One potential strategy for treating a wide range of illnesses involves targeting senescent cells. These cells — also known as “zombie cells” — stop multiplying but fail to clear themselves from the body as healthy cells normally do. They appear in many conditions, including cancer, Alzheimer’s disease, and throughout the aging process. Although scientists are working on ways to eliminate or repair these cells, a major challenge has been detecting them within living tissue without disturbing nearby healthy cells.
Researchers at Mayo Clinic, writing in the journal Aging Cell, describe a new method for labeling senescent cells. Their approach uses “aptamers” — short pieces of synthetic DNA that fold into three-dimensional structures. These structures can attach to proteins found on the outer surfaces of cells. In experiments with mouse cells, the team identified several rare aptamers, selected from more than 100 trillion random DNA sequences, that were able to recognize specific surface proteins and mark senescent cells.
“This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones,” says biochemist and molecular biologist Jim Maher, III, Ph.D., a principal investigator of the study. “Though this study is a first step, the results suggest the approach could eventually apply to human cells.”
How a Chance Conversation Sparked a Collaboration
The idea that led to this project began when a Mayo Clinic graduate student shared an offbeat thought during a casual discussion with a classmate.
Keenan Pearson, Ph.D. — who recently received his degree from Mayo Clinic Graduate School of Biomedical Sciences — had been working with Dr. Maher on how aptamers might be used for neurodegenerative diseases or brain cancer.
Meanwhile, several floors above, fellow graduate student Sarah Jachim, Ph.D., was studying senescent cells and aging in the lab of researcher Nathan LeBrasseur, Ph.D.
Their paths crossed at a scientific gathering, where they exchanged ideas about their thesis projects. Dr. Pearson wondered if aptamers could be adapted to detect senescent cells. “I thought the idea was a good one, but I didn’t know about the process of preparing senescent cells to test them, and that was Sarah’s expertise,” says Dr. Pearson, who became lead author of the publication.
Mentors Back a Bold Student Idea
The students brought their concept to their advisors and to researcher Darren Baker, Ph.D., whose work centers on senescent cell therapies. Dr. Maher recalls that the idea initially struck him as “crazy” but worth exploring. All three mentors supported the proposal. “We frankly loved that it was the students’ idea and a real synergy of two research areas,” says Dr. Maher.
As early experiments produced promising results, the pair enlisted more students from their labs. Then-graduate students Brandon Wilbanks, Ph.D., Luis Prieto, Ph.D., and M.D.-Ph.D. student Caroline Doherty added new techniques, including advanced microscopy and additional tissue types. “It became encouraging to expend more effort,” Dr. Jachim says, “because we could tell it was a project that was going to succeed.”
Revealing New Clues About Senescent Cells
Beyond providing a tagging method, the research offered insight into the biology of senescent cells. “To date, there aren’t universal markers that characterize senescent cells,” says Dr. Maher. “Our study was set up to be open-ended about the target surface molecules on senescent cells. The beauty of this approach is that we let the aptamers choose the molecules to bind to.”
The team found that several aptamers attached to a variant of a protein called fibronectin on the surface of mouse cells. Scientists do not yet know how this fibronectin variant relates to senescence. However, its discovery suggests that aptamers may help identify features unique to senescent cells.
Potential Applications for Human Health
More work will be needed to find aptamers that can reliably detect senescent cells in human tissue. If aptamers can be adapted for this purpose, they could eventually be used to deliver treatments directly to these cells. Dr. Pearson notes that aptamers are less costly and more flexible than traditional antibodies, which are commonly used to distinguish one cell type from another.
“This project demonstrated a novel concept,” says Dr. Maher. “Future studies may extend the approach to applications related to senescent cells in human disease.”