Scientists Create 'Old' Brain Cells From Patients' Skin

Scientists have managed to convert skin cells from elderly human donors directly into induced neurone (shown), which have an age signature that could help medical professionals studying Alzheimer's and Parkinson's diseases. Salk Institute

Scientists have grown brain cells with an age signature from human skin cells for the first time—an advance that could help medical professionals in the fight against Alzheimer's and Parkinson's diseases.

The research, published in the journal Cell Stem Cell on Thursday, involved directly converting skin cells taken from 19 subjects, aged between one day and 89 years old, into brain cells.

Previous methods have involved converting skin cells first into induced pluripotent stem (iPS) cells—stem cells that are similar to those found in embryos and are as yet undifferentiated into cells of a specific function. iPS cells can then be differentiated into brain cells, but this process wipes the molecular age signature of the cells clean, so that scientists are not able to study the effects of ageing on the cells. Scientists have previously relied on animal models to study the effects of ageing on cells.

Fred Gage, a geneticist at the Salk Institute for Biological Studies, an independent research institute in California, and the study's senior author, says that being able to study "old" brain cells would allow medical professionals to better understand the risk factors associated with neurodegenerative diseases.

"The greatest risk for Alzheimer's disease, Parkinson's disease and most of these age-related diseases is, in fact, age," says Gage. "In our attempts to model [brain cells] using iPS cells...if we lose the ageing component in there, you are looking at the pure essence of the disease but not at the risk factors of age that contributed to the disease. What we're really looking at is that interface between the disease and how much ageing contributes to it."

Around 850,000 people in the U.K. suffer from Alzheimer's disease, with the number set to rise to one million by 2025, according to the Alzheimer's Society. One in every 500 people has Parkinson's, which equates to about 127,000 people in the U.K. The two diseases are closely related and most commonly occur in older people.

In the study, the researchers compared the two methods of converting skin cells to neuronsvia iPS cells as an intermediary, and via direct conversion. When the skin cells were converted into iPS cells first, the molecular pattern in the neurons made from younger and older subjects were indistinguishable. However, when the direct conversion method was used, older neurons showed a distinctive molecular signature. In fact, the team found the older cells actually expressed lower levels of RanBP17a protein found in the nucleus of cells, decreased levels of which are linked to neurodegenerative diseases. Such differences in gene expressions between older and younger cells could be useful for understanding how neurodegenerative diseases progress.

According to Gage, the technique is currently only laboratory-ready, but he says there is little standing in the way of it being translated to public and private healthcare systems.

He also suggests that, now the technique has been proved in principle, it could be used in the future to create "old" heart or liver cells in order to assess the effects of ageing on these organs.