WIKIMEDIA, CSIROAfter human somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), the resulting cells retain both genetic and epigenetic indicators of the age of the person who donated the somatic-cell progenitors, scientists have found. Ali Torkamani, Kristin Baldwin, and their colleagues at the Scripps Research Institute in California have found that iPSC genomes have methylation patterns that reflect donor age. In general, the number of mutations those pluripotent cells carry increases with donor age—until around age 90, that is, when the number of mutations decreases, the researchers found. These results, published today (December 12) in Nature Biotechnology, have implications for autologous transplantation—creating a replacement tissue from a patient’s own cells—something that older people are more likely to need, the authors noted.
“If you’re getting cells from these older donors, these seed cells that you use for reprogramming already have some accumulation of mutation load, and so that is actually very important evidence, especially when they are looking at the potential functions of these mutations,” University of California, San Diego, bioengineer Kun Zhang, who was not involved in the study, told The Scientist. Every cell line the researchers examined had at least one mutation in its exomic DNA and some of those mutations were potentially deleterious, even oncogenic, Zhang pointed out. “These damaging mutations might have some unexpected functional consequence when we’re looking at the clinical applications.”
“The study highlights the fact that there is some age-associated risk of pathogenic variants in iPSCs,” Torkamani told The Scientist.
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