Researchers at the Mayo Clinic have made a significant breakthrough in identifying “zombie” cells, which are associated with aging and various diseases, utilizing DNA-based molecules known as aptamers. These senescent cells, which cease to divide but do not die as normal cells do, accumulate in the body and are linked to major health conditions such as cancer and Alzheimer”s disease.
In a recent study published in the journal Aging Cell, the team developed an effective method to locate these problematic cells. The researchers employed aptamers, which are short synthetic DNA strands that can naturally fold into intricate three-dimensional structures. These molecules can bind to specific proteins found on the surface of cells, enabling scientists to differentiate between various cell types.
During experiments with mouse cells, the researchers identified several unique aptamers selected from an extensive pool of over 100 trillion DNA sequences. These aptamers successfully attached to proteins that are specific to senescent cells, thereby tagging them for easier detection. “This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones,” stated Jim Maher, III, Ph.D., a biochemist and molecular biologist who led the study. “Though this study is a first step, the results suggest the approach could eventually apply to human cells.”
The origin of this project stems from a conversation between graduate students at Mayo Clinic. Keenan Pearson, Ph.D., who recently graduated from the Mayo Clinic Graduate School of Biomedical Sciences, was investigating how aptamers could be utilized in the context of neurodegenerative diseases and brain cancer. Meanwhile, Sarah Jachim, Ph.D., was working under researcher Nathan LeBrasseur, Ph.D., on senescent cells and aging. They discussed the potential of aptamer technology to identify senescent cells during a scientific event.
After presenting the idea to their mentors, the students received encouragement despite initial skepticism about the concept. Their mentors were eager to support the synergy of the two research areas. The students quickly obtained promising results, prompting them to involve additional peers from their respective labs, including graduate students Brandon Wilbanks, Ph.D., Luis Prieto, Ph.D., and M.D.-Ph.D. student Caroline Doherty, who contributed various methodologies and tissue samples.
Beyond merely identifying senescent cells, the study has shed light on their characteristics. “To date, there aren”t universal markers that characterize senescent cells,” noted Maher. “Our study was set up to be open-ended regarding 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 researchers discovered that some aptamers bound to a variant of the protein fibronectin found on the surface of mouse cells. The exact role of this fibronectin variant in the context of senescence remains to be understood. This finding indicates that aptamers could serve as a valuable tool for defining the unique characteristics of senescent cells. Future research will aim to identify aptamers capable of detecting senescent cells in humans.
Aptamers offer a cost-effective and versatile alternative to traditional antibodies that are typically used to differentiate cell types. “This project demonstrated a novel concept,” concluded Maher. “Future studies may extend the approach to applications related to senescent cells in human disease.”
