Journal Club August 2019 – Finding Life-Extension Signatures

The Journal Club on August 27 was hosted by Dr. Oliver Medvedik and special guest Dr. Alexander Tyshkovskiy, who works at the Gladyshev at Brigham and Women’s Hospital, Harvard Medical School, Boston. The topic was the recent paper “Identification and Application of Gene Expression Signatures Associated with Lifespan Extension” published in Cell Metabolism. This study was Dr. Alexander Tyshkovskiy’s project and formed part of his Ph.D. and we are very grateful to him for taking the time to join us for this special episode of the Journal Club and share his personal insights into the study and talk us through the wealth of information contained within it.

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 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.

Literature

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.