Scripps Florida Scientists Identify Compounds That Significantly Increase Healthy Aging
Aging happens to everyone, but it may no longer mean a descent into disease or chronic disability. Recently, scientists from the Florida campus of The Scripps Research Institute (TSRI) identified a class of compounds, using animal models and human cells, that significantly delays the onset of several age-related symptoms and extends healthy aging—what has come to be known as “healthspan.”
The study, published in the journal Nature Communications, was led by TSRI Professor Paul Robbins and Associate Professor Laura Niedernhofer.
This newly identified class of drugs targets senescent cells—cells that have stopped replicating because of chromosome damage. As we get older, senescent cells accumulate, becoming a major contributor to age-related diseases.
Robbins and his colleagues developed a new screening platform to look for drugs that specifically affect senescent cells. They identified a class of compounds that inhibits a stabilizing protein as having significant anti-senescent activity.
“Our study documents that you can identify compounds that kill these damaged cells specifically,” Robbins added. “It also proves that this class of drugs can significantly extend healthspan.”
Animal models treated with one of these inhibitors reduced or delayed onset of multiple age-related symptoms, including osteoporosis and frailty, which led to a major improvement in overall healthspan.
The inhibitors blocked the activity of a protein that plays a key role in survival of senescent cells, which led to their apoptosis or programmed cell death.
Although these inhibitors have anti-senescent activity in cell culture and in animal models, it is likely that they will be more effective in combination with other FDA-approved drugs that target other senescent cell pathways. More effective drug combinations, including ones with these inhibitors, could be used to extend healthspan in humans, according to the scientists.
“Our screening platform already has identified multiple classes of compounds that extend healthspan in animal models,” Robbins said. “Right now, we have a pipeline of compounds that should be even more effective than the ones in the study.”
Anti-senescent drugs may also prove useful in delaying, preventing, or treating age-related chronic diseases, as well as other disorders related to increased senescent cell accumulation, such as obesity with metabolic syndrome and osteoarthritis. Cancer survivors treated with irradiation or chemotherapy could also benefit.
“We found that there are at least two main groups of drugs that work as anti-senescent therapeutics: one that suppresses the senescent state, termed senomorphics, and one that kills senescent cells, termed senolytics,” said Heike Fuhrmann-Stroissnigg, the first author of the study. “So far, most of the drugs identified belong to this latter group—and some of these drugs are used as anti-cancer drugs too.”
In addition to Robbins, Niedernhofer and Fuhrmann-Stroissnigg, other authors of the study, “Identification of HSP90 Inhibitors as a Novel Class of Senolytics,” are Yuan Yuan Ling, Jing Zhao, Sara J. McGowan, Robert W. Brooks, Akaitz Dorronsoro, Lana Corbo, Priscilla Tang, Christina Bukata, Diego Grassi and Xuesen Li of TSRI; Siobhan Q. Gregg and Jennifer L. Stripay of the University of Pittsburgh School of Medicine; Yi Zhu, Tamara Tchkonia and James L. Kirkland of the Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota; and Nadja Ring and Mauro Giacca of the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
The study was supported by the National Institutes of Health (grant numbers AG043376, AG13925, DK50456), the Connor Group; the Noaber, Ted Nash, and Glenn Foundations; the American Federation for Aging Research; and Aldabra Biosciences.
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