Journal Club will be returning on August 27 with your host Dr. Oliver Medvedik and special guest Alexander Tyshkovskiy, a Ph.D. student who works at the Gladyshev at Brigham and Women’s Hospital, Harvard Medical School, Boston. The topic for the journal club this month will be the recent paper “Identification and Application of Gene Expression Signatures Associated with Lifespan Extension” published in Cell Metabolism. This study is Alexander Tyshkovskiy’s project and forms part of his Ph.D., so we are fortunate to have him joining us on the show to talk us through this fascinating study.
Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.
The show will be broadcast live on our Facebook page at 1:00 PM EDT on August 27, so come along and join us as we take a detailed look at this new study. The study paper is behind a paywall, but for those of you who support open access to science, you can access the paper freely on Sci-Hub here.
Tyshkovskiy, A., Bozaykut, P., Borodinova, A. A., Gerashchenko, M. V., Ables, G. P., Garratt, M., … & Gladyshev, V. N. (2019). Identification and Application of Gene Expression Signatures Associated with Lifespan Extension. Cell metabolism.