New software finds aging cells that contribute to disease and health risks

(Press-News.org) For human health, prematurely aging cells are a big problem. When a cell ages and stops growing, its function changes, which can cause or worsen cardiovascular disease, Alzheimer’s disease and other chronic diseases. But these cells are also like needles in a haystack, difficult to identify by traditional scientific measures. 

To find these problematic cells, a University of Illinois Chicago doctoral student has developed a powerful new software platform called SenePy. In a paper for Nature Communications, Mark Sanborn and co-authors from the College of Medicine announced the open-source tool to find aging — or senescent — cells in organs and tissues. 

The tool will give researchers a boost for studying these biologically important cells to better understand and treat several diseases, according to the paper’s lead author, Dr. Jalees Rehman, Benjamin J. Goldberg Professor and head of the department of biochemistry and molecular genetics. 

“Cellular senescence describes the premature aging of a cell where the cell stops growing, doesn’t die, but it stops functioning normally,” said Rehman, who is also a member of the University of Illinois Cancer Center. “That causes problems because the cell is not replaced by healthy cells. Instead, it persists and promotes inflammation, thus disrupting the function of its neighboring cells.” 

To develop SenePy, Sanborn analyzed single-cell sequencing data from over 1.6 million human and mouse cells. On this large dataset, he used computational tools to find genetic signatures that distinguish aging cells from their healthier neighbors. 

But it wasn’t as simple as finding one set of common markers for senescent cells everywhere in the body. In different tissues, such as the heart, lungs or brain, the genetic profile of aging cells also differs, the researchers found. In all, they identified 72 mouse and 64 human signatures. 

SenePy helps make sense of that complexity, allowing researchers to analyze their own tissue samples and compare them to the database of signatures the UIC team discovered. The code for the platform is open-source and free to use. 

“More people will use it and find value in it because, as an open-source tool, it is freely available to the scientific community,” said Sanborn, a doctoral student in the Graduate Education in Biomedical Sciences program. “If there’s more people using it, then there’s more potential for it to have a future therapeutic impact.” 

In the Nature Communications paper, the researchers used SenePy to examine the role of senescent cells in cancer, heart attacks, COVID-19 and brain inflammation.  

“We found that senescent cells are clustered together, because premature senescence in one cell promotes dysfunction and senescence in its neighbors,” Rehman said. “SenePy also allowed us to study how senescence acts as a natural brake which prevents tumor formation. High levels of activation of a cancer-promoting gene in cells also resulted in higher SenePy senescence scores.” 

The team also looked at the effectiveness of drugs called senolytics that clear senescent cells from the body to fight or prevent disease and aging. 

“Because we now have several markers for specific types of senescence and different cell types, we could generate new senolytics for potential new targets,” Sanborn said. 

Additional UIC co-authors include Xinge Wang, Shang Gao and Yang Dai. The research was funded by grants from the National Institutes of Health. 

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