Scientists have successfully reversed the process of aging in cells for the first time in a move which could help beat the likes of Alzheimer’s, dementia, increased longevity, and possibly be the first step toward eternal physical youth.
Many people hope to reverse the process of ageing in a bid to remain healthier and live longer or ultimately to live forever.
And now scientists have made a groundbreaking breakthrough in this research.
As the body ages, it loses its ability to control how genes are regulated and they ultimately become more damaged until we ultimately die.
A gene is activated by signals from inside or outside the cell to make a molecular message known as RNA.
The decision on which type of ‘message’ is created by a group of around 300 proteins is known as “splicing factors”.
However, as we get older the amount of splicing factors the proteins are able to make steadily decreases.
Older cells are then ultimately less able to turn genes on and off to react to the environment which makes us more vulnerable to diseases which ultimately kill us off.
However, researchers have found a way to turn splicing factors back on.
Scientists Lorna Harries, Associate Professor in Molecular Genetics and Matt Whiteman, Professor of Experimental Therapeutics, both at University of Exeter, write for the Conversation:
“In our new work, we showed that by treating old cells with a chemical that releases small amounts of hydrogen sulphide, we were able to increase levels of some splicing factors, and to rejuvenate old human cells.
“Hydrogen sulphide is a molecule that is found naturally in our bodies and has been shown to improve several features of age-related disease in animals.
“But it can be toxic in large amounts, so we needed to find a way to deliver it directly to the part of the cell where it is needed.
“By using a ‘molecular postcode’ we have been able to deliver the molecule directly to the mitochondria, the structures that produce energy in cells, where we think it acts, allowing us to use tiny doses, which are less likely to cause side effects.”
According to the abstract, Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2.
Cellular senescence is a key driver of ageing, influenced by age-related changes to the regulation of alternative splicing. Hydrogen sulfide (H2S) has similarly been described to influence senescence, but the pathways by which it accomplishes this are unclear.
We assessed the effects of the slow release H2S donor Na-GYY4137 (100 µg/ml), and three novel mitochondria-targeted H2S donors AP39, AP123 and RT01 (10 ng/ml) on splicing factor expression, cell proliferation, apoptosis, DNA replication, DNA damage, telomere length and senescence-related secretory complex (SASP) expression in senescent primary human endothelial cells.
All H2S donors produced up to a 50% drop in senescent cell load assessed at the biochemical and molecular level. Some changes were noted in the composition of senescence-related secretory complex (SASP); IL8 levels increased by 24% but proliferation was not re-established in the culture as a whole.
Telomere length, apoptotic index and the extent of DNA damage were unaffected.
Differential effects on splicing factor expression were observed depending on the intracellular targeting of the H2S donors. Na-GYY4137 produced a general 1.9 – 3.2-fold upregulation of splicing factor expression, whereas the mitochondria-targeted donors produced a specific 2.5 and 3.1-fold upregulation of SRSF2 and HNRNPD splicing factors only.
Knockdown of SRSF2 or HNRNPD genes in treated cells rendered the cells non-responsive to H2S, and increased levels of senescence by up to 25% in untreated cells.Our data suggest that SRSF2 and HNRNPD may be implicated in endothelial cell senescence, and can be targeted by exogenous H2S.
These molecules may have potential as moderators of splicing factor expression and senescence phenotypes.
James E Windsor, Overpasses News Desk
August 14th, 2018