A graduate student’s wild idea leads to a major breakthrough in the field of aging
One potential strategy for treating a wide range of diseases involves targeting senescent cells. These cells – also known as “zombie cells” – stop multiplying but fail to remove 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, the main challenge is detecting them within living tissue without disturbing nearby healthy cells.
Researchers at Mayo Clinic, write in the journal senescent celldescribed a new method for labeling senescent cells. Their approach uses “aptamers” – short pieces of synthetic DNA that can fold to form three-dimensional structures. These structures can bind 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 cells,” says biochemist and molecular biologist Jim Maher, III, Ph.D., the study’s lead author. “Although this study is a first step, the results suggest that this 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 a strange idea during an informal discussion with a colleague.
Keenan Pearson, PhD – who recently received his degree from the Mayo Clinic Graduate School of Biomedical Sciences – has been working with Dr. Maher on how aptamers could be used in neurodegenerative diseases or brain cancer.
Meanwhile, several floors above, fellow graduate student Sarah Jachem, Ph.D., was studying senescent cells and aging in the lab of researcher Nathan LePraseur, Ph.D.
Their paths crossed at a scientific meeting, where they exchanged ideas for their thesis projects. Dr. Pearson wondered whether aptamers could be adapted to detect senescent cells. “I thought the idea was good, but I didn’t know about the process of preparing senescent cells to test them, so that was a nice experience,” says Dr. Pearson, who became the lead author of the publication.
Mentors support the student’s bold idea
The students brought their concept to their advisors and to researcher Darren Baker, Ph.D., whose work focuses on senescent cell therapies. Dr. Maher recalls that the idea initially struck him as “crazy” but worth exploring. The three mentors supported the proposal. “We honestly loved that it was the students’ idea and a real synergy between two research areas,” says Dr. Maher.
As early experiments produced promising results, the duo recruited more students from their labs. Then-graduate students Brandon Wilbanks, Ph.D., Luis Brito, Ph.D., and M.D. Student Caroline Doherty added new techniques, including advanced microscopy and additional tissue types. “It became encouraging to put in more effort, because we could tell it was a project that would succeed,” says Dr. Yachim.
Uncovering new evidence about senescent cells
In addition to providing a labeling method, the research provided insight into the biology of senescent cells. “Until now, there are no universal markers that distinguish senescent cells,” says Dr. Maher. “Our study was set up to be open about which surface molecules to target on senescent cells. The beauty of this approach is that we allow the aptamers to choose which molecules to bind to.”
The team found that many of the aptamers bound to a different type of protein called fibronectin on the surface of mouse cells. Scientists don’t yet know how this fibronectin variant is linked to aging. However, his discovery suggests that aptamers may help define the unique features of 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 therapy directly to these cells. Dr. Pearson points out that aptamers are less expensive and more flexible than traditional antibodies, which are typically used to distinguish one cell type from another.
“This project demonstrated a new concept,” says Dr. Maher. “Future studies may expand the approach to include applications related to senescent cells in human diseases.”
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