By Abby Hagen (CAS`23)
Can mushrooms prevent aging? Chemistry Professor Pinghua Liu is trying to find out.
Liu has spent the past 18 years studying the biological clock and looking for potential methods to modulate or even reverse it. He hypothesizes that if our bodies can grow from birth through puberty, and later break down by following similar processes, there might be mechanisms that could be disrupted to slow down the aging process.
Biologists typically explore aging from cellular and metabolic levels, requiring a deep understanding of human body systems, such as the endocrine system’s role in hormone regulation. As a chemist, Liu wanted to take a different approach, using small molecules as the probes to stir up the aging process and extract useful aging-related information.
“We’re chemists. We need to make use of the strength of a chemist. We can make molecules and we can isolate natural products,” Liu says. “Longevity compounds can be tools to study how aging is recorded.”
After reading a book about Chinese botanical medicine, Liu was inspired by the success of Reishi mushrooms — used in cosmetics, dietary supplements, and growth stimulators — to rejuvenating human health. He decided to investigate how and why these mushrooms have been successful in Eastern medicine for thousands of years.
Liu found that the amino acid ergothioneine was responsible for the lifespan extension based on lifespan studies on worms and mice. Around the same time, ergothioneine was coined “the longevity vitamin” by Bruce Ames, a professor of Biochemistry and Molecular Biology Emeritus at the University of California, Berkeley. But because natural ergothioneine was so expensive — $50,000 per gram — it made further research untenable.
So Liu, along with BU Chemistry and Engineering Professors Qiang Cui, Sean Elliott, Mark Grinstaff, and Arturo Vegas and colleagues at Harvard Medical School, Carnegie Mellon University, the University of Connecticut, after characterizing several ergothioneine biosynthetic pathways, found a way to produce ergothioneine through engineered microbial enzymes — without exploiting or depleting natural sources of the compound.
Over several years, they have developed a process of producing ergothioneine at industry-scale levels, yielding as high as 40 grams per liter — significantly higher than a typical 1 gram per liter yield — enabling the mass production of ergothioneine for commercial use. As a result of this industry scale production, Liu and his colleagues had enough ergothioneine to begin animal trials on rats and mice to examine ergothioneine’s longevity effects.
Within six months, the trials started producing promising results. Initial observations showed significant differences on both the skin of the mice and the behavior of the mice, and after more than two years of study of a mouse’s lifespan in 2018, Liu and his colleagues found that ergothioneine could extend a mouse’s median lifespan by nearly 40 percent. “We found that the ‘longevity vitamin’ really lives up to its name,” Liu says. “The question remains what this means for understanding aging in humans.”
Applying these results to humans is complicated, Liu says, because a human’s life-span is so much longer than that of a mouse. “It’s not easy,” Liu says. “You can’t run human trials for longevity, it takes too long and there might be ethical issues to be considered too. So we turn to explore the potential applications of these longevity compounds as therapies for the aging associated diseases.”
For now, Liu and his colleagues are focused on understanding beneficial effects of ergothioneine on cardiovascular or neurological diseases like strokes etc. They are also connecting with colleagues from the BU Center for Aging Research and Skin Health, a new collaboration that brings together faculty from Arts & Sciences, Engineering, and the Chobanian & Avedisian School of Medicine.
“In terms of the longevity effect from mouse studies, this is the best small molecule so far,” Liu says. “The longer term goal is to use these products to increase quality of life for aging adults. We’re excited that the study of aging has started to get more attention and support in the last few years and look forward to seeing the difference that ergothioneine can make.”