Compounds AP39, AP123, RT01 may reverse ageing in human cell: Study

Scientists have developed a novel compound which they say can reverse ageing in human cells, and may lead to  “anti-degenerative” drugs.

In a laboratory study of endothelial cells - which line the inside of blood vessels - researchers at the University of Exeter in the UK tested compounds designed to target mitochondria, the “power stations” of cells.

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The compounds - AP39, AP123 and RT01 - have been designed to selectively deliver minute quantities of the gas hydrogen sulphide to the mitochondria in cells and help the old or damaged cells to generate the ‘energy’ needed for survival and to reduce senescence.

In the samples used, the number of senescent cells - older cells that have deteriorated and stopped dividing - was reduced by up to 50 per cent.

The team also identified two splicing factors  - a component of cells - that play a key role in when and how endothelial cells become senescent.

The findings raise the possibility of future treatments not only for blood vessels - which become stiffer as they age, raising the risk of problems including heart attacks and strokes - but also for other cells, researchers said.

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“As human bodies age, they accumulate old (senescent) cells that do not function as well as younger cells,” said Professor Lorna Harries, of the University of Exeter Medical School.

“This is not just an effect of ageing - it is a reason why we age,” said Harries.

“The compounds developed at Exeter have the potential to tweak the mechanisms by which this ageing of cells happens,” she said.

“We used to think age-related diseases like cancer, dementia and diabetes each had a unique cause, but they actually track back to one or two common mechanisms.

“This research may well be the basis for a new generation of anti-degenerative drugs, Harries said.

The research looked at precisely targeting and rejuvenating mitochondria in old cells.

Each one of our genes is capable of making more than one product, and splicing factors are the genes that make the decision about which of these products are made.

“Nearly half of the aged cells we tested showed signs of rejuvenating into young cell models,” said Harries.

Using novel chemicals, the researchers were able to very specifically target two splicing factors (SRSF2 or HNRNPD) that play a key role in determining how and why our cells change with advancing age.

The researchers tested three different compounds and found each produced a 40-50 per cent drop in the number of senescent blood vessel cells.

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“Our compounds provide mitochondria in cells with an alternative fuel to help them function properly,” said Professor Matt Whiteman, also from the University of Exeter.

“Many disease states can essentially be viewed as accelerated ageing, and keeping mitochondria healthy helps either prevent or, in many cases using animal models, reverse this,” Whiteman said.