Supersulfides maintain yeast homeostasis and may play a role in longevity: Findings from Nara Institute of Science and Technology

A joint research group led by Assistant Professor Akira Nishimura of the Graduate School of Science and Technology and Specially Appointed Professor Hiroshi Takagi of the Institute for Research Initiatives at the Nara Institute of Science and Technology, and Professor Takaaki Akaike of the Graduate School of Medicine at Tohoku University discovered that supersulfides control the longevity of yeast. Since this longevity-controlling mechanism in yeast is expected to be widely conserved in higher organisms (including humans), supersulfides may contribute to the prevention of human aging and the extension of a healthy lifespan. The study results were published in the academic journal Redox Biology.

Supersulfides are compounds characterized by a polysulfide structure wherein sulfur atoms are polymerized and catenated, forming self-linked bonds. They have been attracting attention as unique active substances responsible for both oxidation and reduction reactions in living organisms.

Around a decade ago, Akaike and his colleagues made a discovery by identifying substantial quantities of supersulfides within living organisms. Since then, they have been engaged in research aimed at unraveling the scientific characteristics of these sulfur species and their physiological impacts. In the current study, the group speculated on the role of these compounds in maintaining organismal homeostasis, particularly in relation to longevity, employing yeast for the research.

They utilized budding yeast as a eukaryote model to engineer a mutant strain incapable of synthesizing supersulfides. Upon detailed analysis of the mutant, the researchers discovered a significant reduction in the longevity of the yeast. The analysis revealed that they play a crucial role in the oxidation and reduction activities of protein disulfide isomerase (PDI), an enzyme involved in regulation of proteins in the endoplasmic reticulum, and that supersulfides are responsible for regulating the quality of proteins in the endoplasmic reticulum.

They found that they are also involved in maintaining mitochondrial energy metabolism. They further observed that the external addition of supersulfides prolonged the longevity of the yeast. The compounds regulate longevity by mitigating endoplasmic reticulum stress which arises from the accumulation of structurally abnormal proteins, and by enhancing energy metabolism. In other words, the ingestion of supersulfides may promote a healthy lifespan and prevent aging-related diseases.

The longevity-controlling mechanism of supersulfides could be highly conserved in higher organisms, including humans. Therefore, their supplemental ingestion may extend the healthy lifespan and prevent aging-related diseases in humans as well.

In the future, the research group aims to elucidate the fundamental mechanism underlying longevity control by supersulfides. They intend to gather scientific evidence to advance the social implementation of futuristic medical care driven by these sulfur molecules.

Journal Information
Publication: Redox Biology
Title: Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality
DOI: 10.1016/j.redox.2023.103018