Influence of donor age on induced pluripotent stem cells
Open accessAbstract
Induced pluripotent stem cells (iPSCs) are being pursued as a source of cells for autologous therapies, many of which will be aimed at aged patients. To explore the impact of age on iPSC quality, we produced iPSCs from blood cells of 16 donors aged 21-100. We find that iPSCs from older donors retain an epigenetic signature of age, which can be reduced through passaging. Clonal expansion via reprogramming also enables the discovery of somatic mutations present in individual donor cells, which are missed by bulk sequencing methods. We show that exomic mutations in iPSCs increase linearly with age, and all iPSC lines analyzed carry at least one gene-disrupting mutation, several of which have been associated with cancer or dysfunction. Unexpectedly, elderly donors (>90 yrs) harbor fewer mutations than predicted, likely due to a contracted blood progenitor pool. These studies establish that donor age is associated with an increased risk of abnormalities in iPSCs and will inform clinical development of reprogramming technology.
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iN DNA methylation ages reflect the adult and old chronological ages of their donors.
“Clearly, iN DNAm ages reflect the adult and old chronological ages of their donors, whereas pluripotent stem cells and their derivatives reflect pre-natal DNAm ages (Figure 7H; Huh et al., 2016; Kim et al., 2014; Lo Sardo et al., 2017).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Lo Sardo et al., 2017
Pluripotent stem cells and their derivatives reflect pre-natal DNA methylation ages.
“Clearly, iN DNAm ages reflect the adult and old chronological ages of their donors, whereas pluripotent stem cells and their derivatives reflect pre-natal DNAm ages (Figure 7H; Huh et al., 2016; Kim et al., 2014; Lo Sardo et al., 2017).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Lo Sardo et al., 2017
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- Authors
- Lo Sardo, V., Ferguson, W., Erikson, G. A., Topol, E. J., Baldwin, K. K., & Torkamani, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Baldwin, Kristin K
- Torkamani, Ali
- Venue
- Nature Biotechnology
- Published
- 2016-12-12
- Volume
- 35
- Issue
- 1
- Pages
- 69-74
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC5505172
- OpenAlex
- W2566700840
- Cited by
- 223
- References
- 51
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 22 · 2023: 19 · 2022: 20 · 2021: 23 · 2020: 25 · 2019: 25 · 2018: 35 · 2017: 20
- FWCI
- 13.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001114, 8ul1tr000109-05)
- National Institute on Aging (DP1AG055944)
- National Heart, Lung, and Blood Institute (U01HL107436)
- National Institute of Mental Health (R01MH102698)
- National Human Genome Research Institute (U01HG006476)
- National Institute of General Medical Sciences (U54GM114833)
- National Center for Research Resources (UL1RR025774)
- National Center for Advancing Translational Sciences (UL1-TR000109)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- induced pluripotent stem cells, donor age, somatic mutations, clonal expansion, reprogramming, exome sequencing, autologous cell therapy, elderly patients
- MeSH terms
- Adult, Aged, Aging, Cell Differentiation, Cells, Cultured, Chromosome Aberrations, Female, Humans, Male, Middle Aged, Tissue Donors, Stem Cell Transplantation, Epigenesis, Genetic, Young Adult, Induced Pluripotent Stem Cells
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