The role of autophagy in the regulation of yeast life span

The role of autophagy in the regulation of yeast life span

Aging is a complex, multifactorial process that is driven by the progressive accumulation of several types of cellular damage. Functional impairment at the cellular level causes a multitude of pathologies and disorders in aged individuals. The goal of the aging field is to develop novel therapeutic interventions that extend human health span and reduce the burden of age-related disorders. To explore the molecular determinants that drive cellular aging, as well as how to slow them, researchers have utilized the highly genetically tractable budding yeast S. cerevisiae. Indeed, every intervention known to extend both cellular and organismal health span was identified in yeast, underlining the power of this approach. Importantly, a growing body of work has implicated the process of autophagy as playing a critical role in the delay of aging. This review summarizes recent reports that have identified a role for autophagy or autophagy factors in the extension of yeast lifespan. These studies demonstrate that yeast remains an invaluable tool for the identification and characterization of conserved mechanisms that promote cellular longevity for a number of reasons. Principal among them is the facility with which yeast can be genetically manipulated, as well as the fact that its genome has been well characterized. These features, combined with ease of growth and a short doubling time, conspire to make yeast highly amenable to a variety of high-throughput screening procedures. The use of yeast as an experimental system also allows for incomparably rapid lifespan experiments. Perhaps most importantly, since many of the pathways regulating longevity are conserved from yeast to more complex eukaryotes, including mammals, novel pharmaceutical or nutritional regulators of these processes that are identified in yeast will likely be translatable to the ultimate goal of delaying aging and improving the health span of humans. These studies also demonstrate that the process of autophagy has been implicated in nearly all known longevity-promoting manipulations and thus represent an ideal target for interventions aimed at improving human health span.

The role of autophagy in the regulation of yeast life span

Tyler JK, Johnson JE

Ann. N. Y. Acad. Sci. 2018 Jan;

PMID: 29363766

 

The goal of the aging field is to develop novel therapeutic interventions that extend human health span and reduce the burden of age-related disease. While organismal aging is a complex, multifactorial process, a popular theory is that cellular aging is a significant contributor to the progressive decline inherent to all multicellular organisms. To explore the molecular determinants that drive cellular aging, as well as how to retard them, researchers have utilized the highly genetically tractable budding yeast Saccharomyces cerevisiae. Indeed, every intervention known to extend both cellular and organismal health span was identified in yeast, underlining the power of this approach. Importantly, a growing body of work has implicated the process of autophagy as playing a critical role in the delay of aging. This review summarizes recent reports that have identified a role for autophagy, or autophagy factors in the extension of yeast life span. These studies demonstrate (1) that yeast remains an invaluable tool for the identification and characterization of conserved mechanisms that promote cellular longevity and are likely to be relevant to humans, and (2) that the process of autophagy has been implicated in nearly all known longevity-promoting manipulations and thus represents an ideal target for interventions aimed at improving human health span.

https://www.ncbi.nlm.nih.gov/pubmed/29363766

The integrated stress response in budding yeast lifespan extension

The integrated stress response in budding yeast lifespan extension

mic-04-368-g01The ultimate goal of aging research is to develop therapeutic means to extend human lifespan, while reducing susceptibility to many age-related diseases including cancer, as well as metabolic, cardiovascular and neurodegenerative disorders. However, this first requires clarification of the causes of aging, which has been greatly facilitated by the use of model organisms. In particular, the budding yeast Saccharomyces cerevisiae has been vital in the identification of conserved molecular and cellular determinants of aging and for the development of approaches to manipulate these aging determinants to extend lifespan. Past studies have shown that all means to experimentally extend lifespan result in the initiation of cellular stress responses which, in turn, increases the process of autophagy.

This review describes growing evidence in yeast that activation of the integrated stress response contributes significantly to lifespan extension. Thus, therapeutics to directly activate autophagy could be another promising approach to extend lifespan and healthspan. There are many different types of autophagy, and in order to have a better understanding of the aging process, it is crucial to know the specific autophagy pathways that need to be activated in order to extend yeast lifespan. This could then lead to the discovery of pharmaceutical and physiological regulators of these processes in yeast, which will likely have biological significance to human health and aging. It should also be noted that the impressive pace of research and discoveries being made using the yeast model organism indicate that it will continue to be a central model for aging studies in the near future.

You can find the full paper here.