Search
Close this search box.

Cellular reprogramming as a tool to model human aging in a dish – Nature Communications

  • Brunet, A. Old and new models for the study of human ageing. Nat. Rev. Mol. Cell Biol. 21, 491–493 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kimura, K. D., Tissenbaum, H. A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946 (1997).

    CAS 
    PubMed 

    Google Scholar
     

  • Howitz, K. T. et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425, 191–196 (2003).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Jones, O. R. et al. Diversity of ageing across the tree of life. Nature 505, 169–173 (2014).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Belsky, D. W. et al. Quantification of biological aging in young adults. Proc. Natl Acad. Sci. USA 112, E4104–E4110 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hamczyk, M. R., del Campo, L. & Andres, V. Aging in the cardiovascular system: lessons from hutchinson-gilford progeria syndrome. Annu Rev. Physiol. 80, 27–48 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • Choi, S. H. et al. A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature 515, 274–278 (2014).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Atchison, L. et al. iPSC-derived endothelial cells affect vascular function in a tissue-engineered blood vessel model of Hutchinson-Gilford progeria syndrome. Stem Cell Rep. 14, 325–337 (2020).

    CAS 

    Google Scholar
     

  • Pitrez, P. R. et al. Vulnerability of progeroid smooth muscle cells to biomechanical forces is mediated by MMP13. Nat. Commun. 11, 4110 (2020).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fernandez-Rebollo, E. et al. Senescence-associated metabolomic phenotype in primary and iPSC-derived mesenchymal stromal cells. Stem Cell Rep. 14, 201–209 (2020).

    CAS 

    Google Scholar
     

  • Ozcebe, S. G., Bahcecioglu, G., Yue, X. S. & Zorlutuna, P. Effect of cellular and ECM aging on human iPSC-derived cardiomyocyte performance, maturity and senescence. Biomaterials 268, 120554 (2021).

    CAS 
    PubMed 

    Google Scholar
     

  • Mertens, J. et al. Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients. Cell Stem Cell 28, 1533–1548.e1536 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Drouin-Ouellet, J. et al. Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson’s disease. Stem Cell Rep. 17, 2203–2219 (2022).

    CAS 

    Google Scholar
     

  • Aguado, J. et al. Inhibition of the cGAS-STING pathway ameliorates the premature senescence hallmarks of Ataxia-Telangiectasia brain organoids. Aging Cell 20, e13468 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Herdy, J. R. et al. Increased post-mitotic senescence in aged human neurons is a pathological feature of Alzheimer’s disease. Cell Stem Cell 29, 1637–1652.e1636 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gatto, N. et al. Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease. Aging Cell 20, e13281 (2021).

    CAS 
    PubMed 

    Google Scholar
     

  • Gladyshev, V. N. et al. Molecular damage in aging. Nat. Aging 1, 1096–1106 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: An expanding universe. Cell 186, 243–278 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Oh, H. S. et al. Organ aging signatures in the plasma proteome track health and disease. Nature 624, 164–172 (2023).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guo, J. et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct. Target Ther. 7, 391 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yazdanyar, A. & Newman, A. B. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin. Geriatr. Med 25, 563–577 (2009).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ugai, T. et al. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat. Rev. Clin. Oncol. 19, 656–673 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • Hayflick, L. & Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621 (1961).

    CAS 
    PubMed 

    Google Scholar
     

  • Liu, D. & Hornsby, P. J. Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res. 67, 3117–3126 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • Liberale, L. et al. Inflammation, aging, and cardiovascular disease: JACC review topic of the week. J. Am. Coll. Cardiol. 79, 837–847 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Eriksson, M. et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423, 293–298 (2003).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • De Sandre-Giovannoli, A. et al. Lamin a truncation in Hutchinson-Gilford progeria. Science 300, 2055 (2003).

    PubMed 

    Google Scholar
     

  • Pitrez, P. R., Rosa, S. C., Praca, C. & Ferreira, L. Vascular disease modeling using induced pluripotent stem cells: Focus in Hutchinson-Gilford Progeria Syndrome. Biochem. Biophys. Res. Commun. 473, 710–718 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • Oshima, J., Sidorova, J. M. & Monnat, R. J. Jr Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev. 33, 105–114 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, R115 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tian, Y. E. et al. Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nat. Med. 29, 1221–1231 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Constantinides, C. et al. Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium. Mol. Psychiatry 28, 1201–1209 (2023).

    PubMed 

    Google Scholar
     

  • Yang, R. et al. A DNA methylation clock associated with age-related illnesses and mortality is accelerated in men with combat PTSD. Mol. Psychiatry 26, 4999–5009 (2021).

    MathSciNet 
    CAS 
    PubMed 

    Google Scholar
     

  • Fries, G. R. et al. Accelerated aging in bipolar disorder: a comprehensive review of molecular findings and their clinical implications. Neurosci. Biobehav Rev. 112, 107–116 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • Singh, V. K., Kalsan, M., Kumar, N., Saini, A. & Chandra, R. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front. Cell Dev. Biol. 3, 2 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lo Sardo, V. et al. Influence of donor age on induced pluripotent stem cells. Nat. Biotechnol. 35, 69–74 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Lapasset, L. et al. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev. 25, 2248–2253 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miller, J. D. et al. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13, 691–705 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vera, E., Bosco, N. & Studer, L. Generating late-onset human iPSC-based disease models by inducing neuronal age-related phenotypes through telomerase manipulation. Cell Rep. 17, 1184–1192 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Acun, A., Nguyen, T. D. & Zorlutuna, P. In vitro aged, hiPSC-origin engineered heart tissue models with age-dependent functional deterioration to study myocardial infarction. Acta Biomater. 94, 372–391 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Odawara, A., Katoh, H., Matsuda, N. & Suzuki, I. Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture. Sci. Rep. 6, 26181 (2016).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ebert, A. et al. Proteasome-dependent regulation of distinct metabolic states during long-term culture of human iPSC-derived cardiomyocytes. Circ. Res 125, 90–103 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Acun, A. & Zorlutuna, P. CRISPR/Cas9 edited induced pluripotent stem cell-based vascular tissues to model aging and disease-dependent impairment. Tissue Eng. Part A 25, 759–772 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sacchetto, C., Vitiello, L., de Windt, L. J., Rampazzo, A. & Calore, M. Modeling cardiovascular diseases with hiPSC-derived cardiomyocytes in 2D and 3D cultures. Int J. Mol. Sci. 21, 3404 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Soria-Valles, C. & Lopez-Otin, C. iPSCs: on the road to reprogramming aging. Trends Mol. Med. 22, 713–724 (2016).

    PubMed 

    Google Scholar
     

  • Chang, A. C. Y. et al. Telomere shortening is a hallmark of genetic cardiomyopathies. Proc. Natl Acad. Sci. USA 115, 9276–9281 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, J. et al. Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy. Nature 572, 335–340 (2019).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reinhardt, P. et al. Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12, 354–367 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Seibler, P. et al. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J. Neurosci. 31, 5970–5976 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rakovic, A. et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J. Biol. Chem. 288, 2223–2237 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Nekrasov, E. D. et al. Manifestation of Huntington’s disease pathology in human induced pluripotent stem cell-derived neurons. Mol. Neurodegener. 11, 27 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koch, P. et al. Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. Nature 480, 543–546 (2011).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Fathi, A. et al. Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration. Aging Cell 21, e13541 (2022).

    CAS 
    PubMed 

    Google Scholar
     

  • Schwab, A. J. et al. Decreased sirtuin deacetylase activity in LRRK2 G2019S iPSC-derived dopaminergic neurons. Stem Cell Rep. 9, 1839–1852 (2017).

    CAS 

    Google Scholar
     

  • Sanchez-Danes, A. et al. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol. Med. 4, 380–395 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cornacchia, D. & Studer, L. Back and forth in time: Directing age in iPSC-derived lineages. Brain Res. 1656, 14–26 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Mertens, J., Reid, D., Lau, S., Kim, Y. & Gage, F. H. Aging in a dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases. Annu. Rev. Genet. 52, 271–293 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gordon, L. B. et al. Association of lonafarnib treatment vs no treatment with mortality rate in patients with Hutchinson-Gilford progeria syndrome. JAMA 319, 1687–1695 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Revechon, G. et al. Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time. Sci. Rep. 7, 4405 (2017).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, G. H. et al. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472, 221–225 (2011).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ribas, J. et al. Biomechanical strain exacerbates inflammation on a progeria-on-a-chip model. Small 13 (2017).

  • Xu, Q. et al. Vascular senescence in progeria: role of endothelial dysfunction. Eur. Heart J. Open 2, oeac047 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Estronca, L. et al. Induced pluripotent stem cell-derived vascular networks to screen nano-bio interactions. Nanoscale Horiz. 6, 245–259 (2021).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Matrone, G. et al. Dysfunction of iPSC-derived endothelial cells in human Hutchinson-Gilford progeria syndrome. Cell Cycle 18, 2495–2508 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lo Cicero, A. et al. Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes. Sci. Rep. 8, 9112 (2018).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nissan, X. et al. Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA. Cell Rep. 2, 1–9 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • Xiong, Z. M., LaDana, C., Wu, D. & Cao, K. An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells. Aging (Albany NY) 5, 288–303 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Blondel, S. et al. Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation. Cell Death Dis. 7, e2105 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Egesipe, A. L. et al. Metformin decreases progerin expression and alleviates pathological defects of Hutchinson-Gilford progeria syndrome cells. NPJ Aging Mech. Dis. 2, 16026 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ivanovska, I. L. et al. Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation. Mol. Biol. Cell 28, 2010–2022 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pacheco, L. M. et al. Progerin expression disrupts critical adult stem cell functions involved in tissue repair. Aging (Albany NY) 6, 1049–1063 (2014).

    PubMed 

    Google Scholar
     

  • Cho, S. et al. Progerin phosphorylation in interphase is lower and less mechanosensitive than lamin-A,C in iPS-derived mesenchymal stem cells. Nucleus 9, 230–245 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Studer, L., Vera, E. & Cornacchia, D. Programming and reprogramming cellular age in the era of induced pluripotency. Cell Stem Cell 16, 591–600 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Blondel, S. et al. Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome. Stem Cells Transl. Med. 3, 510–519 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mertens, J. et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell 17, 705–718 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huh, C. J. et al. Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. Elife 5, e18648 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bersini, S., Schulte, R., Huang, L., Tsai, H. & Hetzer, M. W. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. Elife 9, e54383 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, H., Yang, Y., Liu, J. & Qian, L. Direct cell reprogramming: approaches, mechanisms and progress. Nat. Rev. Mol. Cell Biol. 22, 410–424 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weintraub, H. et al. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc. Natl Acad. Sci. USA 86, 5434–5438 (1989).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mertens, J., Marchetto, M. C., Bardy, C. & Gage, F. H. Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. Nat. Rev. Neurosci. 17, 424–437 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, Y. et al. Mitochondrial aging defects emerge in directly reprogrammed human neurons due to their metabolic profile. Cell Rep. 23, 2550–2558 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quist, E. et al. Transcription factor-based direct conversion of human fibroblasts to functional astrocytes. Stem Cell Rep. 17, 1620–1635 (2022).

    CAS 

    Google Scholar
     

  • Oh, Y. M. et al. Age-related Huntington’s disease progression modeled in directly reprogrammed patient-derived striatal neurons highlights impaired autophagy. Nat. Neurosci. 25, 1420–1433 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Victor, M. B. et al. Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes. Nat. Neurosci. 21, 341–352 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, S. W. et al. Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington’s disease neurodegeneration. Nat. Aging 4, 95–109 (2023).

  • Pircs, K. et al. Distinct subcellular autophagy impairments in induced neurons from patients with Huntington’s disease. Brain 145, 3035–3057 (2022).

    PubMed 

    Google Scholar
     

  • Suzuki, K. et al. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature 540, 144–149 (2016).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, J. R. et al. Efficient prime editing in mouse brain, liver and heart with dual AAVs. Nat. Biotechnol. 42, 253–264 (2024).

  • Zhang, H., Xiong, Z. M. & Cao, K. Mechanisms controlling the smooth muscle cell death in progeria via down-regulation of poly(ADP-ribose) polymerase 1. Proc. Natl Acad. Sci. USA 111, E2261–E2270 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pitrez, P. R. et al. Substrate topography modulates cell aging on a progeria cell model. ACS Biomater. Sci. Eng. 4, 1498–1504 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • Lo, C. Y. et al. An upregulation in the expression of vanilloid transient potential channels 2 enhances hypotonicity-induced cytosolic Ca(2)(+) rise in human induced pluripotent stem cell model of Hutchinson-Gillford Progeria. PLoS ONE 9, e87273 (2014).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pasca, S. P. The rise of three-dimensional human brain cultures. Nature 553, 437–445 (2018).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Kraehenbuehl, T. P., Langer, R. & Ferreira, L. S. Three-dimensional biomaterials for the study of human pluripotent stem cells. Nat. Methods 8, 731–736 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • Fafian-Labora, J. A. & O’Loghlen, A. Classical and nonclassical intercellular communication in senescence and ageing. Trends Cell Biol. 30, 628–639 (2020).

    PubMed 

    Google Scholar
     

  • Borghesan, M. et al. Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence via the interferon protein IFITM3. Cell Rep. 27, 3956–3971.e3956 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Atchison, L., Zhang, H., Cao, K. & Truskey, G. A. A tissue engineered blood vessel model of hutchinson-gilford progeria syndrome using human iPSC-derived smooth muscle cells. Sci. Rep. 7, 8168 (2017).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun, Z. et al. Endogenous recapitulation of Alzheimer’s disease neuropathology through human 3D direct neuronal reprogramming. bioRxiv https://doi.org/10.1101/2023.05.24.542155 (2023).

  • Hofer, M. & Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 6, 402–420 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hu, J. L., Todhunter, M. E., LaBarge, M. A. & Gartner, Z. J. Opportunities for organoids as new models of aging. J. Cell Biol. 217, 39–50 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chesnokova, V. et al. Local non-pituitary growth hormone is induced with aging and facilitates epithelial damage. Cell Rep. 37, 110068 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rai, M. et al. Proteasome stress in skeletal muscle mounts a long-range protective response that delays retinal and brain aging. Cell Metab. 33, 1137–1154.e1139 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shakhbazau, A., Danilkovich, N., Seviaryn, I., Ermilova, T. & Kosmacheva, S. Effects of minocycline and rapamycin in gamma-irradiated human embryonic stem cells-derived cerebral organoids. Mol. Biol. Rep. 46, 1343–1348 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • Park, J. C. et al. A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids. Nat. Commun. 12, 280 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Segel, M. et al. Niche stiffness underlies the ageing of central nervous system progenitor cells. Nature 573, 130–134 (2019).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schuler, S. C. et al. Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality. Cell Rep. 35, 109223 (2021).

    PubMed 

    Google Scholar
     

  • Mansour, A. A. et al. Erratum: an in vivo model of functional and vascularized human brain organoids. Nat. Biotechnol. 36, 772 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • Revah, O. et al. Maturation and circuit integration of transplanted human cortical organoids. Nature 610, 319–326 (2022).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schafer, S. T. et al. An in vivo neuroimmune organoid model to study human microglia phenotypes. Cell 186, 2111–2126.e2120 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Murphy, S. V., De Coppi, P. & Atala, A. Opportunities and challenges of translational 3D bioprinting. Nat. Biomed. Eng. 4, 370–380 (2020).

    PubMed 

    Google Scholar