Mechanisms Underlying Longevity Regulation and Extension by Genetic, Dietary and Pharmacological Interventions in the Yeast Saccharomyces Cerevisiae

摘要: This thesis describes studies in which the yeast Saccharomyces cerevisiae was used as a model organism for unveiling mechanisms underlying longevity regulation and extension by genetic, dietary and pharmacological interventions. We found that diet known caloric restriction (CR) modulates oxidation-reduction processes reactive oxygen species (ROS) production mitochondria, reduces frequency of mitochondrial DNA (mtDNA) mutations, alters abundance mtDNA-binding activity nucleoid-associated proteins. Our findings provide evidence these play essential roles regulating chronologically active defining their viability following cell entry into quiescent state. Based on findings, we propose hypothesis ROS, are mostly generated by-products respiration, dual role aging yeast. On one hand, if yeast mitochondria unable (due to regimen) maintain ROS concentration below toxic threshold, promote oxidatively damaging certain mitochondrial proteins mtDNA. other mitochondria can at “optimal” level, delay chronological aging. this level is insufficient damage cellular macromolecules but activate signaling networks extend lifespan increasing or stress-protecting anti-aging In addition, presented imply mtDNA mutations do not contribute grown under non-CR conditions make important contribution placed CR diet. The nonreducing disaccharide trehalose has been long considered only reserve carbohydrate. However, recent suggested osmolyte protect cells proteins from oxidative elicited exogenously added ROS. Trehalose also shown affect stability, folding aggregation bacterial and firefly heterologously expressed heat-shocked cells. investigation how lifespan-extending metabolic history programmed capacity - including biosynthesis degradation developed prior quiescence. To investigate whether homeostasis may extension CR, examined single-genedeletion affecting impact 1) agerelated dynamics changes concentration; 2) lifespan conditions; 3) chronology protein damage, intracellular ROS level aggregation; 4) timeline thermal inactivation its subsequent reactivation returned low temperature. data extends altering pattern age-related concentration.