Yeast at the Forefront of Research on Ageing and Age-Related Diseases

Abstract

Ageing is a complex and multifactorial process driven by genetic, environmental and stochastic factors that lead to the progressive decline of biological systems. Mechanisms of ageing have been extensively investigated in various model organisms and systems generating fundamental advances. Notably, studies on yeast ageing models have made numerous and relevant contributions to the progress in the field. Different longevity factors and pathways identified in yeast have then been shown to regulate molecular ageing in invertebrate and mammalian models. Currently the best candidates for anti-ageing drugs such as spermidine and resveratrol or anti-ageing interventions such as caloric restriction were first identified and explored in yeast. Yeasts have also been instrumental as models to study the cellular and molecular effects of proteins associated with age-related diseases such as Parkinson's, Huntington's or Alzheimer's diseases. In this chapter, a review of the advances on ageing and age-related diseases research in yeast models will be made. Particular focus will be placed on key longevity factors, ageing hallmarks and interventions that slow ageing, both yeast-specific and those that seem to be conserved in multicellular organisms. Their impact on the pathogenesis of age-related diseases will be also discussed.

PCK1Deficiency Shortens the Replicative Lifespan ofSaccharomyces cerevisiaethrough Upregulation ofPFK1

“…Aging is characterized by a progressive loss of physiological integrity, which was driven by a variety of contributing factors, including DNA damage, epigenetic shifts, and altered RNA and protein profiles [1][2][3]. e deterioration inevitably impairs tissue function and increases susceptibility to disease and death and has been demonstrated to be the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases [4].…”

Life-span extension by pigmented rice bran in the model yeast Saccharomyces cerevisiae

“…cerevisiae gene knockout system to identify new longevity factors and to determine the antioxidant and anti-aging potential of pigmented rice bran extract and compounds with the focus on their beneficial effect on chronological lifespan. Some candidates for anti-aging drugs, such as spermidine and resveratrol, and anti-aging interventions, such as caloric restriction, have been identified and explored in yeast 26 . Insights into the involved mechanism will help us to further explore other potential anti-aging agents.…”

Membrane-Interacting Antifungal Peptides

“…Moderate HsAFP1 doses induce autophagy in S. cerevisiae cells, probably as a fungal tolerance/pro-survival mechanism against the HsAFP1 action (Figure 2D; Struyfs et al, 2020). Since functional vacuoles are indispensable for the induction of autophagy (Martínez- Muñoz and Kane, 2008;Sampaio-Marques et al, 2019), they might play a role in governing tolerance to HsAFP1. Indeed, at high HsAFP1 doses vacuoles are affected, as demonstrated by the increased vacuolar pH, possibly resulting in impaired autophagy, and therefore in effective killing of S. cerevisiae cells.…”