Principal Investigator: Professor Lorna Harries

Lead institution: University of Exeter

Award amount: £179,222 over 3 years

Members of the research team

 

Following the award of this grant in December 2014, a breakthrough discovery has recently been made and published in BMC Cell Biology

In short:

  • A new way to rejuvenate old cells in the laboratory has been discovered – making the cells not only look younger, but start to behave more like young cells.
  • This has the potential to lead to therapies which could help people age better, without experiencing some of the degenerative effects of ageing.

As we age, our tissues accumulate senescent cells which are alive but do not grow or function as they should. These old cells lose the ability to correctly regulate the output of their genes. This is one reason why tissues and organs become susceptible to disease as we get older.

The researchers synthesised new compounds based on the molecule resveratrol, a substance naturally found in red wine, dark chocolate, red grapes and blueberries, and applied these to cells in culture.  The chemicals caused splicing factors, which are progressively switched off as we age to be switched back on.  Within hours, the cells looked younger and started to rejuvenate, behaving like young cells and dividing.

Dr Eva Latorre, Research Associate at the University of Exeter, who carried out the experiments was surprised by the extent and rapidity of the changes in the cells.   “When I saw some of the cells in the culture dish rejuvenating I couldn’t believe it. These old cells were looking like young cells. It was like magic. I repeated the experiments several times and in each case the cells rejuvenated. I am very excited by the implications and potential for this research.”

This discovery builds on earlier findings from the team in Exeter, which showed that a class of genes called splicing factors are progressively switched off as we age. The Exeter team, together with Professor Richard Faragher and Dr Elizabeth Ostler from the University of Brighton, found that splicing factors can be switched back on with chemicals, making senescent cells not only look younger, but start to behave more like young cells and start dividing.

Splicing factors are crucial in ensuring that genes can perform their full range of functions. One gene can send out several messages to the body to perform a function – such as the decision whether or not to grow new blood vessels – and the splicing factors make the decision about which message to make. As people age, the splicing factors tend to work less efficiently or not at all, restricting the ability of cells to respond to challenges in their environment. Senescent cells, which can be found in most organs from older people, also have fewer splicing factors.

Professor Harries added:   “This demonstrates that when you treat old cells with molecules that restore the levels of the splicing factors, the cells regain some features of youth.  They are able to grow, and their telomeres are now longer, as they are in young cells. Far more research is needed now to establish the true potential for these sorts of approaches to address the degenerative effects of ageing.” 

The co-applicant on the project is Professor David Melzer