TY - JOUR T1 - Species comparison of liver proteomes reveals enhanced lipid metabolism, reduced mitochondrial respiration and enhanced expression of detoxifying enzymes in the long-lived naked mole-rat JF - bioRxiv DO - 10.1101/220343 SP - 220343 AU - Ivonne Heinze AU - Martin Bens AU - Enrico Calzia AU - Susanne Holtze AU - Oleksandr Dakhovnik AU - Arne Sahm AU - Joanna M. Kirkpatrick AU - Karol Szafranski AU - Natalie Romanov AU - Stephan Singer AU - Maria Ermolaeva AU - Matthias Platzer AU - Thomas Hildebrandt AU - Alessandro Ori Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/20/220343.abstract N2 - Mammals display wide range of variation in their lifespan. Lifespan is generally correlated to body size, but outliers such as human and the naked mole-rat (NMR, Heterocephalus glaber) exist. Investigating the molecular networks that distinguish long‐ from short-lived species has proven useful to identify determinants of longevity. Here, we compared the liver of long-lived NMRs and the phylogenetically closely related, shorter-lived, guinea pigs (GP, Cavia porcellus) using an integrated transcriptomic and proteomic approach. We found that NMRs express substantially higher levels (up to 30 fold) of a restricted number of longevity-associated proteins that confer enhanced buffering against oxidative stress. Moreover, NMR livers display a unique expression pattern of mitochondrial proteins that result in distinct metabolic features of their mitochondria. For instance, we observed a generally reduced respiration rate associated with lower protein levels of respiratory chain components, particularly complex I, and increased capacity to utilize fatty acids. Interestingly, the same molecular networks are affected during aging in both NMR and humans, supporting a direct link to the extraordinary longevity of both species. Finally, we used our analysis to identify novel longevity pathways, and validated one of them experimentally in the phylogenetically distantly related nematode C. elegans. ER -