Self-assembling senolytics precisely target and eliminate senescent cells while leaving healthy cells unharmed.
A research team at Ulsan National Institute of Science and Technology (UNIST) has achieved a significant breakthrough in the treatment of age-related diseases with a promising new approach that selectively removes senescent cells, without harming normal healthy cells. This interesting development could usher in a new era of targeted therapeutic interventions.
Longevity.Technology: Aging cells, known as senescent cells, contribute to various inflammatory conditions and age-related ailments as humans age. Senolytics, which eliminate senescent cells from tissues, represent an emerging therapeutic strategy for various age-related diseases – but it is a strategy that is not without risk. Many senolytics target antiapoptotic proteins because they are overexpressed in senescent cells, but they are still expressed in other cells, meaning this approach lacks specificity and can result in cell death for normal cells and severe side effects for the user.
To address this issue, the UNIST research team focused on developing tech that could precisely target and eliminate senescent cells, while sparing normal healthy cells, coming up with neat self-assembling senolytics that can targeting aging cells with an intracellular oligomerization system.
In their study, the research team led by Professor Ja Hyoung Ryu from the Department of Chemistry at UNIST, in collaboration with Professor Hyewon Chung from Konkuk University, designed organic molecules that selectively target receptors overexpressed in the membranes of aging cells. By leveraging the higher levels of reactive oxygen species (ROS) found in aging cells, these molecules promote the formation of disulfide bonds and create oligomers that bind together [1].
Through self-assembly of these oligomers, the researchers successfully created artificial proteins with a stable α-helix secondary structure. These protein-like nanoassemblies exhibited strong binding affinity to the mitochondrial membranes of aging cells, leading to membrane disruption and subsequent cell self-destruction.
“The selective removal of aging cells by targeting the mitochondria and inducing dysfunction has been successfully demonstrated in our experiments,” stated Professor Ryu. “This approach represents a new paradigm for treating age-related diseases [2].”
This innovative technology offers several advantages, including minimal toxicity concerns and a wide therapeutic window by specifically targeting organelles within cells. It opens up exciting possibilities for designing preclinical and clinical trials in the future.
[1] https://pubs.acs.org/doi/10.1021/jacs.3c06898
[2] https://tinyurl.com/5xv7zw5b
