Treatments for aging and cancer could be improved thanks to new senescence research.
Senescence is a key process whereby cells stop proliferating. It protects us against cancer, but at the cost of promoting aging, as well as diseases such as diabetes and atherosclerosis.
While most research into senescence has focussed on fibroblasts, new research has turned the spotlight on epithelial cells, where most cancers arise. This led the research team, from the University of Southern California’s Viterbi School of Engineering (CA, USA), to results with the potential to provide new treatments for aging and cancer.
The group forced a halt to production of nucleotides in ‘young’ cells, which led them to become senescent. Metabolomics and 3D imagery revealed that senescent cells could not synthesize DNA, and often had two nuclei. Telomerase expression reversed their observations.
“This means that the production of nucleotides is essential to keep cells young,” explained Alireza Delfarah, first author of the study. “It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly.”
The research has implications for the design of new drugs in the field of senolytics – that is, the development of drugs able to eliminate aging cells. Senolytics trials are at an early stage, having thus far shown that elimination of senescent cells in mice results in better aging and a more productive life span.
"This means that the production of nucleotides is essential to keep cells young"
“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,” noted Nick Graham, group leader.
He pointed out that the goal should not be to stop senescence completely, as that could put us at risk for cancer. Senolytics therefore need to target senescent cells without allowing cancer cells to overcome this natural barrier.
A clearer understanding of the process is therefore important. “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 concluded.
Written By Francesca Lake
Source Delfarah A, Parrish S, Junge JA et al. Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells. J. Biol. Chem. 294(27), 10564–10578 (2019); http://www.jbc.org/content/294/27/10564.long https://viterbischool.usc.edu/news/2019/07/fighting-back-against-the-ravages-of-time/