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Ageing Increases DNA Mutations In Important Stem Cells

Ageing might be causing numerous DNA mutations in an important type of stem cell, says a new study published in the journal Nature Biotechnology.

We all know that ageing sucks—the body is no more as it used to be, neither inside nor outside. A new study provides further insight into the changes that occur during the process. The authors of the paper (researchers from the Scripps Translational Science Institute (STSI) and The Scripps Research Institute (TSRI)) looked into how ageing affects induced pluripotent stem cells (iPSCs); these cells were obtained from source cells provided by donors. Stem cells constitute a very important set of cells as they are able to differentiate into specialized cell types; this is why iPSCs can be used for treatment of diseases to generate specialised cells as needed by patients: for instance, iPSCs can be precursors for cells to be used for a transplant of tissues.

The iPSCs that were examined were found to have undergone genetic mutations, an effect which increased with age; those coming from donors who were in their late 80s had two times more mutations than those from much younger donors (individuals in their 20s).

“Any time a cell divides, there is a risk of a mutation occurring. Over time, those risks multiply,” says co-lead author, Ali Torkamani. “Our study highlights that increased risk of mutations in iPSCs made from older donors of source cells.”

Torkamani and his team explain that their findings show the paramount importance of testing donated iPSCs before they are used for therapeutic purposes.

“Using iPSCs for treatment has already been initiated in Japan in a woman with age-related macular degeneration,” says co-author Eric Topol. “Accordingly, it’s vital that we fully understand the effects of aging on these cells being cultivated to treat patients in the future.”

The team identified 336 mutations in the iPSCs. 24 of these were found in genes that could lead to cell function impairment or tumour growth. This could be very dangerous if donated iPSCs are not screened for these mutations: for example, if they happen to contain gene mutations associated with blood cancer, but are used for a bone marrow transplant, the patient receiving them will be dangerously at risk.

On the other hand, interestingly, iPSCs coming from even older adults are more comparable to those of younger people. When the ones donated by individuals in their 90s were analysed, it was found that the mutations were similar in number to what was spotted in young adults (donors in their early 20s).


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