Title | Is Gcn4-induced autophagy the ultimate downstream mechanism by which hormesis extends yeast replicative lifespan? |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Shen Z-J, Postnikoff S, Tyler JK |
Journal | Curr Genet |
Volume | 65 |
Issue | 3 |
Pagination | 717-720 |
Date Published | 2019 Jun |
ISSN | 1432-0983 |
Keywords | Autophagy, Basic-Leucine Zipper Transcription Factors, Gene Expression Regulation, Fungal, Hormesis, Longevity, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins |
Abstract | The number of times a cell divides before irreversibly arresting is termed replicative lifespan. Despite discovery of many chemical, dietary and genetic interventions that extend replicative lifespan, usually first discovered in budding yeast and subsequently shown to apply to metazoans, there is still little understanding of the underlying molecular mechanisms involved. One unifying theme is that most, if not all, interventions that extend replicative lifespan induce "hormesis", where a little inflicted damage makes cells more able to resist similar challenges in the future. One of the many cellular changes that occur during hormesis is a global reduction in protein synthesis, which has been linked to enhanced longevity in many organisms. Our recent study in budding yeast found that it was not the reduction in protein synthesis per se, but rather the subsequent induction of the conserved Gcn4 transcriptional regulator and its ability to induce autophagy that was responsible for extending replicative lifespan. We propose that Gcn4-dependent induction of autophagy occurring downstream of reduced global protein synthesis may be a unifying molecular mechanism for many interventions that extend replicative lifespan. |
DOI | 10.1007/s00294-019-00936-4 |
Alternate Journal | Curr Genet |
PubMed ID | 30673825 |
PubMed Central ID | PMC6511304 |
Grant List | RO1 CA95641 / / National Institutes of Health / RO1 GM64475 / / National Institutes of Health / R01 AG050660 / AG / NIA NIH HHS / United States R01 GM064475 / GM / NIGMS NIH HHS / United States RO1 AG050660 / / National Institute on Aging / |
Related Faculty:
Jessica K. Tyler, Ph.D.