8th November 2017

Old human cells rejuvenated in aging breakthrough

In yet another breakthrough for aging research, a new way to rejuvenate old cells in the laboratory has been discovered, making them not only look younger, but start to behave more like young cells.

Researchers at the University of Exeter have found 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 ends of chromosomes that shorten as we age. This discovery builds on earlier findings from the Exeter group that showed how a class of genes called "splicing factors" are progressively switched off as we age. The Exeter team, working 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 physically younger, but start to actually behave more like young cells and start dividing.

The researchers applied compounds called resveratrol analogues – chemicals based on a substance naturally found in red wine, dark chocolate, red grapes and blueberries – to cells in culture. These chemicals caused splicing factors to be switched back on. Within hours, the cells looked younger and started to rejuvenate, behaving like young cells and dividing.

The researchers say their discovery could lead to therapies for helping 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.

“This is a first step in trying to make people live normal lifespans, but with health for their entire life,” said Lorna Harries, Professor of Molecular Genetics at the University of Exeter. “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.”

Chemicals used in the study – resveratrol analogues. Credit: Eva Latorre et al.

Dr Eva Latorre, Research Associate at the University of Exeter, 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.”

As we age, our tissues accumulate senescent cells. These are alive, but do not grow or function as they should. These old "zombie 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 age. When activated, genes make a message giving instructions for the cell to behave in a certain way. Most genes can make more than one message, which determines how the cell acts.

Splicing factors are crucial in ensuring that genes perform their full range of functions. One gene can send out several messages to the body – such as the decision whether or not to grow new blood vessels – and splicing factors decide which message to send. 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 – 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 aging.”

“At a time when our capacity to translate new knowledge about the mechanisms of aging into medicines and lifestyle advice is limited only by a chronic shortage of funds, older people are ill-served by self-indulgent science fiction,” said Professor Richard Faragher of the University of Brighton. “They need practical action to restore their health and they need it yesterday. Our discovery of cell rejuvenation using these simple compounds shows the enormous potential of aging research to improve the lives of older people.”

The team's paper is published in the journal BMC Cell Biology.

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