Turning back time
Whether we choose to embrace it or fight against it, ageing is a fundamental and unavoidable part of human life. However for many people ageing doesn’t just bring a slower pace and few extra wrinkles, it brings serious, life-altering degenerative disease.
Thanks to innovative new research into gene expression, this may no longer be the case for future generations. And as an aside, it might also do something about those wrinkles!
University of Exeter Professor of Molecular Genetics, Lorna Harries, has been researching ageing and degenerative disease for more than 20 years and during that time discovered a new mechanism by which cells age.
As we age some cells become what’s known as senescent. Senescent cells differ from others because they eventually stop multiplying but don’t die off when they should. Rather they remain and continue to release chemicals that can negatively impact the healthy cells around them. Ultimately this can affect a person’s ability to fight illness and, depending on where the cells are in the body, can lead to degenerative disease.
Until recently research in this area focused on the removal of such cells, which has been shown to be capable of bringing about ‘rejuvenation’ of function in people and animals. However Lorna and her research team have discovered a new and druggable means to reverse senescence through modulation of RNA splicing. RNA is a nucleic acid present in all living cells and RNA splicing involves the removal or ‘splicing out’ of certain sequences within the cell and then putting them back together in a slightly different way.
Is this the start of being able to live forever?
Lorna says: “When genes are switched on, they produce a message (mRNA), containing the instructions to make whatever the cell requires, and most genes can make more than one type of message depending on the needs of the cell. The decision about what is needed is made by a group of proteins, called splicing factors. These get turned off as we age and that means your cells cannot adapt to their environment, compromising our ability to carry out this ‘fine tuning’ of gene expression. This is a fundamental reason why cells become senescent.
“Our research has demonstrated that restoration of splicing factor levels to those seen in younger cells is able to effectively turn back the ageing clock in old cells, bringing about reversal of senescence.”
This ability to essentially reset ‘failing’ senescent cells could be transformative for many degenerative conditions such as osteoarthritis, hypertension and even dementia. It could eventually provide solutions for almost any disease caused by ageing.
In 2020, along with two partners, Lorna founded SENISCA, a biotech spinout from the University of Exeter that is developing new approaches to reverse this cellular senescence (senotherapeutics).
There are three strands to the work:
#1. Data
Looking at each cell type to determine which messages are driving change in different situations. Essentially developing a ‘bar code’ for each type that other researchers can read in support of further research.
#2. Therapeutics
The team have found 26 targets for their oligonucleotide-based approaches and will be testing the impact treatment can have. Oligonucleotides are short RNA molecules used in genetic testing that tweak how genes are turned on, without interfering with DNA.
#3. Skin
The aesthetic aspect helps to fund future research and development into other areas.
Lorna says “There is huge potential for the future. We will be able to use this to treat, not just the symptoms, but the causes of many degenerative diseases. Ultimately it could even provide a cure for some conditions and may remove the need for things like hip replacements and lung replacements.
“At the moment we are focusing on three main areas – osteoarthritis, Idiopathic Pulmonary Fibrosis (IPF), and age-related macular degeneration. This is because there is a huge unmet clinical need in these areas but also because there are clear ways we can help with our research at this stage. Once we can see impact in these areas we will look to expand into other conditions.”
There’s an element of this research that can sound almost like science fiction. If we can keep resetting cells to be more youthful, will that result in defying the ageing process altogether? Is this the start of being able to live forever?!
“Absolutely not!” says Lorna. “It’s important to remember that this is not about extending life. This is about improving quality of life. Ageing is programmed into all of us, no matter what we are all going to die one day and we are all going to see some deterioration over time. But what might not be inevitable in future are some of the serious degenerative diseases that impact so many people as they age, and that is not just good for individuals but for healthcare services, wider society and the economy as well.”
