“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. 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,” said Assistant Professor Nick Graham.
Senescence is a natural process in which cells permanently stop creating new cells, this process can be a double edged sword, and is one of the key causes of age related decline manifesting in diseases including heart disease and arthritis.
“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,” says lead author Alireza Delfarah.
Senescent cells were discovered to stop producing nucleotides which are the building blocks of DNA; when young cells were forced to stop producing nucleotides they became senescent. “This means that the production of nucleotides is essential to keep cells young,” Delfarah said. “It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly.”
Young cells proliferating robustly were fed molecules labeled with isotopes of carbon to enable tracing of how the nutrients consumed by a cell were processed into different biochemical pathways. 3D imaging unexpectedly revealed that senescent cells often have 2 nuclei, and that they do not synthesize DNA.
Rather than focussing on fibroblasts the feam focussed on how senescence occurs in epithelial cells lining the surfaces of organs and structures in the body, which are also the type of cells in which most cancers arise.
Senescence is the body’s protective barrier against cancer; when cells sustain damage that could be them at risk for cancer they enter senescence and stop proliferating as to not develop into cancer and spread.
“Sometimes people talk about senescence as a double-edged sword, that it protects against cancer, and that’s a good thing,” Graham said. “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.”
“They can take a mouse that’s aging and diminishing in function, treat it with senolytic drugs to eliminate the senescent cells, and the mouse is rejuvenated. If anything, it’s these senolytic drugs that are the fountain of youth.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,” Graham said.
