Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state
Open accessAbstract
Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible. Thus, we show that our iPSCs generated from senescent and centenarian cells have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESCs. Finally, we show that senescent and centenarian-derived pluripotent stem cells are able to redifferentiate into fully rejuvenated cells. These results provide new insights into iPSC technology and pave the way for regenerative medicine for aged patients.
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Induction of pluripotency in iPSCs resets the age signatures of the donor cells to a fetal stage.
“However, induction of pluripotency in iPSCs resets the age signatures of the donor cells to a fetal stage (7–9).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [7]
In “Resetting telomere function,” the paper reports that aged donor fibroblasts share an aging gene-expression signature, while the six-factor-derived iPSCs cluster with human embryonic stem cells and show reset telomere-related genes. This supports resetting aging signatures through pluripotency, but the paper does not identify the resulting state as fetal; it compares the iPSCs with embryonic stem cells. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSenescent cells from elderly people could be reverted to a pluripotent state only by the additional over-expression of NANOG and LIN2 in addition to Oct3/4, Sox2, c-Myc, and KLF4.
“Of note, senescent cells from elderly people could be reverted to a pluripotent state only by the additional over-expression of NANOG and LIN2 in addition to Oct3/4, Sox2, c-Myc, and KLF4.196”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [196]
Near-senescent or senescent cells can be induced back into a proliferative state.
“A growing body of evidence, including the present study and a prior report of reprogramming of senescent human fibroblasts into induced pluripotent stem cells (iPSCs; ref. 48), suggests that near-senescent or senescent cells can be induced back into a proliferative state.”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [48]
Reprogramming cells from elderly humans (up to 101 years) into pluripotent cells erases many hallmarks of aging and restores youthful gene expression maintained during differentiation.
“Reprogramming cells from elderly humans (as old as 101 years of age) into pluripotent cells erases many of the hallmarks of aging and restores a youthful gene expression profile that is maintained during differentiation (Lapasset et al., 2011; Mertens et al., 2015).”
From The Aging Epigenome (2016) · cites this paper as Lapasset et al., 2011
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Self-citationMulti-omic rejuvenation of human cells by maturation phase transient reprogramming
Gill, D., Parry, A., Santos, F., Okkenhaug, H., Todd, C. D., Hernando-Herraez, I., Stubbs, T. M., Milagre, I., & Reik, W. (2022) · eLife · doi:10.7554/elife.71624 · Cited by 185 · see citing works
“Intriguingly, iPSC reprogramming reverses many age-associated changes including telomere attrition and oxidative stress (Lapasset et al., 2011).”
BackgroundInfluentialp53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes
Mondal, A. M., Horikawa, I., Pine, S. R., Fujita, K., Morgan, K. M., Vera, E., Mazur, S. J., Appella, E., Vojtesek, B., Blasco, M. A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70355 · Cited by 164 · see citing works
“48), suggests that near-senescent or senescent cells can be induced back into a proliferative state.”
High-efficiency RNA-based reprogramming of human primary fibroblasts
Kogut, I., McCarthy, S. M., Pavlova, M., Astling, D. P., Chen, X., Jakimenko, A., Jones, K. L., Getahun, A., Cambier, J. C., Pasmooij, A. M. G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03190-3 · Cited by 165 · see citing works
Tang, Y., Liu, M.-L., Zang, T., & Zhang, C.-L. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00359 · Cited by 151 · see citing works
“This may be due to a lack of the preservation of aging status, since cell reprogramming must transit through an embryo-like pluripotent state accompanied by a loss of particular age-associated features (Lapasset et al., 2011).”
BackgroundHuman induced pluripotent stem cells for modelling neurodevelopmental disorders
Ardhanareeswaran, K., Mariani, J., Coppola, G., Abyzov, A. S., & Vaccarino, F. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.45 · Cited by 160 · see citing works
Turning back time with emerging rejuvenation strategies
Mahmoudi, S., Xu, L., & Brunet, A. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0206-0 · Cited by 163 · see citing works
Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases
Ji, S., Xiong, M., Chen, H., Liu, Y., Zhou, L., Hong, Y., Wang, M., Wang, C., Fu, X., & Sun, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01343-5 · Cited by 166 · see citing works
“Senescent and centenarian cells are revived through pluripotent reprogramming, and the iPSCs produced from these cells have reset telomere length, gene expression profiles, oxidative stress, and mitochondrial metabolism.(267) In addition, the fact that these SCs-derived iPSCs can redifferentiate into fully rejuvenated…”
BackgroundLiu, M.-L., Zang, T., & Zhang, C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.12.018 · Cited by 156 · see citing works
Venables, J. P., Lapasset, L., Gadea, G., Fort, P., Klinck, R., Irimia, M., Vignal, E., Thibault, P., Prinos, P., Chabot, B., et al. (2013) · Nature Communications · doi:10.1038/ncomms3480 · Cited by 140 · see citing works
Self-citationMarolt, D., Traweger, A., Gimona, M., & Redl, H. R. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00352 · Cited by 152 · see citing works
Poetsch, M. S., Strano, A., & Guan, K. (2022) · Stem Cells · doi:10.1093/stmcls/sxac020 · Cited by 144 · see citing works
Tăcutu, R., Budovsky, A., Yanai, H., & Fraifeld, V. E. (2011) · Aging · doi:10.18632/aging.100413 · Cited by 143 · see citing works
“[79] demonstrated that senescent cells and the cells derived from centenarians could be reprogrammed and eventually rejuvenated.”
BackgroundHuman iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature
Spitzhorn, L., Megges, M., Wruck, W., Rahman, M. S., Otte, J., Degistirici, Ö., Meisel, R., Sorg, R. V., Oreffo, R. O. C., & Adjaye, J. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1209-x · Cited by 141 · see citing works
The Information Theory of Aging
Lu, Y. R., Tian, X., & Sinclair, D. A. (2023) · Nature Aging · doi:10.1038/s43587-023-00527-6 · Cited by 141 · see citing works
“Expression of the four Yamanaka factors plus two others, Nanog and LIN28, reprograms senescent and centenarian fibroblasts into iPSCs with the signature of young cells, characteristics that are retained even after they have been converted back to fibroblasts 53 .”
DNA Methylation Clocks and Their Predictive Capacity for Aging Phenotypes and Healthspan
Bergsma, T., & Rogaeva, E. A. (2020) · Neuroscience Insights · doi:10.1177/2633105520942221 · Cited by 137 · see citing works
Direct neuronal reprogramming: learning from and for development
Masserdotti, G., Gascón, S., & Götz, M. (2016) · Development · doi:10.1242/dev.092163 · Cited by 130 · see citing works
“Especially for the latter, direct reprogramming has the advantage of maintaining the age of the starter cell (Mertens et al., 2015), in contrast to the re-setting that occurs when generating induced pluripotent stem cells (Lapasset et al., 2011).”
BackgroundPutting the brakes on the cell cycle: mechanisms of cellular growth arrest
Pack, L. R., Daigh, L. H., & Meyer, T. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.05.005 · Cited by 130 · see citing works
“Finally, genetically reprogramming senescent cells through an iPSC state has recently been demonstrated to ameliorate features of senescence and aging both in vitro and in vivo, suggesting that increased stemness may be a route out of the senescent cell state [79,80].”
BackgroundEpigenetic Regulation of Cellular Senescence
Crouch, J. D., Shvedova, M., Thanapaul, R. J. R. S., Botchkarev, V. A., & Roh, D. S. (2022) · Cells · doi:10.3390/cells11040672 · Cited by 132 · see citing works
“This model has also been utilized in replicatively senescent human donor fibroblasts and human cell line fibroblasts [116].”
MethodMulti‐omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming
Chondronasiou, D., Gill, D., Mosteiro, L., Urdinguio, R. G., Berenguer‐Llergo, A., Aguilera, M., Durand, S., Aprahamian, F., Nirmalathasan, N., Abad, M., et al. (2022) · Aging Cell · doi:10.1111/acel.13578 · Cited by 133 · see citing works
Cellular reprogramming and epigenetic rejuvenation
Simpson, D. J., Olova, N. N., & Chandra, T. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01158-7 · Cited by 123 · see citing works
“morphology, function and number are improved [17, 36, 38, 39].”
Pluripotent stem cells escape from senescence-associated DNA methylation changesPreprint
Koch, C., Reck, K., Shao, K., Lin, Q., Joussen, S., Ziegler, P., Walenda, G., Drescher, W., Opalka, B., May, T., et al. (2012) · Genome Research · doi:10.1101/gr.141945.112 · Cited by 121 · see citing works
“The same holds true for the differentiated progeny of iPSC and ESC, indicating that these cells are not immortalized per se (Lapasset et al. 2011).”
BackgroundInfluentialAlzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
Sala Frigerio, C., & De Strooper, B. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014015 · Cited by 116 · see citing works
“Conversion to iPSCs erases the aging signatures, such as telomere shortening, epigenetic marks of chromatin, and mitochondrial metabolism (Lapasset et al. 2011, Mertens et al. 2015).”
Cellular senescence: Neither irreversible nor reversible
Reimann, M., Lee, S., & Schmitt, C. A. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20232136 · Cited by 120 · see citing works
“When the OSKM reprogramming factors (i.e., Oct4, Sox2, Klf4, and c-Myc) were extended by Nanog and Lin28, senescent cells were readily reprogrammable and presented with a full reversion of their age-related phenotypes (Lapasset et al., 2011).”
BackgroundKim, Y., Zheng, X., Ansari, Z., Bunnell, M. C., Herdy, J. R., Traxler, L., Lee, H., Paquola, A. C. M., Blithikioti, C., Ku, M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.105 · Cited by 117 · see citing works
“Several groups have previously shown that iPSC reprogramming results in clonal cell lines with rejuvenated mitochondria (Lapasset et al., 2011; Prigione et al., 2011; Suhr et al., 2010) and that iPSC-derived neurons lack age-related phenotypes in general (Huh et al.”
BackgroundSenescent Cells: A Therapeutic Target in Cardiovascular Diseases
Suda, M., Paul, K. H., Minamino, T., Miller, J. D., Lerman, A., Ellison, G. M., Tchkonia, T., & Kirkland, J. L. (2023) · Cells · doi:10.3390/cells12091296 · Cited by 116 · see citing works
iPSC Preparation and Epigenetic Memory: Does the Tissue Origin Matter?
Scesa, G., Adami, R., & Bottai, D. (2021) · Cells · doi:10.3390/cells10061470 · Cited by 110 · see citing works
“found that their induction efficiency could be increased using a six-factor reprogramming cocktail (SOX2, OCT4, KLF4, NANOG, LIN28, and c-MYC) instead of the usual OSKM, which also eliminates the marks of cellular aging [82,83].”
BackgroundDrouin‐Ouellet, J., Lau, S., Brattås, P. L., Ottosson, D. R., Pircs, K., Grassi, D. A., Collins, L., Vuono, R., Sjöland, A. A., Westergren‐Thorsson, G., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201607471 · Cited by 105 · see citing works
“…2009; Lee et al , 2009; Lafaille et al , 2012), a number of studies show that reprogramming into pluripotency resets the age of the cells such that the resulting neurons are very young (Maherali et al , 2007; Meissner et al , 2008; Lapasset et al , 2011; Miller et al , 2013; Mertens et al , 2015).”
Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview
Martemucci, G., Portincasa, P., Ciaula, A. D., Mariano, M., Centonze, V., & D‘Alessandro, A. G. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111707 · Cited by 110 · see citing works
Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging
Cheung, H.-H., Liu, X., Canterel-Thouennon, L., Li, L., Edmonson, C., & Rennert, O. M. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.02.006 · Cited by 102 · see citing works
“Reprogramming of normally aged fibroblasts or diseases of laminopathies and Hutchinson-Gilford Progeria syndrome have been reported (Lapasset et al., 2011; Liu et al., 2011; Zhang et al., 2011).”
ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks
Ho, R., Sances, S., Gowing, G., Mathis, M. W., O’Rourke, J. G., Sahabian, A., Wichterle, H., Baloh, R. H., Sareen, D., & Svendsen, C. N. (2016) · Nature Neuroscience · doi:10.1038/nn.4345 · Cited by 101 · see citing works
“This is presumably due to resetting the epigenetic state to that of an embryo during iPSC production, which can occur with samples even over 90-years old [25].”
BackgroundReversal of Hepatocyte Senescence After Continuous In Vivo Cell Proliferation
Wang, M., Chen, F., Li, J., Liu, C.-C., Zhang, H., Xia, Y., Yu, B., You, P., Xiang, D., Lu, L., et al. (2014) · Hepatology · doi:10.1002/hep.27094 · Cited by 103 · see citing works
Alzheimer’s Disease: Mechanism and Approach to Cell Therapy
Amemori, T., Jendelová, P., Růžička, J., Urdzíková, L. M., & Syková, E. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125961 · Cited by 102 · see citing works
“Although they have been successfully generated from cells of a centenarian individual [343,344] and individuals with FAD [345] and SAD [346], they may reset the aging phenotype [347].”
BackgroundNF-κB activation impairs somatic cell reprogramming in ageing
Soria‐Valles, C., Osorio, F. G., Gutiérrez‐Fernández, A., Angeles, A. D. L., Bueno, C., Menéndez, P. R., Martín-Subero, J. I., Daley, G. Q., Freije, J. M. P., & López-Otı́n, C. (2015) · Nature Cell Biology · doi:10.1038/ncb3207 · Cited by 95 · see citing works
RetractedExosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells
Bi, Y., Qiao, X., Cai, Z., Zhao, H., Ye, R., Liu, Q., Gao, L., Liu, Y., Liang, B., Liu, Y., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2024.11.013 · Cited by 98 · see citing works
Aging as an Epigenetic Phenomenon
Ashapkin, V. V., Kutueva, L. I., & Vanyushin, B. F. (2017) · Current Genomics · doi:10.2174/1389202918666170412112130 · Cited by 92 · see citing works
“Neither is it related to the cell senescence, since its correlation to the chronological age is observed in immortal cell lines, such as ESCs.”
BackgroundInfluentialChemical reprogramming for cell fate manipulation: Methods, applications, and perspectives
Wang, J., Sun, S., & Deng, H. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.08.001 · Cited by 91 · see citing works
Senescence-Associated Metabolomic Phenotype in Primary and iPSC-Derived Mesenchymal Stromal Cells
Fernández‐Rebollo, E., Franzen, J., Goetzke, R., Hollmann, J., Ostrowska, A., Oliverio, M., Sieben, T., Rath, B., Kornfeld, J., & Wagner, W. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.12.012 · Cited by 91 · see citing works
“In contrast to primary cells, such as MSCs, induced pluripotent stem cells (iPSCs) do not reveal any signs of replicative senescence (Koch et al., 2013; Lapasset et al., 2011).”
Bajpai, V., Mistriotis, P., Loh, Y., Daley, G., & Andreadis, S. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs253 · Cited by 89 · see citing works
The aging signature: a hallmark of induced pluripotent stem cells?
Rohani, L., Johnson, A. A., Arnold, A., & Stolzing, A. (2013) · Aging Cell · doi:10.1111/acel.12182 · Cited by 88 · see citing works
“Mitochondrial morphology and distribution were also both comparable to ESCs (Lapasset et al., 2011).”
BackgroundResultInfluentialLu, J. Y., Simon, M. A., Zhao, Y., Ablaeva, J., Corson, N., Choi, Y., Yamada, K. Y. H., Schork, N. J., Hood, W. R., Hill, G. E., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.04.011 · Cited by 82 · see citing works
Son, M. J., Kwon, Y., Son, T., & Cho, Y. S. (2016) · Stem Cells · doi:10.1002/stem.2460 · Cited by 85 · see citing works
Chen, W., Tsai, P., Hung, Y., Chiou, S., & Mou, C. (2013) · ACS Nano · doi:10.1021/nn401418n · Cited by 84 · see citing works
Roux, A. E., Zhang, C., Paw, J. S., Zavala‐Solorio, J., Malahias, E., Vijay, T., Kolumam, G. A., Kenyon, C. J., & Kimmel, J. C. (2022) · Cell Systems · doi:10.1016/j.cels.2022.05.002 · Cited by 83 · see citing works
Yagi, T., Kosakai, A., Ito, D., Okada, Y., Akamatsu, W., Nihei, Y., Nabetani, A., Ishikawa, F., Arai, Y., Hirose, N., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041572 · Cited by 82 · see citing works
Reduction of Fibrosis and Scar Formation by Partial Reprogramming In Vivo
Doeser, M. C., Schöler, H. R., & Wu, G. (2018) · Stem Cells · doi:10.1002/stem.2842 · Cited by 78 · see citing works
Anti-Aging Strategies Based on Cellular Reprogramming.
Ocampo, A., Reddy, P., & Belmonte, J. C. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.06.005 · Cited by 77 · see citing works
Lazorthes, S., Vallot, C., Briois, S., Aguirrebengoa, M., Thuret, J., Laurent, G. S., Rougeulle, C., Kapranov, P., Mann, C., Trouche, D., et al. (2015) · Nature Communications · doi:10.1038/ncomms6971 · Cited by 79 · see citing works
Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming
Sun, Z., Kwon, J.-S., Ren, Y., Chen, S., Walker, C. K., Lu, X., Cates, K., Karahan, H., Sviben, S., Fitzpatrick, J. A. J., et al. (2024) · Science · doi:10.1126/science.adl2992 · Cited by 77 · see citing works
“Similarly, LOAD spheroids from six independent individuals exhibited significantly (p 0.05) higher amounts of extracellular A β deposits at PID28 compared to age-matched HC spheroids (Fig.”
InfluentialAssou, S., Bouckenheimer, J., & De Vos, J. (2018) · Stem Cells · doi:10.1002/stem.2797 · Cited by 74 · see citing works
Yang, N., & Sen, P. (2018) · Aging · doi:10.18632/aging.101617 · Cited by 74 · see citing works
Alle, Q., Borgne, E. L., Bensadoun, P., Lemey, C., Béchir, N., Gabanou, M., Estermann, F. E., Bertrand‐Gaday, C., Pessemesse, L., Toupet, K., et al. (2022) · Aging Cell · doi:10.1111/acel.13714 · Cited by 75 · see citing works
“…et al., 2009), we developed an optimized iPSC- derived strategy to rejuvenate senescent cells and cells from centenarians individuals through the pluripotent state, using two additional factors NANOG and LIN28 (OSKMNL), demonstrating that cellular aging was reversible (Lapasset et al., 2011).”
MethodSelf-citationBrun, C., Jean‐Louis, F., Oddos, T., Bagot, M., Bensussan, A., & Michel, L. (2015) · Experimental Dermatology · doi:10.1111/exd.12874 · Cited by 75 · see citing works
Trokovic, R., Weltner, J., Noisa, P., Raivio, T., & Otonkoski, T. (2015) · Stem Cell Research · doi:10.1016/j.scr.2015.06.001 · Cited by 73 · see citing works
“Contrary to what has been observed in mice, donor age was suggested not to impair the reprogramming efficiency of human cells (Somers et al., 2010) and iPSC have been successfully derived even from the fibroblasts of centenarians (Lapasset et al., 2011).”
Cell Therapy Strategies to Combat Immunosenescence
Stahl, E. C., & Brown, B. N. (2015) · Organogenesis · doi:10.1080/15476278.2015.1120046 · Cited by 73 · see citing works
“In addition, the iPSCs were able to redifferentiate into fully rejuvenated cells.(62) Therefore, iPS technology may be the key to the fountain of youth, where any senescent cell could in theory be reborn.”
BackgroundCellular Plasticity: A Route to Senescence Exit and Tumorigenesis
Blander, H. D., Morel, A., Senaratne, A. P., Ouzounova, M., & Puisieux, A. (2021) · Cancers · doi:10.3390/cancers13184561 · Cited by 74 · see citing works
Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution
Francescangeli, F., Angelis, M. L. D., Rossi, R., Cuccu, A., Giuliani, A., Maria, R. D., & Zeuner, A. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10092-4 · Cited by 77 · see citing works
“Moreover, under certain circumstances, senescent cells can re-enter the cell cycle or be reprogrammed into iPSCs [112, 113].”
BackgroundAge Is Relative—Impact of Donor Age on Induced Pluripotent Stem Cell-Derived Cell Functionality
Strässler, E. T., Aalto‐Setälä, K., Kiamehr, M., Landmesser, U., & Kränkel, N. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00004 · Cited by 69 · see citing works
“For instance, nuclear transfer leads to longer telomeres in derived stem cells (54) and seems to erase epigenetic memory better than cellular reprogramming, for NT-SCs are more similar in their DNA methylation patterns to ESCs than iPSCs (38).”
BackgroundInfluentialiPSC technology to study human aging and aging-related disorders
Liu, G., Ding, Z., & Belmonte, J. C. I. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.08.014 · Cited by 69 · see citing works
“Reprogramming toward pluripotency enables resetting of the cellular clock and removal of most, if not all, of the agingassociated cellular hallmarks [72 ,73,74].”
BackgroundProtein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS
Tsekrekou, M., Giannakou, M., Papanikolopoulou, K., & Σκρέτας, Γ. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1383453 · Cited by 69 · see citing works
Induced pluripotent stem cells, a giant leap for mankind therapeutic applications
Bragança, J., Lopes, J. A., Mendes-Silva, L., & Santos, J. M. A. (2019) · World Journal of Stem Cells · doi:10.4252/wjsc.v11.i7.421 · Cited by 67 · see citing works
Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs
Cates, K., McCoy, M. J., Kwon, J.-S., Liu, Y., Abernathy, D. G., Zhang, B., Liu, S., Gontarz, P., Kim, W. K., Chen, S., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2020.08.015 · Cited by 67 · see citing works
Linking Telomere Regulation to Stem Cell Pluripotency
Liu, L. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.10.007 · Cited by 66 · see citing works
Cellular Reprogramming of Human Peripheral Blood Cells
Zhang, X. (2013) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2013.09.001 · Cited by 65 · see citing works
“The generation of iPSCs followed by directed differentiation will not only provide large quantities of patient-specific somatic (stem) cells for individualized therapy, but also raises hopes of rejuvenating cells from elderly patients [96,97].”
Capano, L. S., Sato, C., Ficulle, E., Yu, A., Horie, K., Kwon, J.-S., Burbach, K. F., Barthélemy, N. R., Fox, S. G., Karch, C. M., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.04.018 · Cited by 65 · see citing works
Ageing in the brain: mechanisms and rejuvenating strategies
Gaspar-Silva, F., Trigo, D., & Magalhães, J. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04832-6 · Cited by 75 · see citing works
Khalil, R., Diab‐Assaf, M., & Lemaı̂tre, J.-M. (2023) · Cells · doi:10.3390/cells12060915 · Cited by 66 · see citing works
- Authors
- Lapasset, L., Milhavet, O., Prieur, A., Besnard, E., Babled, A., Aït-Hamou, N., Leschik, J., Pellestor, F., Ramirez, J.-M., De Vos, J., Lehmann, S., & Lemaitre, J.-M.
- Affiliations
- Institut de Génomique Fonctionnelle (FR)
- Hôpital Arnaud de Villeneuve (FR)
- Hôpital Saint Eloi (FR)
- Institut de Génétique Humaine (FR)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-11-01
- Volume
- 25
- Issue
- 21
- Pages
- 2248-2253
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3219229
- OpenAlex
- W2114840727
- Cited by
- 570
- References
- 31
- Citations by year
- 2026: 30 · 2025: 41 · 2024: 46 · 2023: 49 · 2022: 53 · 2021: 49 · 2020: 38 · 2019: 40 · 2018: 49 · 2017: 33 · 2016: 33 · 2015: 30 · 2014: 29 · 2013: 25 · 2012: 23
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-07-BLAN-0076)
- Institut National de la Santé et de la Recherche Médicale
- Institut National Du Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cellular senescence, induced pluripotent stem cells, direct reprogramming, aging, telomere length, oxidative stress, mitochondrial metabolism, gene expression profiles, redifferentiation, rejuvenation, regenerative medicine
- MeSH terms
- Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Line, Cells, Cultured, Humans, Mitochondria, Rejuvenation, Transcription Factors, Mice, SCID, Telomere, Mice, Inbred NOD, Cellular Senescence, Mice, Induced Pluripotent Stem Cells, Cellular Reprogramming
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