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Reprogram, rejuvenate, rewind: spinout

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Soaking up Longevity – a Stanford University team has rejuvenated aging human cells with a novel protein “bath” and formed a spinout.

Researchers at Stanford University have reprogrammed human cells back a youthful state by harnessing the power of Yamanaka factors* and are hopeful that progress towards cures for aging diseases such as osteoarthritis and muscle wasting will result. The team has formed a spinout company, Turn Biotechnologies, with the aim of developing therapies.

Longevity.Technology: Understanding – and then altering – the genetic reasons for aging is a key area of Longevity research. There are multiple pathways to be mapped, but if they can be used to slow, halt or even reverse aging, therapies for numerous age-related conditions could be developed.

The epigenome is the raft of proteins that both package the DNA in our cells and control access to our genes. Errors in the epigenome build up over time (reducing the cell’s efficiency) are thought to be one of the major contributory factors of aging.

Embryonic stem cells have the ability to become any sort of body cell – whether that’s a brain neuron, a skin cell or a heart muscle cell. What they become is determined by a set of chemical markers tagged on their epigenome.

These markers enable access to the genes that the cell type will need, but block-off access to unnecessary genes – a heart muscle cell can’t access the genes used by neurons to relay information, for example. As aging occurs, this permission/blocking system becomes degraded and the cell’s ability to function properly is impeded.

Yamanaka factors are often used to transform an adult cell into induced pluripotent stem cells, or iPS cells – cells that can be nudged to become any sort of cell. These have become important tools in Longevity research, but they are a double-edged sword, as over-exposure can lead to a cell’s identity being erased.

The Stanford research team took a novel approach in using the Yamanaka factors to avoid this erasure. The cells were removed, and then maintained in cultures containing small amounts of the factors – enough to reprogram the cells’ epigenome, but not enough to reprogram the entire cell to the point of oblivion.


“…we can promote rejuvenation in multiple human cell types”


 

The cells were found to have retained their identities after the procedure, but also to have been rejuvenated to a youthful state.

Lead researcher Dr Vittorio Sebastiano said: “When iPS cells are made from adult cells, they become both youthful and pluripotent. We’ve wondered for some time if it might be possible to simply rewind the aging clock without inducing pluripotency. Now we’ve found that, by tightly controlling the duration of the exposure to these protein factors, we can promote rejuvenation in multiple human cell types [1].”

The researchers found that aged cartilage cells from patients suffering from osteoarthritis no longer secreted the inflammatory factors that provoke the disease and that human muscle stem cells that had been impaired by muscle-wasting disease, could be restored to vigour [2].

The team has formed a spinout company, Turn Biotechnologies, with the aim of developing therapies for osteoarthritis and other diseases.


 

* Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem cells, and their over-expression can induce pluripotency in human somatic cells.

[1] https://www.eurekalert.org/pub_releases/2020-03/sm-ohc032220.php
[2] https://www.nature.com/articles/s41467-020-15174-3

Image credit: Angel GlenPixabay
Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.
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