Old skins cells reprogrammed to regain youthful function
Findings could lead to targeted approach for treating aging.
Date:
April 8, 2022
Source:
Babraham Institute
Summary:
Scientists have developed a new technique for rejuvenating skin
cells.
This technique has allowed researchers to rewind the cellular
biological clock by around 30 years according to molecular measures,
significantly longer than previous reprogramming methods. The
partially rejuvenated cells showed signs of behaving more like
youthful cells in experiments simulating a skin wound. This
research, although in early stages, could eventually have
implications for regenerative medicine, especially if it can be
replicated in other cell types.
FULL STORY ========================================================================== Research from the Babraham Institute has developed a method to 'time
jump' human skin cells by 30 years, turning back the ageing clock for
cells without losing their specialised function. Work by researchers in
the Institute's Epigenetics research programme has been able to partly
restore the function of older cells, as well as rejuvenating the molecular measures of biological age.
The research is published today in the journal eLifeand whilst at an
early stage of exploration, it could revolutionise regenerative medicine.
==========================================================================
What is regenerative medicine? As we age, our cells' ability to function declines and the genome accumulates marks of ageing. Regenerative
biology aims to repair or replace cells including old ones. One of the
most important tools in regenerative biology is our ability to create
'induced' stem cells. The process is a result of several steps, each
erasing some of the marks that make cells specialised. In theory, these
stem cells have the potential to become any cell type, but scientists
aren't yet able to reliably recreate the conditions to re-differentiate
stem cells into all cell types.
Turning back time The new method, based on the Nobel Prize winning
technique scientists use to make stem cells, overcomes the problem of
entirely erasing cell identity by halting reprogramming part of the
way through the process. This allowed researchers to find the precise
balance between reprogramming cells, making them biologically younger,
while still being able to regain their specialised cell function.
In 2007, Shinya Yamanaka was the first scientist to turn normal cells,
which have a specific function, into stem cells which have the special
ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the
Yamanaka factors. The new method, called 'maturation phase transient reprogramming', exposes cells to Yamanaka factors for just 13 days. At
this point, age-related changes are removed and the cells have temporarily
lost their identity. The partly reprogrammed cells were given time to
grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of skin cells (fibroblasts), and this was confirmed by
observing collagen production in the reprogrammed cells.
==========================================================================
Age isn't just a number To show that the cells had been rejuvenated, the researchers looked for changes in the hallmarks of ageing. As explained
by Dr Diljeet Gill, a postdoc in Wolf Reik's lab at the Institute who
conducted the work as a PhD student: "Our understanding of ageing on
a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological
changes in human cells. We were able to apply this to our experiment
to determine the extent of reprogramming our new method achieved."
Researchers looked at multiple measures of cellular age. The first is
the epigenetic clock, where chemical tags present throughout the genome indicate age. The second is the transcriptome, all the gene readouts
produced by the cell. By these two measures, the reprogrammed cells
matched the profile of cells that were 30 years younger compared to
reference data sets.
The potential applications of this technique are dependent on the
cells not only appearing younger, but functioning like young cells
too. Fibroblasts produce collagen, a molecule found in bones, skin tendons
and ligaments, helping provide structure to tissues and heal wounds. The rejuvenated fibroblasts produced more collagen proteins compared to
control cells that did not undergo the reprogramming process. Fibroblasts
also move into areas that need repairing. Researchers tested the partially rejuvenated cells by creating an artificial cut in a layer of cells in
a dish. They found that their treated fibroblasts moved into the gap
faster than older cells. This is a promising sign that one day this
research could eventually be used to create cells that are better at
healing wounds.
In the future, this research may also open up other therapeutic
possibilities; the researchers observed that their method also had an
effect on other genes linked to age-related diseases and symptoms. The
APBA2 gene, associated with Alzheimer's disease, and the MAF gene with
a role in the development of cataracts, both showed changes towards
youthful levels of transcription.
The mechanism behind the successful transient reprogramming is not yet
fully understood, and is the next piece of the puzzle to explore. The researchers speculate that key areas of the genome involved in shaping
cell identity might escape the reprogramming process.
Diljeet concluded: "Our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse
of ageing indicators in genes associated with diseases is particularly promising for the future of this work." Professor Wolf Reik, a group
leader in the Epigenetics research programme who has recently moved
to lead the Altos Labs Cambridge Institute, said: "This work has very
exciting implications. Eventually, we may be able to identify genes
that rejuvenate without reprogramming, and specifically target those to
reduce the effects of ageing. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon."
========================================================================== Story Source: Materials provided by Babraham_Institute. Note: Content
may be edited for style and length.
========================================================================== Journal Reference:
1. Diljeet Gill, Aled Parry, Fa'tima Santos, Hanneke Okkenhaug,
Christopher
D Todd, Irene Hernando-Herraez, Thomas M Stubbs, Ine^s Milagre, Wolf
Reik. Multi-omic rejuvenation of human cells by maturation phase
transient reprogramming. eLife, 2022; 11 DOI: 10.7554/eLife.71624 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220408083901.htm
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