A new way to rejuvenate old cells in the laboratory…
making them not only look younger, but start to function more like young cells, has been uncovered. The discovery has the potential to lead to therapies which could help people age better, without experiencing some of the degenerative effects of getting old.
A research team has discovered a new way to rejuvenate inactive senescent cells. Within hours of treatment the older cells started to divide, and had longer telomeres – the ‘caps’ on the chromosomes which shorten as we age.
The discovery, led Professor Lorna Harries, Professor of Molecular Genetics at the University of Exeter, builds on earlier findings from the research team that showed that a class of genes called splicing factors are progressively switched off as we age. The researchers found that splicing factors can be switched back on with chemicals, making senescent cells not only look physically younger, but start to behave more like young cells and start dividing.
This is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts.
The researchers applied compounds called reversatrol analogues, chemicals based on a substance naturally found in red wine, dark chocolate, red grapes and blueberries, 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.
The research was published in the journal, BMC Cell Biology.
The discovery has the potential to lead to therapies which could help people age better, without experiencing some of the degenerative effects of getting old. Most people by the age of 85 have experienced some kind of chronic illness, and as people get older they are more prone to stroke, heart disease and cancer.
Harries said: “This is a first step in trying to make people live normal lifespans, but with health for their entire life. Our data suggests that using chemicals to switch back on the major class of genes that are switched off as we age might provide a means to restore function to old cells.”
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,” she said. “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.”
In the paper, the team concludes, “We propose therefore that splicing factors, and the upstream drivers of splicing factor expression may prove promising as druggable targets to ameliorate ageing phenotypes and hold promise as anti-degenerative compounds effective in human cells in the future.”
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.
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 – the caps on the ends of the chromosomes that shorten as we age – are now longer, as they are in young cells. Far more research is needed now to establish the true potential for these sort of approaches to address the degenerative effects of ageing. ”