As medical technology continues to advance, some scientists are hoping they can find a way to combat aging itself. A step towards that goal may have just been made, as a recently published paper explains how researchers at the University of Exeter have managed to reverse aging in certain human cells.
Senescent Cells – The Cause Of Aging?
One hypothesis is that aging is related to the build up of certain cell types in the body. “Senescent cells” are cells which have grown old and not just deteriorated themselves, but are preventing other cells in the body from properly carrying out their functions. Animal studies have found that isolating and removing the senescent cells can combat some of the known effects of aging, such as inhibiting the development of cataracts.
There are competing theories on how senescent cells develop, with some theories postulating that damage to the telomeres of chromosomes (protective molecules located on the end of chromosomes) or other damage to the DNA can contribute to their development.
While senescent cells aren’t capable of replicating any longer, they still stay active metabolically and frequently release pro-inflammatory secretions. Some organisms don’t have senescent cells, such as lobsters, corals, and sponges and some scientists are looking at these species for clues on how to combat aging. Some researchers hypothesize that senescent cells evolved as a means to combat the development of cancer.
Another theory behind the development of senescent cells is that they arise as a result of the body’s inability to turn genes off or on at the correct place and time. As the body ages it tends to lose its ability to regulate the expression of genes. Every cell in the body has the entire collection of DNA, genes are just switched on or off with regards to the needs of the cell. Liver cells and heart cells contain all the same genes, yet perform different functions for this reason.
How One Gene Makes Many Messages
When a gene receives an activation message, it creates RNA (Ribonucleic Acid), which contains the information needed to create the correct proteins or whatever else the cell needs. Approximately 95% of the genes in the human body can create different messages and products depending on the cell’s needs. The message each gene creates is decided by around 300 proteins dubbed splicing factors. The number of splicing factors that the body’s cells are able to make drops off as we age, so the aging cells can’t control the how genes are expressed as easily. Studies have found that levels of splicing factors decline in both human senescent cells and in blood samples taken from elderly people. The researchers identified two different splicing factors that played a critical role in how endothelial cells became senescent. These two splicing factors are SRSF2 or HNRNPD.
The researchers found that by applying a chemical that releases tiny amounts of hydrogen sulphide to the old cells, they could reverse some of the aging by increasing levels of splicing factors. Hydrogen sulphide is found within the human body naturally, and animal tests have found that the chemical improves different aspects of aging-related diseases.
However, hydrogen sulphide can also be dangerous in high amounts, as beyond a certain threshold it is toxic to cells. This means that the hydrogen sulphide must be delivered directly to the part of the cell that needs it, to avoid interfering with other parts of the cell. The researchers were able to use a “molecular postcode” to make sure the hydrogen sulphide was sent right to the cell’s mitochondria. The researchers believe that the hydrogen sulphide acts primarily in the mitochondria, so they were able to use only trace amounts of the hydrogen sulphide that are substantially less likely to create side effects. There were three different compounds the exeter team developed: RT01, AP39, AP123. The compounds assist the damaged or old cells in generating the energy needed to survive, which reduces senescence.
Hydrogen Sulphide’s Effect On Endothelial Cells
The study researched the effects of hydrogen sulphide on endothelial cells. The endothelial cells are the cells that line the inside of the blood vessels, and the researchers tried to get the hydrogen sulphide delivered to the mitochondria within them. The number of senescent cells in the entire collection of endothelial cells was reduced by around 50% when the hydrogen sulphide was applied.
The results of the study suggest that future treatments could potentially rejuvenate aging blood vessels. Blood vessels tends to become stiffer as one ages, which increases the probability that strokes or heart attack might occur. The treatment could potentially be applied to other cells as well.
Professor Lorna Harries, of the University of Exeter Medical School, says that the accumulation of senescent cells isn’t just an effect of aging, it’s the actual reason that people age. Harries explains that the compound the Exeter scientists developed could potentially tweak the processes that lead to the aging of cells. Harries explains how one or two mechanisms seem to be responsible for aging:
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 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.
Harries says many states of disease can basically be considered accelerated aging and that assisting the mitochondria in their functioning would help prevent or treat the disease. The goal is to help people not merely live longer, but to live longer with a better quality of life, free of diseases brought about by cell senescence. Though that treatment is still sometime in the future, the current research is a promising first step to such treatment.
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