Lessons in Aging From a Single-celled Eukaryote: Unveiling Mechanisms of Chronological Lifespan Extension in Saccharomyces Cerevisiae

Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulatingS-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeastSaccharomyces cerevisiae. The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is theS. cerevisiaeortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed thatS-adenosyl-l-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.

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Saccharomyces cerevisiae displays an increased growth rate and an extended replicative lifespan when grown under respiratory conditions in the presence of bacteria

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0285 ◽

2017 ◽

Vol 63 (9) ◽

pp. 806-810

Author(s):

Paul A. Kirchman ◽

Nicholas Van Zee

Keyword(s):

Escherichia Coli ◽

Saccharomyces Cerevisiae ◽

Growth Rate ◽

Volatile Compound ◽

Lifespan Extension ◽

Yeast Saccharomyces Cerevisiae ◽

Replicative Lifespan ◽

Solid Media ◽

Respiratory Conditions ◽

Ferment Glucose

Individual cells of the budding yeast Saccharomyces cerevisiae have a limited replicative potential, referred to as the replicative lifespan. We have found that both the growth rate and average replicative lifespan of S. cerevisiae cells are greatly increased in the presence of a variety of bacteria. The growth and lifespan effects are not observable when yeast are allowed to ferment glucose but are only notable on solid media when yeast are forced to respire due to the lack of a fermentable carbon source. Growth near strains of Escherichia coli containing deletions of genes needed for the production of compounds used for quorum sensing or for the production of the siderophore enterobactin also still induced the lifespan extension in yeast. Furthermore, the bacterially induced increases in growth rate and lifespan occur even across gaps in the growth medium, indicating that the bacteria are influencing the yeast through the action of a volatile compound.

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Ehretiquinone from Onosma bracteatum Wall Exhibits Antiaging Effect on Yeasts and Mammals through Antioxidative Stress and Autophagy Induction

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5469849 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Yanjun Pan ◽

Yanan Liu ◽

Rui Fujii ◽

Umer Farooq ◽

Lihong Cheng ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Lifespan Extension ◽

Oxygen Species ◽

Replicative Lifespan ◽

Significant Evidence ◽

Chronological Lifespan ◽

Healthcare Product ◽

Autophagy Induction ◽

Type Molecule ◽

Antioxidative Stress

The antiaging benzoquinone-type molecule ehretiquinone was isolated in a previous study as a leading compound from the herbal medicine Onosma bracteatum wall. This paper reports the antiaging effect and mechanism of ehretiquinone by using yeasts, mammal cells, and mice. Ehretiquinone extends not only the replicative lifespan but also the chronological lifespan of yeast and the yeast-like chronological lifespan of mammal cells. Moreover, ehretiquinone increases glutathione peroxidase, catalase, and superoxide dismutase activity and reduces reactive oxygen species and malondialdehyde (MDA) levels, contributing to the lifespan extension of the yeasts. Furthermore, ehretiquinone does not extend the replicative lifespan of Δsod1, Δsod2, Δuth1, Δskn7, Δgpx, Δcat, Δatg2, and Δatg32 mutants of yeast. Crucially, ehretiquinone induces autophagy in yeasts and mice, thereby providing significant evidence on the antiaging effects of the molecule in the mammalian level. Concomitantly, the silent information regulator 2 gene, which is known for its contributions in prolonging replicative lifespan, was confirmed to be involved in the chronological lifespan of yeasts and participates in the antiaging activity of ehretiquinone. These findings suggest that ehretiquinone shows an antiaging effect through antioxidative stress, autophagy, and histone deacetylase Sir2 regulation. Therefore, ehretiquinone is a promising molecule that could be developed as an antiaging drug or healthcare product.

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