Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

Abstract

Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.

Characterization of Resveratrol, Oxyresveratrol, Piceatannol and Roflumilast as Modulators of Phosphodiesterase Activity. Study of Yeast Lifespan

“…As previous results demonstrated, the deletion of yPDE2 decreases the lifespan of the cell [4,16]. However, this pharmacological reversible inhibition seems to increase the lifespan, perhaps any internal yPDE2 up-down regulation [34] or due to the multitasking and different targets of RSV such as Sir2, which also affects lifespan [5,20]. In addition, this is the first time that roflumilast, a common PDE4 inhibitor drug for chronic obstructive pulmonary disease has been studied in lifespan studies although the use of roflumilast to mimic CR has been tested successfully previously [22].…”

“…Although this pathway has been studied in several animal models, Saccharomyces cerevisiae is one of the most useful models since it is easy to handle and they present several pathways conserved from multicellular eukaryotes [ 1 ]. Although there are different ways to manage lifespan [ 3 ], the cAMP-PKA signaling mechanism is one of the keys [ 4 , 5 ]. In CR, some molecules and conditions modulate PKA [ 1 , 6 ] by increasing cAMP levels ( Figure 1 A) suggesting phosphodiesterases (PDEs)—enzymes that convert cAMP into AMP—as possible targets to promote a CR response.…”

Implication of ferroptosis in aging

“…However, iron accumulates in the tissues with increasing age, pointing towards the incompetence of iron regulatory mechanisms that prevent abnormal redox cycling of iron, such as the Fe 2+ -glutathione complexes [54]. Moreover, this phenomenon of iron accumulation with aging is conserved and represents a remote consensus for susceptibility in late stages of life in many organisms including drosophila, nematodes, mammals, and humans [55][56][57][58]. Research is going on to prove the susceptibility of aged animals to ferroptotic death due to agerelated increment of labile iron coupled with a reduction of glutathione levels implying that disruption to the iron-glutathione axis is fundamental to natural aging and death.…”

Targeted Deletion of Los1 Homologue Affects the Production of a Recombinant Model Protein in Pichia pastoris

“…The budding yeast, S. cerevisiae , has been an excellent model for aging and lifespan-related studies. Both RLS (the number of daughter cells generated by a mother cell before replicative senescence) and CLS (the survival time of a yeast cell in non-dividing condition) have already been defined, and molecular mechanisms involved in the yeast lifespan have been investigated in details [ 9 , 10 ] . So far, several genes identified in yeast have been shown to be able to modulate the aging process through different mechanisms [ 11 , 12 ] .…”