Slow down aging by deriving blood vessel cells from skin cells

According to the latest study, scientists have successfully created blood vessels from used skin cells called fibroblasts from young and old patients. As per the description given in the journal eLife on September 8, 2020, the clues behind the aging of blood vessels have been released. The research has also helped researchers in identifying new molecular targets to slow the aging process in vascular cells.

“The vasculature is extremely important for aging but its impact has been underestimated because it has been difficult to study how these cells age,” says Martin Hetzer, the senior author of the paper and Salk’s Vice President and Chief Science Officer.

It is observed that when the blood vessel cells are created from the induced pluripotent stem cells, there are no age-related molecular changes visible. This means that all the knowledge about the aging of blood vessel cells has been gained by observing changes like veins and arteries becoming less elastic, thickening, and stiffening over time. These changes result in increased blood pressure and risk of heart disease.

In 2015, Salk President Rusty Gage along with his team including Hetzer reprogrammed the fibroblasts directly into neurons. The brain cells were able to retain their markers of age which led to another study on how neurons change with age.

Later, Hetzer and his colleagues applied the same direct-conversion approach to creating two types of vascular cells. One of the cells i.e. vascular endothelial cells that made up the inner lining of blood vessels whereas the other smooth muscle cells surrounded the endothelial cells.

“We are among the first to use this technique to study the aging of the vascular system,” says Roberta Schulte, the Hetzer lab coordinator and co-first author of the paper. “The idea of developing both of these cell types from fibroblasts was out there, but we tweaked the techniques to suit our needs.”

The skin cells were collected from three young donors aged 19 to 30, three older donors aged 62 to 87, and 8 patients with Hutchinson-Gilford Progeria Syndrome to be induced with VECs and SMCs which showed clear signatures of age. The results showed how and why blood vessels change with age and confirmed that the direct-conversion method helped in retaining any age-related changes.

Followed by these observations, researchers tested if blocking BMP4 protein could treat aging blood vessels. It was observed that antibodies blocking BMP4 lowered levels of vascular leakiness in smooth muscle cells from donors with vascular disease.

This led to new therapeutic targets that could treat both progeria and normal age-related changes occurring in the human vascular system.

“By repeating what was done with neurons, we’ve demonstrated that this direct reprogramming is a powerful tool that can likely be applied to many cell types to study aging mechanisms in all sorts of other human tissues,” says Hetzer, holder of the Jesse and Caryl Phillips Foundation Chair.

The team is planning to expand its studies to explore the exact molecular mechanisms followed by the genes in controlling the changes seen in the vasculature. These are the same genes that were found to change with age.