Scientists Rejuvenate Aged Human Cells

A team of researchers from the Universities of Exeter, Brighton and Oxford has rejuvenated senescent cells to be functionally younger. This discovery builds on earlier findings from the team that showed that genes called splicing factors are progressively switched off as we age, and has the potential to lead to therapies which could help people age better, without experiencing some of the degenerative effects of getting old.

This is a 92 hour time capture image from senescent cultures of human fibroblasts (NHDF) treated with vehicle only controls (DMSO) and 92 hour time capture image showing NHDF cells treated with resveratrol. Image credit: University of Exeter.

This is a 92 hour time capture image from senescent cultures of human fibroblasts (NHDF) treated with vehicle only controls (DMSO) and 92 hour time capture image showing NHDF cells treated with resveratrol. Image credit: University of Exeter.

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 age.

When activated, genes make a message that gives the 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 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.

In the new study, University of Exeter Professor Lorna Harries and colleagues 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.

The scientists applied resveratrol-related compounds (resveralogues), 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.

“This is a first step in trying to make people live normal lifespans, but with health for their entire life,” Professor Harries said.

“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.”

“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,” she added.

“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 aging.”

“Our discovery of cell rejuvenation using these simple compounds shows the enormous potential of aging research to improve the lives of older people,” said co-author Professor Richard Faragher, from the University of Brighton.

The team’s findings were published October 17, 2017 in the journal BMC Cell Biology.

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Eva Latorre et al. 2017. Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC Cell Biology 18 (31); doi: 10.1186/s12860-017-0147-7

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