Mayo Clinic researchers using DNA aptamers to tag glowing senescent 'zombie' cells in mouse tissue under microscope.
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Mayo Clinic team uses DNA aptamers to tag senescent ‘zombie’ cells

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Researchers at Mayo Clinic have developed an aptamer-based technique to tag senescent, or so‑called “zombie,” cells in living mouse tissues, work they say could eventually support targeted therapies for age‑related diseases. The project grew out of a chance conversation between two graduate students, according to Mayo Clinic.

Senescent cells are cells that permanently stop dividing in response to stress or damage but remain metabolically active. They are widely studied because they are linked to aging and a range of age‑related diseases. However, reliably detecting these cells in living tissues, while sparing healthy cells, has been a significant challenge for researchers who hope to eliminate or repair them.

In a study published in the journal Aging Cell, a Mayo Clinic team reports a new method that uses DNA aptamers—short, synthetic strands of DNA that fold into three‑dimensional shapes and bind to proteins on cell surfaces—to distinguish senescent mouse cells from non‑senescent cells.

According to Mayo Clinic, the researchers carried out cell‑culture experiments in mouse fibroblasts, screening a library of trillions of random DNA sequences to identify rare aptamers that attached selectively to senescent cells by recognizing specific surface proteins.

"This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones," said principal investigator L. James (Jim) Maher III, Ph.D., a biochemist and molecular biologist at Mayo Clinic.

As described by Mayo Clinic’s news release and related coverage, the project began with a chance conversation between two graduate students, Keenan S. Pearson, Ph.D., and Sarah K. Jachim, Ph.D. Pearson, working in Maher’s lab, had been studying how aptamers might be applied to neurodegenerative diseases or brain cancer, while Jachim, in the lab of aging researcher Nathan K. LeBrasseur, Ph.D., brought expertise in preparing senescent cells.

Pearson suggested adapting aptamer technology to target senescent cells, and Jachim’s experience with senescence models helped make the idea feasible, according to Mayo Clinic. The students brought the concept to their mentors, including Darren J. Baker, Ph.D., who studies senescent cell biology and therapies, leading to a broader collaboration.

Additional contributors to the Aging Cell paper included graduate students Brandon A. Wilbanks, Ph.D., and Luis I. Prieto, Ph.D., and M.D.–Ph.D. student Caroline D. Doherty, who helped apply advanced microscopy and examine additional mouse tissues. The team reports that several of the selected aptamers bind to a variant form of fibronectin, a protein found on the surface of mouse senescent cells. The exact role of this fibronectin variant in senescence is not yet understood, but it may represent a new biological marker of senescent cells.

While the current work was conducted in mouse cells and tissues, Mayo Clinic notes that aptamers could, in principle, be adapted for use in human samples. The researchers say more studies will be needed to identify aptamers that reliably recognize human senescent cells and to test whether such molecules could be used to deliver therapies directly to those cells.

Pearson also points out that aptamer technology can be less expensive and more versatile than traditional antibodies, which are typically used to distinguish different cell types.

"This project demonstrated a novel concept," Maher said. "Future studies may extend the approach to applications related to senescent cells in human disease."

According to Mayo Clinic, Pearson is the lead author of the study, titled "An Unbiased Cell-Culture Selection Yields DNA Aptamers as Novel Senescent Cell-Specific Reagents," published online in Aging Cell in 2025.

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