Discovery of fifteen new geroprotective plant extracts and identification of cellular processes they affect to prolong the chronological lifespan of budding yeast.

In a quest for previously unknown geroprotective natural chemicals, we used a robust cell viability assay to search for commercially available plant extracts that can substantially prolong the chronological lifespan of budding yeast. Many of these plant extracts have been used in traditional Chinese and other herbal medicines or the Mediterranean and other customary diets. Our search led to a discovery of fifteen plant extracts that significantly extend the longevity of chronologically aging yeast not limited in calorie supply. We show that each of these longevity-extending plant extracts is a geroprotector that decreases the rate of yeast chronological aging and promotes a hormetic stress response. We also show that each of the fifteen geroprotective plant extracts mimics the longevity-extending, stress-protecting, metabolic and physiological effects of a caloric restriction diet but if added to yeast cultured under non-caloric restriction conditions. We provide evidence that the fifteen geroprotective plant extracts exhibit partially overlapping effects on a distinct set of longevity-defining cellular processes. These effects include a rise in coupled mitochondrial respiration, an altered age-related chronology of changes in reactive oxygen species abundance, protection of cellular macromolecules from oxidative damage, and an age-related increase in the resistance to long-term oxidative and thermal stresses.

Mechanisms by which PE21, an extract from the white willow Salix alba, delays chronological aging in budding yeast.

We have recently found that PE21, an extract from the white willow Salix alba, slows chronological aging and prolongs longevity of the yeast Saccharomyces cerevisiae more efficiently than any of the previously known pharmacological interventions. Here, we investigated mechanisms through which PE21 delays yeast chronological aging and extends yeast longevity. We show that PE21 causes a remodeling of lipid metabolism in chronologically aging yeast, thereby instigating changes in the concentrations of several lipid classes. We demonstrate that such changes in the cellular lipidome initiate three mechanisms of aging delay and longevity extension. The first mechanism through which PE21 slows aging and prolongs longevity consists in its ability to decrease the intracellular concentration of free fatty acids. This postpones an age-related onset of liponecrotic cell death promoted by excessive concentrations of free fatty acids. The second mechanism of aging delay and longevity extension by PE21 consists in its ability to decrease the concentrations of triacylglycerols and to increase the concentrations of glycerophospholipids within the endoplasmic reticulum membrane. This activates the unfolded protein response system in the endoplasmic reticulum, which then decelerates an age-related decline in protein and lipid homeostasis and slows down an aging-associated deterioration of cell resistance to stress. The third mechanisms underlying aging delay and longevity extension by PE21 consists in its ability to change lipid concentrations in the mitochondrial membranes. This alters certain catabolic and anabolic processes in mitochondria, thus amending the pattern of aging-associated changes in several key aspects of mitochondrial functionality.