Researchers who looked at the effect of aging on induced pluripotent stem cells (iPSCs) found that genetic mutations increased with the age of the donor who provided the source cells, according to study results published by the journal Nature Biotechnology.
The findings reinforce the importance of screening iPSCs for potentially harmful DNA mutations before using them for therapeutic purposes, said lead investigator.
Researchers found that iPSCs made from donors in their late 80s had twice as many mutations among protein-encoding genes as stem cells made from donors in their early 20s.
That trend followed a predictable linear track paired with age with one exception. Unexpectedly, iPSCs made from blood cells donated by people over 90 years old actually contained fewer mutations than what researchers had expected. In fact, stem cells from those extremely elderly participants had mutation numbers more comparable to iPSCs made from donors one-half to two-thirds younger.
Researchers said the reason for this could be tied to the fact that blood stem cells remaining in elderly people have been protected from mutations over their lifetime by dividing less frequently.
Of the 336 different mutations that were identified in the iPSCs generated for the study, 24 were in genes that could impair cell function or trigger tumor growth if they malfunctioned.
How troublesome these mutations could be depends on how well the stem cells are screened to filter out the defects and how they are used therapeutically, author said. For example, cells made from iPSCs for a bone marrow transplant would be potentially dangerous if they contained a TET2 gene mutation linked to blood cancer, which surfaced during the study.
For the study, researchers tapped three sources for 16 participant blood samples: The Wellderly Study, an ongoing STSI research project that is searching for the genetic secrets behind lifelong health by looking at the genes of healthy elderly people ages 80 to 105; the STSI GeneHeart Study, which involves people with coronary artery disease; and TSRI's research blood donor program.
Aging process increases DNA mutations in stem cells!
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