A study, published in 2019, provided a comprehensive analysis of 17 known lifespan-extending interventions in mice at the level of gene expression, to better signatures associated with longevity. They then applied these signatures to predict new candidate compounds for lifespan extension
Many dietary, genetic and pharmacological interventions that increase mammalian lifespan are known, but the general principles of lifespan extension remain unclear.
Researchers performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. Discovering a feminizing effect associated with growth hormone regulation and diminution of sex-related differences.
Expanding this analysis to 17 interventions with public data, it was found many interventions induced similar gene expression changes. Hepatic gene signatures associated with lifespan extension across interventions were identified, including upregulation of oxidative phosphorylation and drug metabolism.
The team applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Presenting appealing candidates for further investigation.
Currently, we are validating these hits by testing their effect on the mouse lifespan. We hope that our biomarkers will significantly facilitate the search for new longevity interventions and help improve the healthspan and lifespan in rodents and, in the long term, in humansAlex Tyshkovskiy, lead author