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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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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Telomere length decreases with age due to cell proliferation in the absence of telomerase enzymes and is restored upon complete iPSC reprogramming (Lapasset et al., 2011).”
From Multi-omic rejuvenation of human cells by maturation phase transient reprogramming (2022) · cites this paper as Lapasset et al., 2011
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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“The rejuvenation of aging hallmarks has been extensively described during cellular reprogramming to pluripotency in vitro (Lapasset et al., 2011;Liu et al., 2011;Mahmoudi and Brunet, 2012;Rando and Chang, 2012), but the dynamics of this process remain poorly understood.”
From In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. (2016) · cites this paper as Lapasset et al., 2011
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“Several groups, including ours, have observed an amelioration of age-associated cellular phenotypes during in vitro cellular reprogramming”
From In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. (2016) · cites this paper as Lapasset et al., 2011
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“iPSC reprogramming reverses many age-associated changes, including telomere attrition and oxidative stress (Lapasset et al., 2011).”
From Multi-omic rejuvenation of human cells by maturation phase transient reprogramming (2022) · cites this paper as Lapasset et al., 2011
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“Early reports using cells derived from old donors to generate iPS cells demonstrated beneficial effects on senescence phenotypes and telomere length [26][27][28] .”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [26]
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“but protocols relied upon rejuvenation through re-differentiation after iPS cell formation 20,26,28 .”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [26]
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“Early experiments in human cells were somewhat encouraging as they provide evidence that some of the biomarkers of aging (that is telomere lengths) were responding to the epigenetic reprogramming”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [26]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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Citations
Cites
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“It has been reported by several groups that cellular senescence is a barrier to reprogramming due to upregulation of p53, p16, and p21, which are also induced by some of the iPSC reprogramming factors (Banito et al. 2009; Kawamura et al. 2009; Li et al. 2009; Marion et al. 2009a; Utikal et al. 2009).”
BackgroundThe Ink4/Arf locus is a barrier for iPS cell reprogramming
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Direct cell reprogramming is a stochastic process amenable to acceleration
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Items 201–300 of 570
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“There has also been a great interest in the use of 3D brain organoids instead of 2D neuronal cells, and the use of CRISPR/cas9 to genetically edit iPSC-derived models, which have been extensively reviewed elsewhere (Korhonen et al. 2018; Lee et al. 2017; Rehbach et al. 2020; Tian et al. 2020).”
BackgroundAlteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS
Günther, R., Pal, A., Williams, C., Zimyanin, V. L., Liehr, M., von Neubeck, C., Krause, M., Parab, M. G., Petri, S., Kalmbach, N., et al. (2022) · Cells · doi:10.3390/cells11071246 · Cited by 32
“It should also be mentioned that iPSC generation leads to rejuvenation of reprogrammed cells [71], which could explain different results as compared to postmortem tissue.”
ResultAversano, S., Caiazza, C., & Caiazzo, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1069482 · Cited by 33
“This result was confirmed by another study showing that the induction of pluripotency can reset the metabolic age of senescent and centenarian cells (Lapasset et al., 2011).”
BackgroundResultRejuvenation of senescent cells—The road to postponing human aging and age-related disease?
Sikora, E. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.09.008 · Cited by 32
Induced Pluripotent Stem Cells in Dermatology: Potentials, Advances, and LimitationsPreprint
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“In addition, the process of reprogramming leads to the “rejuvenation” of fully competent cells as shown by the down-regulation of senescent pathways, elongation of telomeres, and restoration of the mitochondrial function (Marion et al. 2009; Suhr et al. 2009, 2010; Prigione et al. 2010; Lapasset et al. 2011).”
BackgroundInfluentialInduced pluripotent stem cell models of lysosomal storage disorders
Borger, D. K., McMahon, B., Lal, T. R., Serra‐Vinardell, J., Aflaki, E., & Sidransky, E. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.029009 · Cited by 34
“Another limitation is that iPSCderived differentiated cells might not retain aging-associated gene signatures and cellular properties such as senescence and proliferation, mitochondrial metabolism and related oxidative stress (Lapasset et al., 2011; Marion et al., 2009; Prigione et al., 2010; Suhr et al., 2009).”
BackgroundAn update on stem cell biology and engineering for brain development
Parr, C., Yamanaka, S., & Saito, H. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.66 · Cited by 29
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“Despite reprogramming-induced reset of epigenetic dysfunction, cellular senescence [94], transcriptome landscape, telomere size, oxidative stress, and mitochondrial metabolism [95], not all aging-associated hallmarks can be reset.”
BackgroundFathi, A., Mathivanan, S., Kong, L., Petersen, A. J., Harder, C. R. K., Block, J., Miller, J. M., Bhattacharyya, A., Wang, D., & Zhang, S. (2021) · Aging Cell · doi:10.1111/acel.13541 · Cited by 34
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Wandering along the epigenetic timeline
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“For fibroblasts, it has been observed that rejuvenated cells have similar characteristics as young natural fibroblasts cells, such as low levels of oxidative stress [123].”
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“With fewer ethical issues and no signs of replicative senescence, iPSCs exhibit infinite expansion capability without attenuated proliferation, loss of differentiation capability, or telomere attrition [90,91].”
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Anti-senescence therapies: a new concept to address cardiovascular disease
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Progress and challenges in directing the differentiation of human iPSCs into spinal motor neurons
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“The resulting iPS cells were highly proliferative and were capable of expansion for more than 35 passages [51].”
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BackgroundSimple Generation of a High Yield Culture of Induced Neurons from Human Adult Skin Fibroblasts
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“Lapasset et al. (2011) found human iPSCs generated from senescent and centenarian cells have reset much of their cellular physiology to earlier stages and are indistinguishable from human embryonic stem cells.”
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Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan
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“Among these, cellular reprogramming offers a unique prospective for its ability to reset the epigenome and restore multiple aging hallmarks (Conboy et al, 2005; Baker et al, 2011; Lapasset et al, 2011; Longo et al, 2015; Ocampo et al, 2016b; Olova et al, 2019).”
Cell reprogramming: Therapeutic potential and the promise of rejuvenation for the aging brain
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“As mentioned above, induction of pluripotency in adult fibroblasts reverts cellular age to an embryonic stage erasing the epigenetic marks of aging (Lapasset et al., 2011; Patterson et al., 2012).”
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“Other hallmarks of aging including mitochondrial fitness have been shown to be reversed by reprogramming (148, 153).”
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“reprogramming [58–60], and reprogramming processes also induce mitochondrial rejuvenation [21, 61, 62].”
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Rivera‐Mulia, J. C., Schwerer, H., Besnard, E., Desprat, R., Trevilla‐García, C., Sima, J., Bensadoun, P., Zouaoui, A., Gilbert, D. M., & Lemaı̂tre, J.-M. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1491235 · Cited by 21
“H9 and H1 human embryonic stem cells were obtained from the WiCell Research Institute (WI, USA).”
BackgroundMethodInfluentialSelf-citationA comprehensive analysis of induced pluripotent stem cell (iPSC) production and applications
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“…a combination of six OSKMNL factors did not only promote a 10-foldincreaseintheefficiencyoffibroblastreprogrammingcompared to the OSNL combination but also allowed for the successful reprogrammingoffibroblastsobtainedfromolddonors(Baillyetal., 2022; Lapasset et al., 2011; Liao et al., 2008).”
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“It is also of interest that transient (4 days) transfection of a cocktail of mRNAs expressing Oct4, Sox2, Klf4, c-Myc, Lin28, and NANOG (OSKMLN) induced a rapid reversal of cellular aging in human fibroblasts and endothelial cells, in each case without altering cellular identity.”
BackgroundInfluentialRejuvenation by Partial Reprogramming of the Epigenome
Mendelsohn, A. R., Larrick, J. W., & Lei, J. L. (2017) · Rejuvenation Research · doi:10.1089/rej.2017.1958 · Cited by 22
“7 Perhaps the most reductionist view of these results support epigenetic theories of aging, 8–10 whereby instability of the epigenome over time results in diminished cellular function and eventually cellular, tissue, and organ dysfunction that drives aging.”
Is the liver resilient to the process of ageing?
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“It is worth noting here that a combination of “ six-factor gene cocktail ” could ef fi ciently reverse and rejuvenate the senescent fi broblasts derived from centenarian individual by cellular reprogramming [49].”
Cellular Senescence in Cardiovascular Diseases: From Pathogenesis to Therapeutic Challenges
Li, D., Li, Y., Ding, H., Wang, Y., Xie, Y., & Zhang, X. (2023) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd10100439 · Cited by 21
“Furthermore, a groundbreaking study demonstrated that in vivo reprogramming of somatic cells could reinstate their ability to proliferate [160].”
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“Other features pertaining to the original cell persist following reprogramming, such as acquired mutations, DNA damage, epigenetic changes and protein aggregation [121–123].”
BackgroundThe reverse control of irreversible biological processes
Cho, K., Joo, J. I., Shin, D., Kim, D., & Park, S. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1346 · Cited by 20
“In addition to this cellular rejuvenation, aged cells can be reprogrammed by ectopic activation of six transcription factors including Yamanaka’s four cellular reprogramming factors plus Nanog and Lin28.”
The crosstalk between cellular reprogramming and senescence in aging and regeneration
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“However, it was already shown that after reprogramming, the cell resets into a stem-cell state, mostly eliminating this confounding effect [105,106].”
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Zhang, W., Qu, J. T., Suzuki, K., Liu, G., & Belmonte, J. C. I. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.07.001 · Cited by 19
Is aging a barrier to reprogramming? Lessons from induced pluripotent stem cells
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“Most notably, Nanog and Lin28 were used either instead of c-Myc and Klf4 (the Thomson factors) (Yu et al. 2007) or in addition (the six factor cocktail) (Lowry et al. 2008; Lapasset et al. 2011; review in Maherali and Hochedlinger 2008; Okita and Yamanaka 2011; Gonzalez et al. 2011).”
InfluentialSenescence: A program in the road to cell elimination and cancer
Moiseeva, O., Guillon, J., & Ferbeyre, G. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.017 · Cited by 25
Cell-based therapies of liver diseases: age-related challenges
Yarygin, K. N., Lupatov, A., & Kholodenko, I. (2015) · Clinical Interventions in Aging · doi:10.2147/cia.s97926 · Cited by 16
“Later, this point of view concerning human cells became predominant.(11,12,29,30) It was further supported by demonstrating telomere elongation,(31) mitochondria rejuvenation up to the state characteristic of the embryonic stem cells,(32) and enhanced DNA reparation capacity(33,34) in iPSCs, though in different iPSC l…”
BackgroundVasques, J. F., Méndez‐Otero, R., & Gubert, F. (2020) · Regenerative Medicine · doi:10.2217/rme-2020-0067 · Cited by 18
Direct Conversion of Human Fibroblasts to Induced Neurons
Zhou-Yang, L., Eichhorner, S., Karbacher, L., Böhnke, L., Traxler, L., & Mertens, J. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1601-7_6 · Cited by 22
Brondello, J., Prieur, A., Philipot, D., Lemaı̂tre, J.-M., Lenaers, G., Piette, J., & Dulić, V. (2012) · médecine/sciences · doi:10.1051/medsci/2012283017 · Cited by 28
Self-citationBeyret, E., Martínez‐Redondo, P., Platero-Luengo, A., & Belmonte, J. C. I. (2018) · Circulation Research · doi:10.1161/circresaha.117.311866 · Cited by 22
Tamanini, S., Comi, G. P., & Corti, S. P. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0888-0 · Cited by 18
“Reprogramming cells (skin fibroblasts) of centenarians or patients with Hutchinson-Gilford progeria syndrome (HGPS), a disorder characterized by premature aging, resets telomere size, gene expression profiles, and levels of oxidative stress, resulting in the generation of rejuvenated cells ([23]; Liu et al.”
BackgroundHuman Cortical Neuron Generation Using Cell Reprogramming: A Review of Recent Advances
McCaughey‐Chapman, A., & Connor, B. J. (2018) · Stem Cells and Development · doi:10.1089/scd.2018.0122 · Cited by 20
“This has thus far been a challenge, as hiPSCs have been shown to undergo DNA rejuvenation [48].”
Göbel, C., Goetzke, R., Eggermann, T., & Wagner, W. (2018) · Scientific Reports · doi:10.1038/s41598-018-30069-6 · Cited by 19
Cell reprogramming: methods, mechanisms and applications
Zhu, F., & Nie, G. (2025) · Cell Regeneration · doi:10.1186/s13619-025-00229-x · Cited by 26
“…of cases. iPSCs–derived cortical neurons/brain organoids have limited ability to reflect age-associated characteristics due to the finding that the induction of iPSCs from aged donor cells is accompanied by resetting ageing-related traits of donor cells (Lapasset et al. 2011; Miller et al. 2013).”
Wheeler, H. B., Madrigal, A. A., & Chaim, I. A. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2317860121 · Cited by 18
“This is substantiated by research showing, in iPSCs, an increase in telomere length (140), mitochondrial fitness (141), and loss of senescence markers (142), sup - porting the concept of reversal of age - related properties in these cells.”
Hayashi, J., Hashizume, O., Ishikawa, K., & Shimizu, A. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.03.004 · Cited by 17
Age-Related Epigenetic Derangement upon Reprogramming and Differentiation of Cells from the Elderly
Ravaioli, F., Bacalini, M. G., Franceschi, C., & Garagnani, P. (2018) · Genes · doi:10.3390/genes9010039 · Cited by 18
“[22] achieved reprogramming of mitotically inactive cells and fibroblasts deriving from a 101 y.”
BackgroundSogabe, Y., Seno, H., Yamamoto, T., & Yamada, Y. (2018) · Cancer Science · doi:10.1111/cas.13731 · Cited by 17
“Notably, reprogramming by OSKM resets cellular damage‐associated, stress‐associated, and senescence‐associated epigenetic marks in vitro.(68,69,70) Consistently, the reprogramming of cells from elderly humans into pluripotent cells erases many of the hallmarks of aging”
BackgroundEmerging opportunities for induced pluripotent stem cells in orthopaedics
Li, W., Jiao, H., & Walczak, B. E. (2019) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2019.03.001 · Cited by 17
“Ageing cellderived iPSCs were induced to differentiate back to fibroblasts with enhanced capabilities to proliferate at a similar rate as young cells and undergo reduced cellular senescence, resulting in increased population doublings in culture compared with nonreprogrammed parental cells [30].”
BackgroundUmrath, F., Weber, M., Reinert, S., Wendel, H.-P., Avci‐Adali, M., & Alexander, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020587 · Cited by 18
“In the present study, we compared the resulting iMSCs with the originating isogenic JPCs concerning their three-lineage differentiation potential and investigated a potential rejuvenation of iMSCs, which has previously been observed in iPSC-derived cells [10,17].”
BackgroundResultRNA-Based Strategies for Cell Reprogramming toward Pluripotency
Bailly, A., Milhavet, O., & Lemaı̂tre, J.-M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020317 · Cited by 18
“To overcome this barrier, we demonstrated, for the first time, that cell reprogramming can even rejuvenate cells from centenarians and that it can also overcome the barrier of cell senescence without directly inactivating senescence inducers such as p53, p16INK4A and p21CIP1 [38].”
BackgroundInfluentialSelf-citationStudies that shed new light on aging
Katcher, H. L. (2013) · Biochemistry (Moscow) · doi:10.1134/s0006297913090137 · Cited by 17
A cellular identity crisis? Plasticity changes during aging and rejuvenationPreprint
Gorelov, R. A., & Hochedlinger, K. (2024) · Genes & Development · doi:10.1101/gad.351728.124 · Cited by 18
“…plastic as determined by their more efficient reprogramming into induced neurons stands in contrast to a body of work that suggests that aged cells are less efficient at reprogramming into iPSCs (Li et al. 2009; Lapasset et al. 2011; Ravaioli et al. 2018; Grigorash et al. 2023; Yang et al. 2023).”
Turano, P. S., Akbulut, E., Dewald, H. K., Vasilopoulos, T., Fitzgerald-Bocarsly, P., Herbig, U., & Martínez-Zamudio, R. I. (2026) · Cell Reports · doi:10.1016/j.celrep.2025.116795 · Cited by 16
“19,20 Although recent work on the epigenetic regulation of CD8 + T cells during aging has established a correlation between dedicated usage of transcription factors (TFs) to mediate differentiation, aging, and dysfunctional state-specific gene expression programs, 21– 24 the gene-regulatory…”
Implications of Cellular Aging in Cardiac Reprogramming
Passaro, F., & Testa, G. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00043 · Cited by 15
“Also, the gene expression profile of these cells confirmed they had been reset to an embryonic-like stage (19, 58, 64, 67).”
BackgroundCreating stem cell‐derived neuromuscular junctions in vitro
Luttrell, S. M., Smith, A. S. T., & Mack, D. L. (2021) · Muscle & Nerve · doi:10.1002/mus.27360 · Cited by 17
“tent state may not retain the epigenetic and phenotypic features of aged cells.(95-97) Furthermore, iPSC-derived motor neurons are functionally immature and must undergo lengthy culture times to achieve mature cell traits.”
BackgroundA new insight into cell biological and biochemical changes through aging
Sahabi, S., Jafari-Gharabaghlou, D., & Zarghami, N. (2022) · Acta Histochemica · doi:10.1016/j.acthis.2021.151841 · Cited by 16
Guerrero, A., Innes, A. J., Roux, P., Buisman, S. C., Jung, J., Ortet, L., Moiseeva, V., Wagner, V., Robinson, L. J., Ausema, A., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00279-9 · Cited by 15
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
Cary, W., Hori, C. N., Pham, M. T., Nacey, C., McGee, J., Hamou, M., Berman, R. F., Bauer, G., Nolta, J. A., & Waldau, B. (2015) · World Neurosurgery · doi:10.1016/j.wneu.2015.05.076 · Cited by 16
Arnold, F., Mahaddalkar, P. U., Kraus, J. M., Zhong, X., Bergmann, W., Srinivasan, D., Gout, J., Roger, E., Beutel, A. K., Zizer, E., et al. (2021) · Advanced Science · doi:10.1002/advs.202100626 · Cited by 18
Tsitkov, S., Valentine, K., Kozareva, V., Donde, A., Frank, A. P., Lei, S., Workman, M. J., Lim, R. G., Wu, J., Wu, Z., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47758-8 · Cited by 17
“On the other hand, iPSC-derived motor neurons are expected to exhibit the characteristicsof a ‘ younger ’ cell, with reversed senescence due to reprogramming 33 .”
Chien, Y., Huang, C.-S., Lin, H.-C., Lu, K., Tsai, P., Lai, Y.-H., Chen, K.-H., Lee, S., Huang, Y., & Wang, C. (2017) · Oncotarget · doi:10.18632/oncotarget.23603 · Cited by 15
“has reported a protocol using a combination of six-factor Oct4/Sox2/Klf4/c-Myc/Lin28/ Nanog to improve iPSC reprogramming efficiency of senescent fibroblasts from aged donors [12].”
BackgroundMethodGâtinois, V., Desprat, R., Becker, F., Pichard‐Garcia, L., Bernex, F., Corsini, C., Pellestor, F., & Lemaı̂tre, J.-M. (2019) · Stem Cell Research · doi:10.1016/j.scr.2019.101515 · Cited by 15
“, 2015 and transcriptomic analysis was performed on fibroblasts BJ (Fibro BJ), fibroblasts from GEO Samples GSM1566208 (Fibro CCA and CCB), iPS derived from BJ fibroblasts with 4 reprogramming factors OSKM or 6 factors OSKMNL (Lapasset et al., 2011), respectively (IPSC BJ 4F and iPSC BJ 6F) and the corresponding Embry…”
MethodSelf-citationNeurodegeneration in a dish: advancing human stem-cell-based models of Alzheimer’s disease
Klimmt, J., Dannert, A., & Paquet, D. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.01.008 · Cited by 16
Human-induced pluripotent stem cells as a model for studying sporadic Alzheimer’s disease
Riemens, R. J. M., Kenis, G., & van den Beucken, T. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107318 · Cited by 16
“Third, reprogramming somatic cells into iPSCs has been associated with loss of aging traits such as certain epigenetic chromatin marks, telomerase shortening and altered mitochondrial metabolism (Lapasset et al., 2011; Mertens et al., 2015).”
BackgroundValderhaug, V. D., Heiney, K., Ramstad, O. H., Bråthen, G., Kuan, W., Nichele, S., Sandvig, A., & Sandvig, I. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00413.2020 · Cited by 13
Multitasking Microglia and Alzheimer’s Disease: Diversity, Tools and Therapeutic Targets
Grubman, A., Kanninen, K. M., & Malm, T. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0825-5 · Cited by 14
“Whereas iPS cells become rejuvenated and lose their epigenetic information upon reprogramming (Lapasset et al. 2011), direct conversion of fibroblasts or blood monocytes to microglia may be a preferable model for studying human microglia activation in the context of AD.”
BackgroundHuman iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging
Chao, C., Shen, P.-W., Tzeng, T., Kung, H., Tsai, T., & Wong, Y. (2021) · Biomedicines · doi:10.3390/biomedicines9111635 · Cited by 13
Gudenschwager, C., Chavez, I., Cárdenas, C., & González-Billault, C. E. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5586052 · Cited by 12
“On the contrary, iPSC-derived neurons restore their telomere size during the reprogramming to pluripotency, and it becomes indistinguishable from those of embryonic stem cells [7, 92].”
BackgroundInfluentialBoyling, A., Pérez‐Siles, G., & Kennerson, M. L. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.842860 · Cited by 15
“iPSC reprogramming reverts mature cells back to a pluripotent embryonic state (Lapasset et al., 2011), and subsequent differentiation protocols attempt to mirror in vivo developmental processes to produce the desired cell type (Zhu and Huangfu, 2013).”
BackgroundEffects of lifespan-extending interventions on cognitive healthspan
Čulig, L., Sahbaz, B. D., & Bohr, V. A. (2022) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.36 · Cited by 14
Walczak, B. E., Jiao, H., Lee, M., & Li, W. (2021) · Cartilage · doi:10.1177/19476035211040858 · Cited by 15
Endothelial cell direct reprogramming: Past, present, and future
Cho, S., Aakash, P., Lee, S., & Yoon, Y. (2023) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2023.04.006 · Cited by 14
Chromatin: the old and young of it
Emerson, F. J., & Lee, S. S. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1270285 · Cited by 15
Making Sense of Extreme Longevity: Explorations Into the Spiritual Lives of Centenarians
Manning, L. K., Leek, J., & Radina, M. E. (2012) · Journal of Religion Spirituality & Aging · doi:10.1080/15528030.2012.706737 · Cited by 14
Singh, S., Srivastava, A., Srivastava, P., Dhuriya, Y. K., Pandey, A., Kumar, D., & Rajpurohit, C. S. (2016) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2016.00072 · Cited by 14
Regulation of Age-related Decline by Transcription Factors and Their Crosstalk with the Epigenome
Zhou, X., Sen, I., Lin, X.-X., & Riedel, C. G. (2018) · Current Genomics · doi:10.2174/1389202919666180503125850 · Cited by 15
“Furthermore, the Yamanaka factors (Oct3/4, Sox2, Klf4 and c-Myc), which can substantially alter the epigenome of highly differentiated cells to induce a pluripotent state, have been shown to ameliorate aging phenotypes in vitro [184] and in vivo [185] through partial epigenetic reprogramming.”
BackgroundTranscriptomic reprogramming for neuronal age reversal
Pleşa, A. M., Shadpour, M., Boyden, E. S., & Church, G. M. (2023) · Human Genetics · doi:10.1007/s00439-023-02529-1 · Cited by 13
Paine, P. T., Rechsteiner, C., Morandini, F., Desdín-Micó, G., Mrabti, C., Parras, A., Haghani, A., Brooke, R., Horvath, S., Seluanov, A., et al. (2024) · Frontiers in Aging · doi:10.3389/fragi.2023.1323194 · Cited by 13
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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