“To drink from the fountain of youth, you have to figure out where the fountain of youth is and understand what the fountain of youth is doing,” says Nick Graham, who adds, “We’re doing the opposite; we’re trying to study the reasons cells age so that we might be able to design treatments for better aging.”
Their team recently published a study in the Journal of Biological Chemistry of an in depth investigation at what happens to cells going through senescence.
“Senescent cells are effectively the opposite of stem cells, which have an unlimited potential for self-renewal or division. Senescent cells can never divide again. It’s an irreversible state of cell cycle arrest,” explains the study’s lead author, USC doctoral student Alireza Delfarah.
Senescence has been shown to be a part of age related decline, most research focuses on the process in fibroblasts, but this study chose to analyze the process in epithelial cells which are present in the tissues at the surface of organs and other body tissues; these are also the type of cells in which most forms of cancer begin.
Young epithelial cells were fed chemically labeled molecules to see how the cells processed nutrients; as the cells reached senescence they were observed to stop producing nucleotides, which are organic molecules that are the main components of DNA.
Artificially halting young cell nucleotide production was found to immediately lead to the cells entering the stage of senescence, meaning production of nucleotides is essential to keeping cells young, and by preventing cells from losing nucleotide synthesis cells may age more slowly.
3D images of the senescent cells were developed which revealed that these cells had two nuclei cellular centers that were unable to synthesize DNA.
Findings may help to develop ways to stop senescence, however it may be difficult as the process is also a protective mechanism to prevent cancer for developing along with contributing to age related decline. These findings may contribute to the development of senolytics drugs that could help to remove aging cells and promote healthier living into older ages.
“Sometimes people talk about senescence as a double-edged sword; that it protects against cancer, and that’s a good thing. But then it also promotes aging and diseases like diabetes, cardiac dysfunction or atherosclerosis, and general tissue dysfunction. We would like to find a way to remove senescent cells to promote healthy aging and better function,” says Graham.
“Researchers can take a mouse that’s aging and diminishing in function and give it these senolytic drugs to eliminate the senescent cells, and the mouse is rejuvenated. So if anything, it’s these senolytic drugs that are the fountain of youth,” says Graham.
“That’s where we’re coming in—studying senescent cell metabolism and trying to figure out how the senescent cells are unique so that you could design targeted therapeutics around these metabolic pathways.”
