Wescombe, P. A. | Search bioRxiv

bioRxiv2023

Reevaluating the Concept of Aging: Long-Term Stress Adaptation as a Key Factor in Yeast Aging

It has been demonstrated that short-term stress can enhance cellular responses and promote longevity, whereas long-term stress shortens lifespan. Understanding the relationship between short-term and long-term stress could offer new insights into comprehending and modulating age-related diseases. In this study, we investigate this relationship using transcriptomic and metabolomic analyses in the yeast model system (Saccharomyces cerevisiae). We employed three metabolic treatments: firstly, treating yeast cells with threshold levels of benzoic acid for 24 hours (Short-term [ST] Stressed Cells); secondly, treating yeast cells with threshold levels of benzoic acid for 500 hours, with sub-culturing every 24 hours (Long-term [LT] Stressed Cells); and thirdly, allowing the long-term stressed cells to grow for 16 hours without any benzoic acid (Recovered Cells). Here, we propose that aging is an evolutionarily conserved cellular adaptation mechanism in response to long-term stress exposure. Under short-term stressed conditions, prominent lifespan-extending metabolites such as trehalose and metabolites linked to tumor suppression in humans, such as 5-methylthioadenosine, were overexpressed. In contrast, LT Stressed Cells activated genes such as those responsible for epigenetic regulatory enzymes that govern the aging process, and secondary stress response genes, such as heat shock proteins (HSPs) which are associated with adaptation to cell damage but also often associated with aged cells. Chronological lifespan experiments showed that LT stressed cells lived a shorter lifespan compared to ST Stressed Cells. This suggests that the markers of aging (eg. HSPs, certain epigenetic regulators) are expressed in response to long-term stress to enable cell survival but have the long-term effect of reducing lifespan. In support of this hypothesis, we also show that genes exclusively activated in ST Stressed Cells are conserved solely in eukaryotes, while those significantly expressed in LT Stressed Cells (aging related) exhibit high conservation across all domains of life, with a majority having originated from bacteria hinting at the potential evolutionary benefit of aging.

cell biology↗

bioRxiv2022

Epigenetic Changes in Saccharomyces cerevisiae Alters the Aromatic Profile in Alcoholic Fermentation

Epigenetic changes in genomics provide phenotypic modification without DNA sequence alteration. This study shows that benzoic acid, a common food additive and known histone deacetylase inhibitor (HDACi), has an epigenetic effect on Saccharomyces cerevisiae. Benzoic acid stimulated formation of epigenetic histone marks H3K4Me2, H3K27Me2, H3K18ac and H3Ser10p in S. cerevisiae and altered their phenotypic behavior, resulting in increased production of phenylethyl alcohol and ester compounds during alcoholic fermentation. Our study demonstrates the HDACi activity of certain dietary compounds such as sodium butyrate, curcumin and anacardic acid, suggests the potential use of these dietary compounds in altering S. cerevisiae phenotypes without altering host-cell DNA. This study highlights the potential to use common dietary compounds to exploit epigenetic modifications for various fermentation and biotechnology applications as an alternative to genetic modification. These findings indicate that benzoic acid and other food additives may have potential epigenetic effects on human gut microbiota, in which several yeast species are involved. ImportanceThis manuscript investigates and reports for the first time utilizing microbial epigentics to alter the fermentation process of Pinot noir wines. We have experimentally demonstrated that certain dietary epigenetic compounds possess histone deacetylase (HDAC) inhibiting activity and can alter the wine characteristics by altering yeast gene expression. We have coined the term nutrifermentics to represent this newly proposed field of research, which provides insights on the effect of certain dietary compounds on microbial strains and their potential application in fermentation process. This technological approach is a novel way to manipulate microorganisms for innovative food and beverage production with quality attributes.

microbiology↗