Researchers from the biotechnology company Integrated Biosciences have published a new study in the May issue of Nature Aging showcasing the potential of artificial intelligence (AI) to identify new senolytic compounds. These compounds are a group of small molecules that are being researched for their ability to hinder age-related processes like cancer, inflammation, and fibrosis.
The new research paper titled “Discovering small-molecule senolytics with deep neural networks” outlines a study conducted by researchers from MIT and the Broad Institute of MIT and Harvard, which used AI to screen over 800,000 compounds. The study identified three drug candidates that showed superior medicinal chemistry properties than currently investigated senolytics, with comparable efficacy.
“This research result is a significant milestone for both longevity research and the application of artificial intelligence to drug discovery,” said Felix Wong, Ph.D., co-founder of Integrated Biosciences and first author of the publication. “These data demonstrate that we can explore chemical space in silico and emerge with multiple candidate anti-aging compounds that are more likely to succeed in the clinic, compared to even the most promising examples of their kind being studied today.”
Senolytics is a class of drugs that target senescent cells, which are cells that have stopped dividing and are no longer useful in the body. These compounds work by triggering senescent cells to self-destruct, allowing healthy cells to replace them and heal any damage they have caused. The idea of senolytics is that by removing senescent cells, the body is better equipped to prevent age-related diseases and extend healthy aging.
Although there have been promising clinical results, the senolytic compounds discovered so far have been limited by unfavorable bioavailability and negative side effects. Integrated Biosciences uses next-generation tools such as AI and synthetic biology to advance anti-aging drug development and target neglected hallmarks of aging. The company was founded in 2022 with the aim of overcoming these obstacles.
“One of the most promising routes to treat age-related diseases is to identify therapeutic interventions that selectively remove these cells from the body similarly to how antibiotics kill bacteria without harming host cells. The compounds we discovered display high selectivity, as well as the favorable medicinal chemistry properties needed to yield a successful drug,” said the publication’s joint first author, Dr. Satotaka Omori, who serves as the Head of Aging Biology at Integrated Biosciences. “We believe that the compounds discovered using our platform will have improved prospects in clinical trials and will eventually help restore health to aging individuals.”
As previously mentioned, from a pool of more than 800,000 molecules, three compounds were chosen based on their structural and biochemical characteristics, and were found to bind with Bcl-2. This protein is responsible for controlling cell death and is targeted by chemotherapy. One of these compounds was tested on mice that were about 80 weeks old, equivalent to 80-year-old humans, and was found to eliminate senescent cells and decrease the expression of genes associated with senescence in the kidneys.
According to James J. Collins, Ph.D., Termeer Professor of Medical Engineering and Science at MIT and founding chair of the Integrated Biosciences Scientific Advisory Board, this work showcases the potential of AI to develop treatments that combat aging – a major biological challenge in medicine.
Reference: Phys.org
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