Cellular senescence in human cells. Credit: Eva Latorre
Newly discovered compounds could help reduce cell aging and lead to a new generation of anti-degeneration drugs.
A team from the University of Exeter has developed new compounds designed that have shown the ability to reduce the number of senescent cells—older cells that have deteriorated and stopped dividing—by up to 50 percent.
The findings could yield future treatments for blood vessels, which become stiffer as they age and raise the risk of heart attacks and strokes, as well as treatments for other cells.
“As human bodies age, they accumulate old [senescent] cells that do not function as well as younger cells,” professor Lorna Harries, of the University of Exeter Medical School, said in a statement. “This is not just an effect of aging—it’s a reason why we age. The compounds developed at Exeter have the potential to tweak the mechanisms by which this aging of cells happens.
“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,” she added. “This research focuses on one of these mechanisms, and the findings with our compounds have potentially opened up the way for new therapeutic approaches in the future. This may well be the basis for a new generation of anti-degenerative drugs.”
In a previous study, the researchers demonstrated the ability to rejuvenate old cells in the laboratory. In the new study, they looked at precisely targeting and rejuvenating mitochondria in old cells.
Genes are all capable of making more than one product and splicing factors are the genes that make the decisions about which of the products are ultimately made.
The researchers also identified two splicing factors that play a crucial role in when and how endothelial cells—the cells that line the inside of blood vessels—become senescent. They used novel chemicals to specifically target SRSF2 or HNRNPD—two splicing factors that play a key role in determining how and why cells change with advancing age.
“Nearly half of the aged cells we tested showed signs of rejuvenating into young cell models,” Harries said.
The team tested three different compounds—AP39, AP123 and RT01—developed in the lab, each of which produced a 40-to-50 percent reduction in the amount of senescent blood vessel cells. The three compounds were specifically designed to selectively deliver minute quantities of hydrogen sulfide gas to the mitochondria in cells and help old or damaged cells generate the energy required for survival and to reduce senescence.
“Our compounds provide mitochondria in cells with an alternative fuel to help them function properly,” professor Matt Whiteman, also from the University of Exeter, said in a statement. “Many disease states can essentially be viewed as accelerated aging, and keeping mitochondria healthy helps either prevent or, in many cases using animal models, reverse this. Our current study shows that splicing factors play a key role in determining how our compounds work.”
The study was published in Aging.
