Abstract
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.
Highlights
The budding yeast Saccharomyces cerevisiae is a widely used model organism in aging research because it offers three significant advantages in studying mechanisms of aging and longevity [1,2,3,4,5]
We revealed that the six plant extracts (PEs) extend yeast chronological lifespan (CLS) through different signaling pathways and protein kinases converged into a network; this network is known to define the rate of chronological aging in S. cerevisiae and to regulate longevity in other eukaryotic organisms [34]
Cells of budding yeast cultured under such non-caloric restriction conditions are known to age chronologically faster than the ones cultured under CR conditions on 0.2% (w/v) or 0.5% (w/v) glucose [1, 3, 4, 33]
Summary
The budding yeast Saccharomyces cerevisiae is a widely used model organism in aging research because it offers three significant advantages in studying mechanisms of aging and longevity [1,2,3,4,5]. S. cerevisiae is amenable to comprehensive molecular analyses that have been used to uncover mechanisms of various cell biological processes [4, 6,7,8,9,10]. Because of these advantages, studies in S. cerevisiae discovered many genes, signaling pathways and chemical compounds that, following their discovery in budding yeast, were implicated in aging and longevity in organisms across an evolutionary tree [4, 5, 8, 11,12,13,14,15]. It is commonly believed that the major aspects and underlying mechanisms of aging and aging-associated pathology have been conserved throughout evolution [8, 14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]
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