Modern science has scoured the planet for naturally-occurring compounds that might hold medicinal benefits. For example, rapamycin, perhaps the most well-researched compound known to extend the lifespans of multiple species, was isolated from a bacterium found in the soil of Easter Island. The natural world seems to hold a veritable pharmacy of compounds waiting to be discovered, and pharmaceutical companies continue to catalog samples from all corners of the globe, compiling an ever-growing library of compounds with which they interrogate all manner of biological pathways in the hopes of discovering the next ground-breaking drug. Of course, many cultures have spent centuries compiling their own medicinal libraries, mostly comprised of plants thought to be imbued with beneficial properties. The traditional Chinese medical pharmacopeia contains a multitude of specimens purported to improve healthspan.
A recent publication in Nature Communications examined numerous examples of plants commonly used in traditional Chinese medicine. Utilizing the lifespan assay known as the yeast mother enrichment program, researchers assessed crude extracts of candidate plants and identified the herb Psoralea corylifolia to have potential lifespan-extending properties. Further analysis demonstrated a single compound, corylin, to be responsible for improving lifespan; it was shown to function through the mTOR pathway, a well-defined pathway known to modulate lifespan in a multitude of organisms.
Although the mTOR pathway is highly conserved and its inhibition is known to extend lifespan in a variety of species including both yeast and mammalian, these species have significant differences. To explore if corylin’s actions in yeast might have a related effect in mammalian systems, the authors turned to in vitro experiments. Human umbilical vein endothelial cells treated with corylin showed significantly decreased markers of senescence, an important finding as senescence is highly correlated with aging in multicellular organisms and thought to be a driver of an aging phenotype. Additionally, gene expression patterns of older cells treated with corylin were similar to those of younger cells. These findings encouraged the authors to the expand the scope of their study to examine corylin effects in mice.
Mice were fed a high-fat diet similar to that of modern western peoples and known to induce multiple pathologies, e.g., obesity, cardiovascular disease, diabetes, dyslipidemia, and chronic inflammation. Interestingly, corylin supplementation did not reduce body weight, yet it improved numerous obesity-related pathologies. Circulating levels of total cholesterol (as well as HDL and LDL) and triglycerides were found to be reduced, suggesting improvement to cardiovascular health. Levels of aspartate transaminase and creatinine, common markers of liver and kidney function, respectively, improved in corylin supplemented animals. Additionally, fasting glucose was significantly reduced, suggesting systemic improvements in metabolic function despite corylin’s inability to reduce body weight due to a high-fat diet. In accordance with the metabolic improvement, corylin supplementation also improved the physical function of older mice, assessed via multiple standardized measurements to determine muscle strength, balance, and endurance.
Not surprisingly, the lifespan of corylin-treated mice was also shown to increase. Assessed at 102 weeks of age, 63.3% of animals fed a high-fat diet had died as compared to only 43.3% of the corylin-treated group. Additionally, survivability at earlier time points showed an even greater benefit to corylin-supplemented mice with a maximum improvement of 30%. The paper did not report the survival of all animals over the duration of their lives; however, having observed such significant differences in percent survival, it is reasonable to conclude that corylin will have a similarly sustained effect over the entire life of these animals.
Western diets are considered to be a major contributor to poor health and the acceleration of age-related disease. This is especially important in the context of this study considering the Western diet is analogous to the high-fat diet fed to the study animals and the various improvements to health parameters observed in corylin-treated animals. The Western diet is quickly becoming no longer relegated to Western peoples; many cultures around the world are adopting similar diets and as a result becoming subject to poor health outcomes. Corylin might have the potential to alleviate a portion of diet-induced stress seen in people consuming these less-than-ideal diets.