Integrated Biosciences, a biotechnology company combining synthetic biology and machine learning to target aging, in collaboration with researchers at the Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, today announced results demonstrating the power of artificial intelligence (AI) to discover novel senolytic compounds, a class of small molecules under intense study for their ability to suppress age-related processes such as fibrosis, inflammation and cancer. A new publication authored by company founders in Nature Aging, “Discovering small-molecule senolytics with deep neural networks,” describes the AI-guided screening of more than 800,000 compounds to reveal three drug candidates with comparable efficacy and superior medicinal chemistry properties than those of senolytics currently under investigation.

Senolytics are an emerging class of investigational drug compounds that selectively kill aging-associated senescent cells (left, with red stain) without affecting other cells (right). Using artificial intelligence, researchers from Integrated Biosciences have, for the first time, identified three senolytics with comparable efficacy and superior drug-like properties relative to leading investigational compounds. 

“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 are compounds that selectively induce apoptosis, or programmed cell death, in senescent cells that are no longer dividing. A hallmark of aging, senescent cells have been implicated in a broad spectrum of age-related diseases and conditions including cancer, diabetes, cardiovascular disease, and Alzheimer’s disease. Despite promising clinical results, most senolytic compounds identified to date have been hampered by poor bioavailability and adverse side effects. Integrated Biosciences was founded in 2022 to overcome these obstacles, target other neglected hallmarks of aging, and advance anti-aging drug development more generally using artificial intelligence, synthetic biology and other next-generation tools.

“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 Satotaka Omori, Ph.D., Head of Aging Biology at Integrated Biosciences and joint first author of the publication. “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.”

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Combining technologies that proved hugely successful against cancer and in COVID-19 vaccines, researchers at the University of Pennsylvania have shown they can effectively treat a leading cause of heart disease. For now the success has only been achieved in mice, but the milestone offers hope for millions of people whose heart muscle is damaged by scar tissue. There is no effective treatment for this fibrosis, which leads to heart disease, the leading cause of death in the United States, said Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published in the journal Science.

In his new research, Epstein reversed fibrosis by re-engineering cells, as has been done with a successful blood cancer treatment called CAR-T. In this case, however, the treatment took place inside the body rather than in a lab dish. The team delivered the treatment using mRNA technology, which has been proven over the last year with hundreds of millions of people receiving mRNA-based COVID vaccines.

“If it works (in people), it really could have enormous impact,” Epstein said. “Almost every type of heart disease is accompanied by fibrosis.”

About 50% of heart failure is directly caused by this scar tissue, which prevents the heart from relaxing and pumping effectively. Fibrosis also is involved in leading causes of lung and kidney disease.

Source: https://eu.usatoday.com