In recent years, scientists have been able to use skin samples to make any type of body cell, but they have been unable to avoid removing the age-related genetic information first. Now, scientists have found a new technique for creating cells that allows them to maintain their “real” age.
The new technique, which yields cells resembling those found in older people’s brains, will help scientists who are studying age-related diseases like Alzheimer’s and Parkinson’s.
Prof. Rusty Gage, of the Salk Institute’s Laboratory of Genetics in La Jolla, CA, and senior author of the paper, published in Cell Stem Cell, says that keeping age-related signatures in the cells will enable a better understanding of the effects of aging on the brain.
In the past, animal models, ranging from fruit flies to mice, have been used to study the biological consequences of aging in tissue from organs like the brain, for example, that cannot be easily sampled from humans.
More recently, however, stem cells have increasingly been used to study various diseases in humans.
Skin cells can be taken from people and turned into induced pluripotent stem cells, which have the ability to become any cell in the body, if prompted.
This technique has enabled brain cells to be created for the purposes of studying conditions like Alzheimer’s disease; but even when skin cells are taken from an older person, this does not guarantee that stem cells with “older” properties can be produced.
This is because the induced pluripotent stem cell process involves resetting epigenetic signatures in older cells to match younger signatures. Epigenetic signatures are patterns of chemical marks on DNA that dictate what genes are expressed.
This resetting made studying the aging of the human brain difficult, since researchers could not create the characteristics of older brain cells.
Prof. Gage and colleagues decided to try another approach. They turned to an even newer technique that let them convert skin cells directly to neurons, bypassing the stem cell precursor state and creating what is called an induced neuron.
The scientists collected skin cells from 19 people, aged from birth to 89, and prompted them to turn into brain cells using both the induced pluripotent stem cell technique and the direct conversion approach.
The researchers then compared the patterns of gene expression in the resulting neurons with cells taken from autopsied brains.
In the induced pluripotent stem cell method, the patterns in the neurons were the same, regardless of the age of the individual from whom the samples were taken.
But in the brain cells created using the direct conversion technique, there were different patterns of gene expression, depending on whether the samples came from young donors or older adults.
Jerome Mertens, research assistant and one of the co-authors, explains that levels of a nuclear pore protein called RanBP17 were lower in the neurons derived from older patients. The decline of this protein is linked to nuclear transport defects that play a role in neurodegenerative diseases.
“The neurons we derived showed differences depending on donor age. And they actually show changes in gene expression that have been previously implicated in brain aging.”
The team believes that the discovery can help to understand more about physiology and molecular machinery of human nerve cells.
Now that the direct conversion of skin cells to neurons has been shown to retain signatures of age, the researchers expect the technique to become a valuable tool for studying aging. And, while the current work only tested its effectiveness in creating brain cells, they suspect a similar method will enable the creation of aged heart and liver cells as well.
Medical News Today recently reported that stem cell research could make possible a cure for a form of blindness in older people.
Written by Yvette Brazier