Systemic Regulation of the Age-Related Decline of Pancreatic β-Cell Replication
Open accessAbstract
The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic factor found in the circulation of young mice is able to increase the proliferation rate of old pancreatic β-cells. Old mice parabiosed to young mice have increased β-cell replication compared with unjoined old mice or old mice parabiosed to old mice. In addition, we demonstrate that old β-cells transplanted into young recipients have increased replication rate compared with cells transplanted into old recipients; conversely, young β-cells transplanted into old mice decrease their replication rate compared with young cells transplanted into young recipients. The expression of p16/INK4A mRNA did not change in heterochronic parabiosis, suggesting the involvement of other pathways. We conclude that systemic factors contribute to the replicative decline of old pancreatic β-cells.
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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 [67]
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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 · see citing works
The 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
The signals and pathways activating cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.10.013 · Cited by 1,046 · see citing works
p16INK4a induces an age-dependent decline in islet regenerative potential
Krishnamurthy, J., Ramsey, M. R., Ligon, K. L., Torrice, C., Koh, A., Bonner-Weir, S., & Sharpless, N. E. (2006) · Nature · doi:10.1038/nature05092 · Cited by 1,003 · cited 1× · see citing works
“The p16 deficiency reduces and p16 overexpression enhances the age-related decline in b-cell replication (9).”
BackgroundImbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells
Carlson, M. E., Hsu, M., & Conboy, I. M. (2008) · Nature · doi:10.1038/nature07034 · Cited by 483 · see citing works
Very Slow Turnover of β-Cells in Aged Adult Mice
Teta, M., Long, S. Y., Wartschow, L. M., Rankin, M. M., & Kushner, J. A. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2557 · Cited by 465 · see citing works
Apoptosis Participates in the Remodeling of the Endocrine Pancreas in the Neonatal Rat
Scaglia, L., Cahill, C. J., Finegood, D. T., & Bonner‐Weir, S. (1997) · Endocrinology · doi:10.1210/endo.138.4.5069 · Cited by 418 · see citing works
Chen, H., Gu, X., Su, I.-H., Bottino, R., Contreras, J. L., Tarakhovsky, A., & Kim, S. K. (2009) · Genes & Development · doi:10.1101/gad.1742509 · Cited by 366 · see citing works
Islet growth and development in the adult
Bonner‐Weir, S. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0240297 · Cited by 332 · see citing works
Adaptive β-Cell Proliferation Is Severely Restricted With Advanced Age
Rankin, M. M., & Kushner, J. A. (2009) · Diabetes · doi:10.2337/db08-1198 · Cited by 327 · see citing works
Control of Pancreatic β Cell Regeneration by Glucose Metabolism
Porat, S., Weinberg-Corem, N., Tornovsky-Babaey, S., Schyr, R. B., Hija, A., Stolovich-Rain, M., Dadon, D., Granot, Z., Ben-Hur, V., White, P., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.02.012 · Cited by 294 · see citing works
Self-citationPDGF signalling controls age-dependent proliferation in pancreatic β-cells
Chen, H., Gu, X., Liu, Y., Wang, J., Wirt, S. E., Bottino, R., Schorle, H., Sage, J., & Kim, S. K. (2011) · Nature · doi:10.1038/nature10502 · Cited by 278 · see citing works
Emerging models and paradigms for stem cell ageing
Jones, D. L., & Rando, T. A. (2011) · Nature Cell Biology · doi:10.1038/ncb0511-506 · Cited by 256 · see citing works
Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches
Conboy, I. M., & Rando, T. A. (2012) · Cell Cycle · doi:10.4161/cc.20437 · Cited by 239 · see citing works
Liver-derived systemic factors drive β cell hyperplasia in insulin-resistant states
El Ouaamari, A., Kawamori, D., Dirice, E., Liew, C. W., Shadrach, J. L., Hu, J., Katsuta, H., Hollister-Lock, J., Qian, W.-J., Wagers, A. J., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.007 · Cited by 136 · see citing works
Wong, E. S. M., Guezennec, X. L., Demidov, O. N., Marshall, N. T., Wang, S. T., Krishnamurthy, J., Sharpless, N. E., Dunn, N. R., & Bulavin, D. V. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.05.009 · Cited by 124 · see citing works
Levitt, H., Cyphert, T. J., Pascoe, J. L., Hollern, D. A., Abraham, N., Lundell, R. J., Rosa, T., Romano, L., Zou, B., O'Donnell, C. P., et al. (2010) · Diabetologia · doi:10.1007/s00125-010-1919-1 · Cited by 108 · see citing works
Aging and glucose homeostasis in C57BL/6J male mice
Leiter, E. H., Premdas, F. H., Harrison, D. E., & Lipson, L. G. (1988) · The FASEB Journal · doi:10.1096/fasebj.2.12.3044905 · Cited by 93 · see citing works
Glucose and aging control the quiescence period that follows pancreatic beta cell replication
Salpeter, S. J., Klein, A. M., Huangfu, D., Grimsby, J. S., & Dor, Y. (2010) · Development · doi:10.1242/dev.054304 · Cited by 75 · see citing works
Self-citationPancreatic Beta Cells in Very Old Mice Retain Capacity for Compensatory Proliferation
Stolovich-Rain, M., Hija, A., Grimsby, J. S., Gläser, B., & Dor, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.350736 · Cited by 67 · see citing works
Self-citationSalpeter, S. J., Klochendler, A., Weinberg-Corem, N., Porat, S., Granot, Z., Shapiro, A. M. J., Magnuson, M. A., Eden, A., Grimsby, J. S., Gläser, B., et al. (2011) · Endocrinology · doi:10.1210/en.2010-1372 · Cited by 62 · see citing works
Self-citationFinegood, D. T., Weir, G. C., & Bonner‐Weir, S. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.5.e822 · Cited by 50 · see citing works
Molano, R. D., Pileggi, A., Berney, T., Poggioli, R., Zahr, E., Oliver, R., Malek, T. R., Ricordi, C., & Inverardi, L. (2003) · Transplantation · doi:10.1097/01.tp.0000064622.54799.0e · Cited by 44 · see citing works
Song, G., Nguyen, D. T., Pietramaggiori, G., Scherer, S. S., Chen, B., Zhan, Q., Ogawa, R., Yannas, I. V., Wagers, A. J., Orgill, D. P., et al. (2010) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2010.00595.x · Cited by 43 · see citing works
Chen, X., Zhang, X., Chen, F., Larson, C. S., Wang, L.-J., & Kaufman, D. B. (2009) · Transplantation · doi:10.1097/tp.0b013e3181b0d2ee · Cited by 20 · see citing works
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
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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
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
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
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
Elabd, C., Cousin, W., Upadhyayula, P., Chen, R. Y., Chooljian, M. S., Li, J., Kung, S., Jiang, K. P., & Conboy, I. M. (2014) · Nature Communications · doi:10.1038/ncomms5082 · Cited by 411 · 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
Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease
Almada, A. E., & Wagers, A. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.7 · Cited by 315 · see citing works
M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7
Xiao, X., Gaffar, I. M., Guo, P., Wiersch, J. C., Fischbach, S., Peirish, L., Song, Z., El‐Gohary, Y., Prasadan, K. L., Shiota, C., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321347111 · Cited by 311 · see citing works
Targeting the pancreatic β-cell to treat diabetes
Vetere, A., Choudhary, A., Burns, S. M., & Wagner, B. K. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4231 · Cited by 253 · see citing works
Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes
Aguayo‐Mazzucato, C., & Bonner‐Weir, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.007 · Cited by 240 · see citing works
Insulin demand regulates β cell number via the unfolded protein response
Sharma, R. B., O’Donnell, A. C., Stamateris, R. E., Ha, B., McCloskey, K. M., Reynolds, P. R., Arvan, P., & Alonso, L. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79264 · Cited by 202 · see citing works
Diabetes mellitus—advances and challenges in human β-cell proliferation
Wang, P., Fiaschi‐Taesch, N., Vasavada, R. C., Scott, D. K., Garcı́a-Ocaña, A., & Stewart, A. F. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.9 · Cited by 204 · see citing works
Buckley, M. T., Sun, E., George, B. M., Liu, L. A., Schaum, N., Xu, L., Reyes, J. M., Goodell, M. A., Weissman, I. L., Wyss‐Coray, T., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00335-4 · Cited by 189 · see citing works
Liu, J., Li, L., Li, S., Wang, Y., Qin, X., Deng, K., Liu, Y., Zou, K., & Sun, X. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14075 · Cited by 179 · 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
Rejuvenating Strategies for Stem Cell-Based Therapies in Aging
Neves, J., Sousa‐Victor, P., & Jasper, H. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.01.008 · Cited by 156 · see citing works
Age-Related Impairment of Pancreatic Beta-Cell Function: Pathophysiological and Cellular Mechanisms
Tata, V. D. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00138 · Cited by 144 · see citing works
Multi-omic rejuvenation and lifespan extension on exposure to youthful circulation
Zhang, B., Lee, D. E., Trapp, A., Tyshkovskiy, A., Lu, A. T., Bareja, A., Kerepesi, C., McKay, L. K., Shindyapina, A. V., Dmitriev, S. E., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00451-9 · Cited by 134 · 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
Castaño, C., Novials, A., & Párrizas, M. (2018) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3107 · Cited by 104 · see citing works
Functional changes in beta cells during ageing and senescence
Aguayo‐Mazzucato, C. (2020) · Diabetologia · doi:10.1007/s00125-020-05185-6 · Cited by 106 · see citing works
Young capillary vessels rejuvenate aged pancreatic islets
Almaça, J., Molina, J., Drigo, R. A. E., Abdulreda, M. H., Jeon, W. B., Berggren, P., Caicedo, A., & Nam, H. G. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414053111 · Cited by 92 · see citing works
Islet biology, the CDKN2A/B locus and type 2 diabetes risk
Kong, Y., Sharma, R. B., Nwosu, B. U., & Alonso, L. C. (2016) · Diabetologia · doi:10.1007/s00125-016-3967-7 · Cited by 93 · see citing works
Aging and brain rejuvenation as systemic events
Bouchard, J. J., & Villeda, S. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12969 · Cited by 87 · 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
Ximerakis, M., Holton, K. M., Giadone, R. M., Ozek, C., Saxena, M., Santiago, S., Adiconis, X., Dionne, D. A., Nguyễn, L., Shah, K. M., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00373-6 · Cited by 82 · see citing works
The pancreatic β-cell in ageing: Implications in age-related diabetes
Tudurí, E., Soriano, S., Almagro, L., Montanya, E., Alonso‐Magdalena, P., Nadal, Á., & Quesada, I. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101674 · Cited by 87 · see citing works
Johnson, L. A., Zuloaga, K. L., Kugelman, T., Mader, K. S., Morré, J. T., Zuloaga, D. G., Weber, S. J., Marzulla, T., Mulford, A., Button, D. A., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.12.008 · Cited by 73 · see citing works
Liu, A., Guo, E., Yang, J., Yang, Y., Liu, S., Jiang, X., Hu, Q. Z., Dirsch, O., Dahmen, U., Zhang, C., et al. (2017) · Aging Cell · doi:10.1111/acel.12708 · Cited by 70 · see citing works
The systemic environment: at the interface of aging and adult neurogenesis
Smith, L. K., White, C., & Villeda, S. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2715-8 · Cited by 68 · see citing works
A revival of parabiosis in biomedical research
Eggel, A., & Wyss-Coray, T. (2014) · Swiss Medical Weekly · doi:10.4414/smw.2014.13914 · Cited by 67 · see citing works
Advances in β cell replacement and regeneration strategies for treating diabetes
Benthuysen, J. R., Carrano, A. C., & Sander, M. (2016) · Journal of Clinical Investigation · doi:10.1172/jci87439 · Cited by 62 · see citing works
Novel factors modulating human β‐cell proliferation
Shirakawa, J., & Kulkarni, R. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12731 · Cited by 56 · see citing works
A Young Blood Environment Decreases Aging of Senile Mice Kidneys
Huang, Q., Ning, Y., Liu, D., Zhang, Y., Li, D., Zhang, Y., Yin, Z., Fu, B., Cai, G., Sun, X., et al. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx183 · Cited by 56 · see citing works
Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells
Fernandez‐Ruiz, R., García, A., Esteban, Y., Mir-Coll, J., Serra-Navarro, B., Fontcuberta-PiSunyer, M., Broca, C., Armanet, M., Wojtusciszyn, A., Kram, V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19657-1 · Cited by 55 · see citing works
Human Beta Cell Regenerative Drug Therapy for Diabetes: Past Achievements and Future Challenges
Wang, P., Karaköse, E., Choleva, L., Kumar, K., DeVita, R. J., Garcı́a-Ocaña, A., & Stewart, A. F. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.671946 · Cited by 53 · see citing works
Senescent cell accumulation mechanisms inferred from parabiosis
Karin, O., & Alon, U. S. (2020) · GeroScience · doi:10.1007/s11357-020-00286-x · Cited by 55 · see citing works
Guo, T., Liu, T., Sun, Y., Liu, X., Xiong, R., Li, H., Li, Z., Zhang, Z., Tian, Z., & Tian, Y. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1695-x · Cited by 50 · see citing works
Spears, E., Serafimidis, I., Powers, A. C., & Gavalas, A. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.722250 · Cited by 46 · see citing works
The regulation of pre- and post-maturational plasticity of mammalian islet cell mass
Mezza, T., & Kulkarni, R. (2014) · Diabetologia · doi:10.1007/s00125-014-3251-7 · Cited by 44 · see citing works
Histone chaperone ASF1B promotes humanβ-cell proliferation via recruitment of histone H3.3
Paul, P. K., Rabaglia, M. E., Wang, C., Stapleton, D. S., Leng, N., Kendziorski, C. M., Lewis, P. W., Keller, M. P., & Attie, A. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1241914 · Cited by 45 · see citing works
Xiong, Y., Yepuri, G., Necetin, S., Montani, J., Ming, X., & Yang, Z. (2017) · Diabetes · doi:10.2337/db16-1190 · Cited by 45 · see citing works
Tai, G., Ma, Y.-J., Feng, J.-L., Li, J., Qiu, S., Yu, Q., Liu, R.-H., Silumbwe, C. W., Wang, X., Li, X., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae079 · Cited by 44 · see citing works
Blood-Based Therapies to Combat Aging
Castellano, J. M. (2018) · Gerontology · doi:10.1159/000492573 · Cited by 45 · see citing works
Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice
Liu, D., Lun, L., Huang, Q., Ning, Y., Zhang, Y., Wang, L., Yin, Z., Zhang, Y., Xia, L., Yin, Z., et al. (2018) · Kidney International · doi:10.1016/j.kint.2018.03.019 · Cited by 44 · see citing works
Concise Review: New Insights Into the Role of Macrophages in β-Cell Proliferation
Xiao, X., & Gittes, G. K. (2015) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0248 · Cited by 42 · see citing works
Shirakawa, J., Okuyama, T., Yoshida, E., Shimizu, M., Horigome, Y., Tuno, T., Hayasaka, M., Abe, S., Fuse, M., Togashi, Y., et al. (2014) · Endocrinology · doi:10.1210/en.2013-2032 · Cited by 41 · see citing works
Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
Janjuha, S., Singh, S. P., Tsakmaki, A., Mousavy-Gharavy, S. N., Murawala, P., Konantz, J., Birke, S., Hodson, D. J., Rutter, G. A., Bewick, G. A., et al. (2018) · eLife · doi:10.7554/elife.32965 · Cited by 37 · see citing works
Aging insights from heterochronic parabiosis models
Lagunas‐Rangel, F. A. (2024) · npj Aging · doi:10.1038/s41514-024-00166-0 · Cited by 34 · see citing works
The systemic milieu as a mediator of dietary influence on stem cell function during ageing
Murphy, T., & Thuret, S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.004 · Cited by 33 · see citing works
Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease
Horowitz, A. M., & Villeda, S. (2017) · F1000Research · doi:10.12688/f1000research.11437.1 · Cited by 32 · see citing works
Transient Suppression of TGFβ Receptor Signaling Facilitates Human Islet Transplantation
Xiao, X., Fischbach, S., Song, Z., Gaffar, I. M., Zimmerman, R., Wiersch, J. C., Prasadan, K. L., Shiota, C., Guo, P., Ramachandran, S., et al. (2016) · Endocrinology · doi:10.1210/en.2015-1986 · Cited by 32 · see citing works
Tamoxifen suppresses pancreatic β-cell proliferation in mice
Ahn, S.-H., Granger, A., Rankin, M. M., Lam, C. J., Cox, A. R., & Kushner, J. A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0214829 · Cited by 30 · see citing works
Davies, J. S., Thompson, H. L., Pulko, V., Padilla‐Torres, J., & Nikolich‐Žugich, J. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx102 · Cited by 30 · see citing works
Xin, Y., Okamoto, H., Kim, J., Ni, M., Adler, C., Cavino, K., Na, E., Murphy, A. J., Yancopoulos, G. D., Lin, C., et al. (2016) · Endocrinology · doi:10.1210/en.2016-1235 · Cited by 29 · see citing works
Castellano, J. M., Palner, M., Li, S., Freeman, G. M., Nguyen, A., Shen, B., Stan, T. M., Mosher, K. I., Chin, F. T., de Lecea, L., et al. (2016) · Scientific Reports · doi:10.1038/srep29015 · Cited by 28 · see citing works
The Effects of Parabiosis on Aging and Age-Related Diseases
Ashapkin, V. V., Kutueva, L. I., & Vanyushin, B. F. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-42667-5_5 · Cited by 28 · see citing works
Islet Regeneration: Endogenous and Exogenous Approaches
Docherty, F. M., & Sussel, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073306 · Cited by 28 · see citing works
Young plasma attenuates age‐dependent liver ischemia reperfusion injury
Liu, A., Yang, J., Hu, Q. Z., Dirsch, O., Dahmen, U., Zhang, C., Gewirtz, D. A., Fang, H., & Sun, J. (2018) · The FASEB Journal · doi:10.1096/fj.201801234r · Cited by 27 · see citing works
UNC5B Promotes Vascular Endothelial Cell Senescence via the ROS‐Mediated P53 Pathway
Yang, Z. L., Li, H., Luo, P., Yan, D., Yang, N., Zhang, Y., Huang, Y., Liu, Y., Zhang, L., Yan, J., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5546711 · Cited by 27 · see citing works
Impaired regeneration in aged nerves: Clearing out the old to make way for the new
Scheib, J. L., & Höke, A. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.07.010 · Cited by 26 · see citing works
Plasma-Based Strategies for Therapeutic Modulation of Brain Aging
Kheifets, V., & Braithwaite, S. P. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00746-z · Cited by 23 · see citing works
Gonzalez-Armenta, J. L., Li, N., Lee, R.-L., Lu, B., & Molina, A. J. A. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa299 · Cited by 23 · see citing works
The effect of age on stem cell function and utility for therapy
Narbonne, P. (2018) · Cell Medicine · doi:10.1177/2155179018773756 · Cited by 23 · 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
Xiao, X., Chen, C., Guo, P., Zhang, T., Fischbach, S., Fusco, J. C., Shiota, C., Prasadan, K. L., Dong, H. H., & Gittes, G. K. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.770032 · Cited by 22 · see citing works
Young Blood Rejuvenates Old Bodies: A Call for Reflection when Moving from Mice to Men
Hofmann, B. (2018) · Transfusion Medicine and Hemotherapy · doi:10.1159/000481828 · Cited by 22 · see citing works
The rejuvenating influence of young plasma on aged intestine
Ceylani, T., Teker, H. T., Keskin, S., Samgane, G., Açıkgöz, E., & Gurbanov, R. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17926 · Cited by 21 · see citing works
New Trends in Aging Drug Discovery
Benhamú, B., Martín‐Fontecha, M., Vázquez‐Villa, H., López-Rodríguez, M. L., & Ortega‐Gutiérrez, S. (2022) · Biomedicines · doi:10.3390/biomedicines10082006 · Cited by 20 · see citing works
de Lucia, C., Murphy, T., Maruszak, A., Wright, P., Powell, T. R., Hartopp, N., de Jong, S., O'Sullivan, M. J., Breen, G. D., Price, J., et al. (2021) · Aging and Disease · doi:10.14336/ad.2021.0409 · Cited by 16 · see citing works
Rejuvenation of young blood on aging organs: Effects, circulating factors, and mechanisms
Liu, M., Lan, Q., Wu, H., & Qiu, C.-W. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e32652 · Cited by 16 · see citing works
Preventing aging with stem cell rejuvenation: Feasible or infeasible?
Honoki, K. (2017) · World Journal of Stem Cells · doi:10.4252/wjsc.v9.i1.1 · Cited by 16 · see citing works
Proliferating pancreatic beta-cells upregulate ALDH
Liu, Y., Jiang, X., Zeng, Y., Zhou, H., Yang, J., & Cao, R. (2014) · Histochemistry and Cell Biology · doi:10.1007/s00418-014-1248-4 · Cited by 15 · see citing works
Shih, C.-J., Chen, H., Kuo, S., Ou, S., & Chen, Y. (2015) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2015.10.009 · Cited by 15 · see citing works
Ma, J., Gao, B., Zhang, K., Zhang, Q., Jia, G., Li, J., Li, C., Yan, L., & Cai, Z. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.08.004 · Cited by 15 · see citing works
Höving, A. L., Schmidt, K. E., Merten, M., Hamidi, J., Rott, A.-K., Faust, I., Greiner, J. F. W., Gummert, J. F., Kaltschmidt, B., Kaltschmidt, C., et al. (2020) · Cells · doi:10.3390/cells9061472 · Cited by 14 · see citing works
Yin, J., Ibrahim, S. M., Petersen, F., & Yu, X. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.679688 · Cited by 14 · see citing works
A scalable and tunable platform for functional interrogation of peptide hormones in fish
Moses, E., Franěk, R., & Harel, I. (2023) · eLife · doi:10.7554/elife.85960 · Cited by 11 · see citing works
PNA lectin for purifying mouse acinar cells from the inflamed pancreas
Xiao, X., Fischbach, S., Fusco, J. C., Zimmerman, R., Song, Z., Nebres, P., Ricks, D. M., Prasadan, K. L., Shiota, C., Husain, S. Z., et al. (2016) · Scientific Reports · doi:10.1038/srep21127 · Cited by 12 · see citing works
GDF11 and aging biology - controversies resolved and pending
Driss, L. B., Lian, J., Walker, R. G., Howard, J. A., Thompson, T. B., Rubin, L. L., Wagers, A. J., & Lee, R. T. (2023) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.23 · Cited by 13 · see citing works
Beta Cell Regeneration in Adult Mice: Controversy Over the Involvement of Stem Cells
Yu, K., Fischbach, S., & Xiao, X. (2014) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x10666141126113110 · Cited by 12 · see citing works
Mei, J., Liao, S., Liu, Y., Tan, Y.-D., Wang, H., Liang, Y., Dong, X., Song, W., Gan, L., & Deng, S. (2014) · Journal of Diabetes Investigation · doi:10.1111/jdi.12315 · Cited by 12 · see citing works
Endoplasmic Reticulum Stress Induced Proliferation Remains Intact in Aging Mouse β-Cells
Snyder, J. T., Darko, C., Sharma, R. B., & Alonso, L. C. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.734079 · Cited by 11 · see citing works
Yu, C., Zhang, J., Pei, J., Luo, J., Hong, Y., Tian, X., Liu, Z., Zhu, C., Long, C., Shen, L., et al. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122476 · Cited by 10 · see citing works
Xu, S., Qin, D., Yang, H., He, C., Liu, W., Tian, N., Wei, Y., He, X., Hua, J., & Peng, S. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105537 · Cited by 10 · see citing works
Nikolich‐Žugich, J., & Davies, J. S. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12920 · Cited by 9 · see citing works
McPherron, A. C. (2013) · Circulation Research · doi:10.1161/circresaha.113.302239 · Cited by 9 · see citing works
Aitken, T. J., Crabtree, J. E., Jensen, D. M., Hess, K. H., Leininger, B., & Tessem, J. S. (2021) · Biology of the Cell · doi:10.1111/boc.202100035 · Cited by 8 · see citing works
The Role of Blood-Derived Factors in Protection and Regeneration of Aged Tissues
Höving, A. L., Schmidt, K. E., Kaltschmidt, B., Kaltschmidt, C., & Knabbe, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179626 · Cited by 8 · see citing works
Insulin-positive ductal cells do not migrate into preexisting islets during pregnancy
Liu, Q., Jiang, Y., Zhu, L., Qian, J., Wang, C., Yang, T., Prasadan, K. L., Gittes, G. K., & Xiao, X. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00593-z · Cited by 7 · see citing works
Gonzalez-Armenta, J. L., Bergstrom, J., Lee, J., Furdui, C. M., Nicklas, B. J., & Molina, A. J. A. (2023) · GeroScience · doi:10.1007/s11357-023-00855-w · Cited by 6 · see citing works
Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells
Chen, L., Zhang, J., Zhang, Z., Chu, Y., Song, B., & Cai, W. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430146 · Cited by 6 · see citing works
Young blood rejuvenates old brains
Paul, S. M., & Reddy, K. (2014) · Nature Medicine · doi:10.1038/nm.3597 · Cited by 6 · see citing works
Senotherapy for attenuation of cellular senescence in aging and organ implantation
Kang, D. H., Park, Y. S., & Lee, D. Y. (2017) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2017.08.053 · Cited by 6 · see citing works
The disparity of platelet factor 4 and platelets in individuals of different ages
Weng, R., Liu, J., Yu, Q., Yuan, H., Qiu, Y., Liu, H., Wang, L., Mei, Z., & Zhu, F. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34923 · Cited by 5 · see citing works
de Rezende, V. L., da Costa, M. D. A., Martins, C. D., Mathias, K., Gonçalves, C. L., Barichello, T., & Petronilho, F. C. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04361-7 · Cited by 5 · see citing works
Good news for the ageing beta cell
Bender, A. S., & Stewart, A. F. (2013) · Diabetologia · doi:10.1007/s00125-013-3114-7 · Cited by 4 · see citing works
Amico, F., Briggs, G. D., & Balogh, Z. J. (2018) · Medical Hypotheses · doi:10.1016/j.mehy.2018.11.016 · Cited by 4 · see citing works
Liu, Q., Chen, F., Yang, T., Su, J., Song, S., Fu, Z., Li, Y., Hu, Y., & Wang, M. (2021) · Aging and Disease · doi:10.14336/ad.2020.1227 · Cited by 5 · see citing works
- Authors
- Salpeter, S. J., Khalaileh, A., Weinberg-Corem, N., Ziv, O., Glaser, B., & Dor, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Corresponding author
- Dor, Yuval
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-07-17
- Volume
- 62
- Issue
- 8
- Pages
- 2843-2848
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3717843
- OpenAlex
- W2141968536
- Cited by
- 122
- References
- 26
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 9 · 2018: 8 · 2017: 14 · 2016: 15 · 2015: 8 · 2014: 14 · 2013: 3
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- European Commission (241883)
- Hebrew University of Jerusalem
- Israel Science Foundation (41.11)
- Stichting Diabetes Onderzoek Nederland
- Israeli Centers for Research Excellence
- Planning and Budgeting Committee of the Council for Higher Education of Israel
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- aging, type 2 diabetes, heterochronic parabiosis, systemic factors, beta-cell proliferation, p16INK4a, beta cell transplantation
- MeSH terms
- Age Factors, Aging, Animals, Parabiosis, Signal Transduction, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation, Insulin-Secreting Cells, Mice
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