The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Human induced pluripotent stem cells free of vector and transgene sequences
Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, I. I., & Thomson, J. A. (2009) · Science · doi:10.1126/science.1172482 · Cited by 2,386
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 1×
“A common feature is the activation of the p53/p21 and p16/ pRb pathways, alteration of cell morphology and metabolism, increase in senescence-associated b-galactosidase (SA-b-Gal) activity, and formation of senescence-associated heterochromatic foci (SAHF) (Narita et al. 2003).”
BackgroundLinking the p53 tumour suppressor pathway to somatic cell reprogramming
Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M., & Belmonte, J. C. I. (2009) · Nature · doi:10.1038/nature08311 · Cited by 1,115
A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
Marión, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., & Blasco, M. A. (2009) · Nature · doi:10.1038/nature08287 · Cited by 1,028 · cited 1×
“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
Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M. A., & Serrano, M. (2009) · Nature · doi:10.1038/nature08290 · Cited by 968
Direct cell reprogramming is a stochastic process amenable to acceleration
Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, C. J., Creyghton, M. P., van Oudenaarden, A., & Jaenisch, R. (2009) · Nature · doi:10.1038/nature08592 · Cited by 938
Immortalization eliminates a roadblock during cellular reprogramming into iPS cells
Utikal, J. S., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G., & Hochedlinger, K. (2009) · Nature · doi:10.1038/nature08285 · Cited by 853
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–400 of 570
Fraile‐Μartinez, O., León-Oliva, D. D., Boaru, D. L., Castro-Martinez, P. D., Montero, C. G., Barrena-Blázquez, S., García-García, J., García‐Honduvilla, N., Álvarez‐Mon, M., López-González, L., et al. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1345459 · Cited by 15
Towards a Novel Frontier in the Use of Epigenetic Clocks in Epidemiology
Martínez‐Magaña, J. J., Hurtado-Soriano, J., Rivero-Segura, N. A., Montalvo‐Ortiz, J. L., Garcia-delaTorre, P., Becerril-Rojas, K., & Gómez-Verján, J. C. (2024) · Archives of Medical Research · doi:10.1016/j.arcmed.2024.103033 · Cited by 13
New Insights into Cell Cycle Regulation and DNA Damage Response in Embryonic Stem Cells
Suvorova, I. I., Katolikova, N. V., & Pospelov, V. A. (2012) · International review of cytology · doi:10.1016/b978-0-12-394310-1.00004-7 · Cited by 14
Huang, C.-S., Lin, H., Lu, K., Wu, W.-W., Yang, Y.-C., Yang, Y., Chiang, C., Hsieh, J.-H., Chang, Y., & Lee, S. (2018) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2018.06.002 · Cited by 13
Hanetseder, D., Levstek, T., Teuschl, A., Frank, J. K., Schaedl, B., Redl, H. R., & Marolt, D. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1214019 · Cited by 13
“Furthermore, cellular reprogramming to hiPSCs allows for epigenetic rejuvenation of the adult cells, thus resulting in mesenchymal progenitors with youthful characteristics (Frobel et al., 2014; Lapasset et al., 2011).”
BackgroundGenetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?
Prytkova, I., Goate, A., Hart, R. P., & Slesinger, P. A. (2018) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13811 · Cited by 12
“Epigenetic reset during conversion of somatic cells to a pluripotent state, even with residual methylation signatures, erases age-related marks (Lapasset et al., 2011) and may have an impact on other epigenetic marks contributing to AUD phenotype.”
BackgroundMechanisms of cellular rejuvenation
Denoth‐Lippuner, A., & Jessberger, S. (2019) · FEBS Letters · doi:10.1002/1873-3468.13483 · Cited by 13
Tanaka, N., Kato, H., Tsuda, H., Sato, Y., Muramatsu, T., Iguchi, A., Nakajima, H., Yoshitake, A., & Senbonmatsu, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186764 · Cited by 12
“reported that by using a cocktail containing genes for the four Yamanaka factors along with NANOG and LIN28 for iPS cell reprogramming, they achieved iPS cell generation from both proliferating fibroblasts and senescent fibroblasts, with similar generative efficiency [10].”
BackgroundMethodThe Potential of iPSCs for the Treatment of Premature Aging Disorders
Compagnucci, C., & Bertini, E. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112350 · Cited by 12
“The rejuvenation of these epigenetic modifications has been demonstrated during cellular reprogramming to pluripotency in vitro [27,32,41,42], but the underlying mechanisms still lack a clear understanding.”
BackgroundSantarella, F., do Amaral, R. J. F. C., Lemoine, M., Kelly, D. C., Cavanagh, B., Marinkovic, M., Smith, A., Garlick, J. A., O’Brien, F. J., & Kearney, C. J. (2022) · Advanced NanoBiomed Research · doi:10.1002/anbr.202200052 · Cited by 12
Phenotyping Neurodegeneration in Human iPSCs
Li, J., & Fraenkel, E. (2021) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-092820-025214 · Cited by 11
Amorós, M. A., Choi, E. S., Cofré, A. H. R., Dokholyan, N. V., & Duzzioni, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.962881 · Cited by 13
“, 2010), and the loss of senescence markers (Lapasset et al., 2011).”
BackgroundChiavellini, P., Lehmann, M., Gallardo, M. D., Canatelli-Mallat, M., Pasquini, D. C., Zoller, J. A., Gordevičius, J., Girard, M., Lacunza, E., Hereñú, C. B., et al. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae071 · Cited by 13
“…itself seems to remain functional during the drift stage in very old mammals as suggested by the fact that somatic cells from old animals or even centenarians respond to rejuvenation genes and undergo full rejuvenation back to age zero, that is, they become induced pluripotent stem cells (20–25).”
BackgroundLemaı̂tre, J.-M. (2024) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.19820 · Cited by 13
“67 These findings demonstrated that rejuvenation of senescent cells and aged cells from centenarians could be achieved through their conversion to the pluripotent state, and that aging was a reversible process.”
BackgroundResultInfluentialKamath, A. M., Ternes, S., McGowan, S. E., English, A. E., Mallampalli, R. K., & Moy, A. B. (2017) · Future Science OA · doi:10.4155/fsoa-2017-0028 · Cited by 11
Asymmetric cell division and replicative aging: a new perspective from the spindle poles
Manzano‐Lopez, J., & Monje-Casas, F. (2020) · Current Genetics · doi:10.1007/s00294-020-01074-y · Cited by 12
Advances in stem cell-derived exosome therapy for radiation-induced skin injury
Kuo, P., Rau, C., & Hsieh, C. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000003004 · Cited by 10
“For example, exosomes from adult MSCs are enriched in anti-inflammatory and pro-angiogenic factors [ 5 , 11 , 12 ] , while exosomes from pluripotent stem cells carry developmentally related microRNAs that can rejuvenate senescent cells [ 5 , 13 , 14 ] .”
Anti-aging strategies and ex vivo organ rejuvenation
Haoui, M., Reddy, P., & Belmonte, J. C. I. (2026) · Cell stem cell · doi:10.1016/j.stem.2025.12.011 · Cited by 11
de Celis, M. F. R., & Bonner‐Weir, S. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1217729 · Cited by 11
“Indeed, Lapasset et al. demonstrated that a six-transcription factor combination generated IPSCs ef fi ciently from senescent fi broblasts (39).”
BackgroundHanetseder, D., Schaedl, B., Redl, H. R., & Marolt, D. (2024) · European Cells and Materials · doi:10.22203/ecm.v047a08 · Cited by 10
Interrogating the regulatory epigenome of cellular senescence
Thanos, D.-F., Ntintas, O. A., Athanasiadis, E. I., Papaspyropoulos, A., Petty, R., & Gorgoulis, V. G. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05848-w · Cited by 10
“In addition to the aforementioned chemical-based strategies, rejuvenation of the transcriptional profile of senescent cells, by using the Yamanaka factors, is also gaining increasing interest [319, 320].”
Establishment of fishing cat cell biobanking for sustainable conservation
Sukparangsi, W., Thongphakdee, A., Karoon, S., Ayuthaya, N. S. N., Hengkhunthod, I., Prakongkaew, R., Bootsri, R., & Sikaeo, W. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.989670 · Cited by 10
“(63), that adding Nanog and Lin28 to Yamanaka factors supports more iPSC induction from senescent human fibroblasts.”
Background3D ECM-Based Scaffolds Boost Young Cell Secretome-Derived EV Rejuvenating Effects in Senescent Cells
Arcuri, S., Pennarossa, G., Iorio, T. D., Gandolfi, F., & Brevini, T. A. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098285 · Cited by 10
“Other approaches involve the induction of a stable [14] or transient [3] pluripotent state for ameliorating cellular and physiological aging hallmarks in senescent or centenarian cells.”
BackgroundВалерьевич, Е. А., Сергеевна, П. А., Ruchko, Y., & Bogomazova, A. N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914408 · Cited by 11
“This suggests that the quality of differentiation can directly affect the phenotype and gene expression in such cells.”
Immunosenescence and Inflamm-Aging: Clinical Interventions and the Potential for Reversal of Aging
Kumar, S. J., Shukla, S., Kumar, S., & Mishra, P. (2024) · Cureus · doi:10.7759/cureus.53297 · Cited by 12
“Targeted therapies for aged immune cells, like rejuvenating aged immune cells with the use of induced pluripotent stem cells (iPSCs) [5], are still being researched.”
BackgroundLuo, C., & Yang, J. (2024) · Aging Cell · doi:10.1111/acel.14285 · Cited by 9
“However, iPSCs have a critical limitation when modeling age-dependent diseases such as HD as they exhibit an embryonic state that fail to retain age-related characteristics (Lapasset et al., 2011; Patterson et al., 2012).”
BackgroundAging: The Mitochondrial Connection
Brown, K. V. (2012) · Journal of Clinical & Experimental Pathology · doi:10.4172/2161-0681.s4-003 · Cited by 11
“Recent work indicates that the process of inducing pluripotency also rejuvenates the energetic capacity of the aged cells, and dramatically improves their mitochondrial function [78,79].”
BackgroundVosough, M., Ravaioli, F., Zabulica, M., Capri, M., Garagnani, P., Franceschi, C., Piccand, J., Kraus, M. R.-C., Kannisto, K., Gramignoli, R., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0215490 · Cited by 10
Chiang, M.-C., & Chern, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052529 · Cited by 10
“Introducing a specific six-factor gene cocktail to an adult somatic cell can reprogram it into an iPSC with reversion of the gene expression profile related to cell senescence [40,57].”
BackgroundPennarossa, G., Iorio, T. D., Arcuri, S., Gandolfi, F., & Brevini, T. A. L. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10438-5 · Cited by 10
“Subsequently, the induced pluripotent stem cell (iPSC) technique [12] was used to reprogram senescent and centenarian cells and re-differentiate them into fully rejuvenated cells [13].”
MethodStem cell aging in adult progeria
Cheung, H., Pei, D., & Chan, W. (2015) · Cell Regeneration · doi:10.1186/s13619-015-0021-z · Cited by 10
“as well [60].”
iPSCs-based anti-aging therapies: Recent discoveries and future challenges
Pareja-Galeano, H., Sanchis‐Gomar, F., Pérez, L. M., Emanuele, E., Lucía, A., Gálvez, B. G., & Gallardo, M. E. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.02.007 · Cited by 10
Iop, L., Sasso, E. D., Schirone, L., Forte, M., Peruzzi, M., Cavarretta, E., Palmerio, S., Gerosa, G., Sciarretta, S., & Frati, G. (2017) · Mediators of Inflammation · doi:10.1155/2017/7953486 · Cited by 10
“induced the pluripotency state in senescent and centenarian fibroblasts, by adding NANOG and LIN28 to the reprogramming gene cocktail used before [129].”
MethodCarvalho, A. B., Coutinho, K. C. D. S., Barbosa, R. A. Q., de Campos, D. B. P., Leitão, I. D. C., Pinto, R. S., dos Santos, D. S., Farjun, B., Araujo, D. S., Mesquita, F., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1077069 · Cited by 10
“Age does not seem to influence the reprograming of cells to a pluripotent state (Lapasset et al., 2011), and Schaniel et al.”
BackgroundAging is a Side Effect of the Ontogenesis Program of Multicellular Organisms
Salnikov, L. (2022) · Biochemistry (Moscow) · doi:10.1134/s0006297922120070 · Cited by 9
“These properties allow such cells to retain a high regenerative potential and make them a target for experiments aimed at rejuvenation [12, 34-37].”
BackgroundHuman iPSCs from Aged Donors Retain Their Mitochondrial Aging Signature
Lejri, I., Cader, M. Z., Grimm, A., & Eckert, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011199 · Cited by 9
“Previous reports have indicated that the use of iPSC technology in aging research may be limited by cellular rejuvenation, resulting in a reset of age markers associated with the source cells [36,37].”
BackgroundZhang, C., Saurat, N. G., Cornacchia, D., Chung, S. Y., Sikder, T., Nemchik, A., Minotti, A. P., Studer, L., & Betel, D. (2025) · Aging Cell · doi:10.1111/acel.70075 · Cited by 14
“We observed robust transcriptional rejuvenation signatures when comparing old primary fibroblasts with their matched iPSC-derived fibroblast counterparts, in agreement with past studies that focused on the rejuvenation of cellular hallmarks of age (Lapasset et al. 2011; Miller et al. 2013).”
InfluentialCell ageing: a flourishing field for neurodegenerative diseases
Brites, D. M. T. O. (2015) · AIMS molecular science · doi:10.3934/molsci.2015.3.225 · Cited by 10
Assoni, A. F., Guerrero, E. N., Wardenaar, R., Oliveira, D., Bakker, P. L., Alves, L. M., Carvalho, V. M., Okamoto, O. K., Zatz, M., & Foijer, F. (2023) · Brain Pathology · doi:10.1111/bpa.13206 · Cited by 8
“As iPSCs rejuvenate as a result of reprogramming [14] and ALS symptoms present with ageing, we expose iPSC-derived motor neurons to oxidative stress to model ageing-associated effects [15].”
BackgroundShort Review: Investigating ARSACS: models for understanding cerebellar degeneration
Artero‐Castro, A., Machuca, C., Jimenez, F. J. R., Jendelová, P., & Erceg, S. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12540 · Cited by 9
Ge, J.-Y., Zheng, Y., Liu, L., Isoda, H., & Oda, T. (2019) · World Journal of Stem Cells · doi:10.4252/wjsc.v11.i9.650 · Cited by 9
Kim, M., Hwang, S., Yoon, J. D., Jeong, Y. W., Kim, E., & Hyun, S. (2020) · Animals · doi:10.3390/ani10101848 · Cited by 9
“Despite the potential of efficient mRNA transfection for reprogramming, cellular senescence served as a fundamental barrier against fully reprogramming fibroblasts from aged dogs to iPSCs [62,63].”
BackgroundPattabiraman, S., & Kaganovich, D. (2014) · BioArchitecture · doi:10.1080/19490992.2015.1014213 · Cited by 9
“iPSC reprogramming technology offers another conceptual window into the mechanism of aging, since reprogramming can effectively “undo” the aging process: it has been suggested that old or even senescent cells can be reprogrammed into “youthful” pluripotent cells.(1,2) This phenomenon demonstrates that aging and associ…”
BackgroundDevelopment of an accelerated cellular model for early changes in Alzheimer’s disease
Xue, H., Gate, S., Gentry, E., Losert, W., & Cao, K. (2023) · Scientific Reports · doi:10.1038/s41598-023-45826-5 · Cited by 8
“However, iPSC-derived neurons can be rejuvenated after reprogramming 42 .”
BackgroundEpigenetic age acceleration and psychosocial stressors in early childhood
Mulligan, C. J. (2025) · Epigenomics · doi:10.1080/17501911.2025.2508684 · Cited by 9
“A seminal study in 2011 demonstrated that fibroblasts from centenarians and other senescent cells could be reprogrammed to induced pluripotent stem cells (iPSCs) [74].”
Brun, C., Allain, C., Ferron, P., Younoussa, H., Colicchio, B., Jeandidier, É., M’kacher, R., Guguen‐Guillouzo, C., & Bertile, F. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2219298120 · Cited by 8
“To some extent, there are similarities with the rejuve-nation process described in hiPS cells from aged human donors when they undergo differentiation into fibroblastic cells (60).”
BackgroundStem Cell Therapy for Diseases of Livestock Animals: An In-Depth Review
Narasimha, R. B., Shreya, S., Anand, V., Yadav, V. K., Rath, P. K., Mishra, B. P., Kancharla, S., Kolli, P., Mandadapu, G., Kumar, S., et al. (2025) · Veterinary Sciences · doi:10.3390/vetsci12010067 · Cited by 9
Cellular reprogramming: A new way to understand aging mechanisms
İlçe, B. Y., Cagin, U., & Yılmazer, A. (2018) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.308 · Cited by 8
“Lapasset et al. (2011) generated iPSCs from senescent fibroblasts by using a six-factor combination and showed downregulated expression of the senescence/aging hallmark proteins, p16INK4A and p21CIP1, similar to hESC lines.”
BackgroundInfluentialGâtinois, V., Desprat, R., Becker, F., Pichard‐Garcia, L., Bernex, F., Isidor, B., Pellestor, F., & Lemaı̂tre, J.-M. (2019) · Stem Cell Research · doi:10.1016/j.scr.2019.101696 · Cited by 8
Self-citationThe potential of human induced pluripotent stem cells for modelling diabetic wound healing in vitro
Martin, P. E., O’Shaughnessy, E. M., Wright, C., & Graham, A. (2018) · Clinical Science · doi:10.1042/cs20171483 · Cited by 10
Transcriptomic reprogramming screen identifies SRSF1 as rejuvenation factorPreprint
Pleşa, A. M., Jung, S., Wang, H. H., Omar, F., Shadpour, M., Buentello, D. C., Pérez-Matos, M. C., Horwitz, N., Cai, G., Ngian, Z., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.13.566787 · Cited by 8
Ivanova, J. S., Shorokhova, M., Pugovkina, N. A., Kozhukharova, I. V., Lp, A., Guriev, N., Kuneev, I. K., Domnina, A. P., Гринчук, Т. М., Zemelko, V. I., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312533 · Cited by 8
Varghese, N., Szabo, L., Cader, M. Z., Lejri, I., Grimm, A., & Eckert, A. (2025) · Communications Biology · doi:10.1038/s42003-025-08152-2 · Cited by 17
Clinical Impact and Mechanisms of Nonatherosclerotic Vascular Aging: The New Kid to Be Blocked
Jouabadi, S. M., Ataabadi, E. A., Golshiri, K., Bos, D., Stricker, B. H. C., Danser, A. H. J., Mattace-Raso, F. U. S., & Roks, A. J. M. (2023) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2023.07.022 · Cited by 8
Reprint of “iPSCs, aging and age-related diseases”
Isobe, K., Cheng, Z., Nishio, N., Suganya, T., Tanaka, Y., & Ito, S. (2014) · New Biotechnology · doi:10.1016/j.nbt.2014.11.002 · Cited by 7
Herberts, C. A., Park, M. V. D. Z., Jwga, P., & de Vries, C. G. J. C. A. (2014) · Cell and Tissue Banking · doi:10.1007/s10561-014-9450-0 · Cited by 6
Chang, W., Wu, Y.-H., Xu, J., & Sung, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051236 · Cited by 7
Direct Cell Conversion of Somatic Cells into Dopamine Neurons: Achievements and Perspectives
Aversano, S., Palladino, R., & Caiazzo, M. (2022) · Cellular Reprogramming · doi:10.1089/cell.2022.0065 · Cited by 7
Towards elucidating disease-relevant states of neurons and glia by CRISPR-based functional genomics
Leng, K., & Kampmann, M. (2022) · Genome Medicine · doi:10.1186/s13073-022-01134-7 · Cited by 7
“Modeling aging in vitro A technical challenge that is inherent to the approach of using hiPSC-derived neural cell types for CRISPR-based screening is the fact that the reprogramming of somatic cells to hiPSCs erases the chromatin alterations associated with aging [101] and that differentiated cells derived from hiPSCs…”
BackgroundiPSCs as a major opportunity to understand and cure age-related diseases
Lemey, C., Milhavet, O., & Lemaı̂tre, J.-M. (2015) · Biogerontology · doi:10.1007/s10522-015-9579-7 · Cited by 10
“Using the same six factor-cocktail, we also succeeded in reprogramming centenarian fibroblasts and demonstrated that cellular aging is not a barrier to reprogramming (Lapasset et al. 2011).”
InfluentialSelf-citationKalies, K., Knöpp, K., Koch, S., Pilowski, C., Wurmbrand, L., & Sedding, D. (2025) · PLoS ONE · doi:10.1371/journal.pone.0319381 · Cited by 7
“This reprogramming has exhibited therapeutic promise and has also indicated the potential to reverse aging-related traits, particularly evident in initial experiments conducted on senescent and centenarian cells [18,19].”
InfluentialAvelar, R. A., Palmer, D. H., Kulaga, A. Y., & Fuellen, G. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102737 · Cited by 11
“During this phase, chromatin architecture undergoes a gradual transition, with somatic identity enhancers – such as ECM-related genes in mouse embryonic fibroblasts – being closed (Li et al., 2017, Schwarz et al., 2018).”
Tavares-Marcos, C., Correia, M., & de Jesus, B. B. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102773 · Cited by 6
“These iPSC demonstrate a reset of telomere length, normalized gene expression patterns, reduced oxidative stress, and improved mitochondrial metabolism, closely resembling human ESCs (Lapasset et al., 2011).”
Rademacher, D. J., Exline, J. E., & Foecking, E. M. (2025) · Biomedicines · doi:10.3390/biomedicines13061400 · Cited by 8
“Incredibly, the senescent and centenarian-derived pluripotent stem cells redifferentiated into fully rejuvenated cells [339].”
Fingelkurts, A. A., & Fingelkurts, A. A. (2023) · Brain Sciences · doi:10.3390/brainsci13030520 · Cited by 7
Romero‐Rodríguez, D. P., Díaz‐Alvarado, C. A., Rocha-González, H. I., & Juárez, E. (2025) · BioFactors · doi:10.1002/biof.2151 · Cited by 7
“87 Combining six reprogramming factors efficiently converted fibroblasts from very old donors into typical induced pluripotent stem cells (iPSCs).”
Charneca, J., Matias, A. C., Escapa, A. L., Fernandes, C., Alves, A., Santos, J. M. A., Nascimento, R., & Bragança, J. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.07.002 · Cited by 6
“Thus, our results indicated that CITED2 supplementation to the cocktail of reprogramming factors may provide constancy to the expression of genes which are critical for the establishment and the maintenance of pluripotency, and may contribute to diminish the epigenetic and gene expression variability observed in iPSC…”
BackgroundGuilbaud, A., Mailliez, A., & Boulanger, É. (2020) · médecine/sciences · doi:10.1051/medsci/2020224 · Cited by 15
Disease Modeling of Neurodegenerative Disorders Using Direct Neural Reprogramming
Legault, E. M., Bouquety, J., & Drouin‐Ouellet, J. (2022) · Cellular Reprogramming · doi:10.1089/cell.2021.0172 · Cited by 7
“…isoforms of protein such as tau) (Sposito et al., 2015; Verheyen et al., 2015), and nuclear transport ( e.g ., reduced RanBP17 protein levels leading to decreased nucleocytoplasmic trafficking effi-ciency) (Lapasset et al., 2011; Mertens et al., 2015, 2018; Qian and Tcw, 2021; Tang et al., 2017).”
Nutritional Modulators of Cellular Senescence In Vitro
Provinciali, M., Pierpaoli, E., Piacenza, F., Giacconi, R., Costarelli, L., Basso, A., Recchioni, R., Marcheselli, F., Bray, D. H., Benlhassan, K., et al. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00022-4 · Cited by 6
Modeling neurodegenerative disorders in adult somatic cells: A critical review
Truong, A. N., Si, E., Duncan, T., & Valenzuela, M. (2016) · Frontiers in Biology · doi:10.1007/s11515-016-1413-3 · Cited by 6
“So what is the “developmental age” of modeled neurons? There remains some debate, not least because age is a multidimensional construct and complicated by reprogamming-related cellular rejuvenation (Marion et al., 2009; Suhr et al., 2010; Lapasset et al., 2011; Mahmoudi and Brunet, 2012; Miller et al., 2013; Vera and…”
BackgroundDeconstructing age reprogramming
Singh, P. B., Laktionov, P. P., & Newman, A. G. (2019) · Journal of Biosciences · doi:10.1007/s12038-019-9923-1 · Cited by 7
hiPSC Disease Modeling of Rare Hereditary Cerebellar Ataxias: Opportunities and Future Challenges
Lukovic, D., Moreno‐Manzano, V., Rodríguez-Jiménez, F. J., Vilches, A., Syková, E., Jendelová, P., Stojković, M., & Erceg, S. (2016) · The Neuroscientist · doi:10.1177/1073858416672652 · Cited by 6
Hemmi, J. J., Mishra, A., & Hornsby, P. J. (2017) · Primate Biology · doi:10.5194/pb-4-153-2017 · Cited by 6
Dannert, A., Schulz, N., Klimmt, J., Knez, L., Groschup, B., Gonçalves, C. C., Carraro, C., Schifferer, M., Brendel, M., & Paquet, D. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.adu9845 · Cited by 6
Seo, B. J., Na, S. B., Choi, J., Ahn, B., Habib, O., Park, C., Hong, K., & Tae, J. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04962-x · Cited by 5
“Mitochondrial function is closely associated with the self-renewal and differentiation abilities of PSCs [16, 17, 28, 49, 68, 70].”
Carr, L. M., Mustafa, S., Care, A., & Collins‐Praino, L. E. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.04.023 · Cited by 5
“…mitochondrial health, nuclear organisation, and protein damage is widely thought to occur during induction to pluripotency (Miller et al., 2013) and has been re-ported across multiple studies on ageing iPSCs (Lapasset et al., 2011; Ocampo et al., 2016) (Prigione et al., 2011; Suhr et al., 2009).”
BackgroundResearch progress of autoimmune diseases based on induced pluripotent stem cells
Ren, R., Jiang, J., Li, X., & Zhang, G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1349138 · Cited by 7
Nakano, Y., & Johmura, Y. (2025) · The Journal of Biochemistry · doi:10.1093/jb/mvae098 · Cited by 7
Comparative analysis of mouse strains for in vivo induction of reprogramming factors
Picó, S., Vílchez-Acosta, A., de Sousa, J. A., Maza, M. D. C. L., Mrabti, C., Parras, A., Desdín-Micó, G., Maroun, C. Y., Branchina, C., von Meyenn, F., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115879 · Cited by 7
Direct Conversion of Cell Fate and Induced Endothelial Cells
Han, J., Shin, Y., & Kim, H.-S. (2021) · Circulation Journal · doi:10.1253/circj.cj-21-0703 · Cited by 5
McCaughey‐Chapman, A., Tarczyluk, M. A., Combrinck, C., Edwards, N., Jones, K., & Connor, B. J. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1003188 · Cited by 7
“Both of these have previously been shown not to be maintained in hiPSCs (Suhr et al., 2010; Lapasset et al., 2011).”
BackgroundDirect Conversion Provides Old Neurons from Aged Donor’s Skin
Koch, P. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.11.009 · Cited by 6
“The reprogramming process itself results inwidespread rejuvenation including epigenetic remodeling and expansion of telomeres (Lapasset et al., 2011; Rohani et al., 2014), and it remains questionable to what extent iPSCderived somatic cells are good models to study age-associated disorders.”
BackgroundResultIn silico clinical trials for anti-aging therapies
Menéndez, J. A., Cuyàs, E., Folguera-Blasco, N., Verdura, S., Martín-Castillo, B., Joven, J., & Alarcón, T. (2019) · Aging · doi:10.18632/aging.102180 · Cited by 5
“(B) Because many of the aging-associated features that are reverted by partial cell reprogramming are related to senescence [25], and given that cellular reprogramming on its own has been shown to rejuvenate senescent cells [52], a combination of senolytic and reprogramming strategies might provide synergistic anti-ag…”
BackgroundClinical & Experimental Pathology
Ren, R., Fedoriw, Y. D., & Willis, M. S. (2012) · Cited by 5
Collagen complexes increase the efficiency of iPS cells generated using fibroblasts from adult mice
Chang, B., Choi, Y., & Kim, J. (2015) · Journal of Reproduction and Development · doi:10.1262/jrd.2014-081 · Cited by 5
“It is well-known that the increase in cellular senescence with age is linked to physiological aging and is characterized by an irreversible cell cycle arrest, such as activation of the p53/p21 and p16/pRb pathway [33].”
BackgroundAge-induced midbrain-striatum assembloids model early phenotypes of Parkinson’s diseasePreprint
Barmpa, K., Saraiva, C., Gomez‐Giro, G., Gabassi, E., Spitz, S., Brandauer, K., Rodriguez-Gatica, J. E., Antony, P. M. A., Robertson, G., Papastefanaki, F., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.28.564305 · Cited by 5
Fountain of youth—Targeting autophagy in aging
Danics, L., Abbas, A. A., Kis, B., & Pircs, K. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1125739 · Cited by 4
A Youthful Touch: Reversal of Aging Hallmarks by Cell Reprogramming
Miliotou, E., & de Lázaro, I. (2024) · Cells Tissues Organs · doi:10.1159/000539415 · Cited by 4
“The effect of reprogramming on telomeres, discussed in the next section, helps reduce chromosomal abnormalities such as aneuploidy, thus contributing to overall genomic stabilization [37, 40].”
InfluentialThe role of glial cells in amyotrophic lateral sclerosis
Pandya, V. A., & Patani, R. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.04.005 · Cited by 5
Stem cell-based therapeutic strategies for liver aging
Niu, H., Wang, Y., Ding, Y. S., Lin, Y., Qin, J., & Wang, J. (2025) · Liver Research · doi:10.1016/j.livres.2025.04.003 · Cited by 4
Vdovin, A. S., Lupatov, A. Y., Kholodenko, I. V., & Yarygin, K. N. (2015) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-015-3112-5 · Cited by 4
Pesaresi, M., Bonilla-Pons, S. A., & Cosma, M. P. (2018) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2018.07.002 · Cited by 4
Böhnke, L., Zhou-Yang, L., Pelucchi, S., Kogler, F., Frantal, D., Schön, F., Lagerström, S., Borgogno, O., Baltazar, J., Herdy, J. R., et al. (2022) · Cellular Reprogramming · doi:10.1089/cell.2021.0200 · Cited by 5
“…pluripotent stem cells (iPSCs), but during reprogramming of human somatic cells into iPSCs, the cells undergo a process of global cellular rejuvenation to early embryonic stages and lose signatures of aging (Lapasset et al., 2011; Miller et al., 2013; Sardo et al., 2017; Takahashi et al., 2007).”
BackgroundSantarella, F., Simpson, C. R., Lemoine, M., McGrath, S., Cavanagh, B., Smith, A., Murphy, C. M., Garlick, J. A., O’Brien, F. J., & Kearney, C. J. (2020) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2020.104174 · Cited by 4
IPSCs, a Promising Tool to Restore Muscle Atrophy
Pareja-Galeano, H., Sanchis‐Gomar, F., Emanuele, E., Gallardo, M. E., & Lucía, A. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25114 · Cited by 4
“Further, senescent and centenarians’ iPSCs can re-differentiate into fully rejuvenated cells (Lapasset et al., 2011).”
BackgroundiPSC reprogramming of fibroblasts from a patient with a Rothmund-Thomson syndrome RTS
Gâtinois, V., Desprat, R., Pichard‐Garcia, L., Becker, F., Goldenberg, A., Balguérie, X., Pellestor, F., & Lemaı̂tre, J.-M. (2020) · Stem Cell Research · doi:10.1016/j.scr.2020.101807 · Cited by 4
Self-citationHolloway, K., Neherin, K., Song, Y., Sato, K., Houston, A., Chen, F., Li, D., & Zhang, H. (2025) · Aging Cell · doi:10.1111/acel.14472 · Cited by 3
“Reprogramming of somatic cells into iPSCs resets the epigenetic landscapes that mark the aging clock (Lapasset et al. 2011; Mahmoudi and Brunet 2012; Marion et al. 2009; Rando and Chang 2012), and consequently cells differentiated from iPSCs resemble fetal cells rather than adult or aged cells…”
Bury, A. G., Olejnik, A., Tocco, C., Saurat, N. G., Stephen, E., Hockemeyer, D. F., Schwamborn, J. C., Studer, L., Mastroberardino, P. G., Bolognin, S., et al. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-01137-2 · Cited by 4
“…is the loss of cellular ageing signatures, including age-associated changes in DNA methylation patterns and histone modi fi cations, and telomere shortening, which can affect the suitability of this approach in modelling certain aspects of cellular ageing and neurodegenerative diseases 140,141 .”
Cao, J., Dong, Q., Du, K., Zhang, M., Chen, W., & Hou, Z. (2026) · Advanced Healthcare Materials · doi:10.1002/adhm.202505203 · Cited by 3
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
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
