Researchers at the Systems Biology Institute at Yale’s West Campus have developed a new efficient and cost-effective drug screening technique, using the tool, the researchers have discovered two novel compounds with lifespan-extending properties.
The new technique, termed High Life, can be used to compare more than 1,000 compounds per day for their effects on lifespan — hundreds of times more than the five to 10 compounds scientists could test daily in the past. This approach, detailed in a study published in the journal Cell Reports on Nov. 28, offers researchers the opportunity to advance research into human aging and promote therapeutic discoveries that will improve the health of the elderly, according to Murat Acar, a molecular, cellular and developmental biology and physics professor and the senior author of the study.
“The ultimate long-term goal of our lab’s research is to contribute to the field that helps reverse the aging process and keep people living longer, healthier lives,” said lead author Ethan Sarnoski GRD ’19. “In this particular project, we jump-started the early stages of that process through preclinical drug discovery.”
Research in the field of aging is essential today, Acar said, as people are living longer and longer. He noted that aging has become the primary risk factor for contracting diseases or dying in the developed world. Therefore, understanding the process of aging and developing methods to enhance health outcomes during this process — by identifying new drug candidates, for example — has become a goal for many researchers.
High-Life analyses how different compounds affect lifespan by using fluorescence to differentiate live and dead cells and to determine number of cell divisions. According to Sarnoski, the technique offers two key benefits. First, it dramatically increases the rate at which researchers can progress by enabling the screening of more than a thousand compounds a day.
The second advantage is that the technique reduces the cost of experiments. The cost to test one drug condition using High Life is 50 to 60 cents, while that of traditional methods can range from $10 to a couple hundred dollars, Sarnoski said.
After they developed the technique, the researchers used High Life to screen a total of 2,640 compounds, which included both Food and Drug Administration–approved compounds, as well as compounds that had failed clinical development.
From this analysis, they found two compounds that did extend the lifespan of yeast, performing additional cellular testing after screening to confirm the results. The two compounds, terreic acid and mycophenolic acid, extended average lifespan by 15 and 20 percent, respectively, according to the study.
According to Acar, the team’s findings in the yeast model may be relevant to humans because distantly related model organisms share many aging mechanisms. He added that the yeast species was chosen because of its relatively short lifespan. With a mother cell dividing every 90 minutes, he said, baker’s yeast provides the fastest model for eukaryotic lifespan.
In order to further investigate the two compounds’ effects on lifespan, the researchers are currently testing the two compounds in other model organisms — including ones that are more similar to humans — Sarnoski said.
The researchers are also performing studies to characterize their mechanisms and using High Life to screen an additional 18,000 compounds to look for more drug candidates that could play a role in extending lifespan.
The Population Reference Bureau projects that the number of elderly Americans aged 65 and older will increase to over 98 million by 2060, from 46 million in 2016.
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