: the matter of time
Arbab, M., Baars, S., & Geijsen, N. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.008 · Cited by 33 · see citing works
The aged hematopoietic system promotes hippocampal‐dependent cognitive decline
Smith, L. K., Verovskaya, E., Bieri, G., Horowitz, A. M., von Ungern‐Sternberg, S. N. I., Lin, K., Seizer, P., Passegué, E., & Villeda, S. A. (2020) · Aging Cell · doi:10.1111/acel.13192 · Cited by 31 · see citing works
Xia, E., Xu, F., Hu, C., Kumal, J. P. P., Tang, X., Mao, D., Li, Y., Wu, D., Zhang, R., Wu, S., et al. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.08.010 · Cited by 22 · see citing works
Kang, S., Moser, V. A., Svendsen, C. N., & Goodridge, H. S. (2020) · Communications Biology · doi:10.1038/s42003-020-0797-4 · Cited by 22 · see citing works
The protein inputs of an ultra-predictive aging clock represent viable anti-aging drug targets
Johnson, A. A., Shokhirev, M. N., & Lehallier, B. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101404 · Cited by 22 · see citing works
Tashiro, R., Ozaki, D., Bautista-Garrido, J., Sun, G., Obertas, L., Mobley, A. S., Kim, G. S., Aronowski, J., & Jung, J. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065187 · Cited by 15 · see citing works
Vascular Senescence: A Potential Bridge Between Physiological Aging and Neurogenic Decline
Rojas-Vázquez, S., Blasco-Chamarro, L., López-Fabuel, I., Martínez-Máñez, R., & Fariñas, I. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666881 · Cited by 15 · see citing works
Zhang, K., Liu, P., Yuan, L., Geng, Z., Li, B., & Zhang, B. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.07.058 · Cited by 12 · see citing works
Activated GDF11/8 subforms predict cardiovascular events and mortality in humans
Walker, R. G., Kato, T., Ben Driss, L., Williams, S. A., Hinterberg, M. A., Janjic, N., Gelinas, A. D., Carpenter, M. A., Kattamuri, C., Walter, J. E., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61815-w · Cited by 4 · see citing works
Self-citation
- Authors
- 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.
- Affiliations
- Harvard University (US)
- Joslin Diabetes Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Katsimpardi, Lida
- Rubin, Lee L.
- ORCID
- Venue
- Science
- Published
- 2014-05-09
- Volume
- 344
- Issue
- 6184
- Pages
- 630-634
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4123747
- OpenAlex
- W2067028731
- Cited by
- 1,037
- References
- 37
- Citations by year
- 2026: 46 · 2025: 74 · 2024: 64 · 2023: 84 · 2022: 88 · 2021: 93 · 2020: 102 · 2019: 94 · 2018: 91 · 2017: 86 · 2016: 86 · 2015: 82 · 2014: 45
- FWCI
- 34.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1dp2od004345-01)
- National Institute on Aging (R01AG033053, R01AG032977, R01AG040019)
- National Heart, Lung, and Blood Institute (U01HL100402)
- National Institute of Neurological Disorders and Stroke (R01NS072167, R01NS070835)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- brain aging, neurogenesis, neurogenic niche, vascular remodeling, GDF11, neural stem cells, cerebral blood flow, odor discrimination, cognitive function, neurovascular disease
- MeSH terms
- Aging, Animals, Brain, Cerebrovascular Circulation, Cognition, Endothelium, Vascular, Male, Mice, Inbred C57BL, Olfactory Bulb, Parabiosis, Recombinant Proteins, Rejuvenation, Bone Morphogenetic Proteins, Mice, Growth Differentiation Factors, Neurogenesis, Neural 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
