PHASE I – WORK PLAN
Comparative Biology
Projects in Comparative Biology
A Comprehensive Biobank of Mammalian Species with a Variation of Lifespans
The animal kingdom of mammals exhibits a remarkable 200-fold variation in lifespan, from short-lived rodents to long-lived whales. This project aims to establish a comprehensive biobank of samples from 200+ mammalian species across the phylogenetic tree, representing a wide range of lifespans. This biobank will serve as a valuable tool for unraveling the complex biology of aging across mammals.
Multispecies Comparison of the Mechanisms of Natural Radical Lifespan Extension
This project aims to uncover the fundamental molecular mechanisms determining lifespan variation across species through multi-level omics profiling of 200+ mammals. By analyzing diverse tissues across species with varying lifespans, we seek to identify common and lineage-specific longevity strategies, understand their effects on aging, and discover key regulators of lifespan. The study will employ cutting edge technologies including RNA-seq, proteomics, metabolomics, lipidomics, glycomics, epigenomics, and single-cell analyses to generate a comprehensive dataset for comparative aging biology, allowing to answer questions like “Why is there a 200-fold difference in mammalian lifespan?”.
A Catalog of induced Pluripotent Stem Cells (iPSCs) of 50 Non-Model Organisms to Scale Comparative Biology Research
This pioneering project aims to develop, acquire and characterize 50 induced pluripotent stem cell (iPSC) lines from diverse organisms, primarily focusing on mammals, and a few birds and reptiles with varying lifespans. By establishing this comprehensive iPSC resource, we seek to overcome the practical and ethical challenges associated with studying wild, rare, and endangered species in comparative biology research. The resulting iPSC collection will serve as a valuable tool for the scientific community, enabling in vitro studies of lifespan control and longevity mechanisms across phylogeny. These cell lines will facilitate the investigation of cellular and molecular traits associated with exceptional longevity and disease resistance observed in certain species.
Creation and Characterization of Interspecies Chimeras Between Short and Long-Lived Species to Study Cross-Species Effects of Lifespan
This project aims to create and characterize interspecies chimeras between short and long-lived species to investigate the cellular and molecular basis of longevity. By generating chimeras using iPSCs from long-lived species (such as blind mole-rats or bats) and mouse embryos, we will explore whether longevity traits can be transferred across species and how genes from long-lived species behave in a different biological context. Additionally, we will assess the impact of these chimeras on host lifespan and healthspan, and investigate the potential for engineering enhanced longevity traits.
Investigating the Impact of Long-Lived Species Adaptations on Mouse Longevity
This project aims to investigate the potential synergistic effects of combining longevity-associated genes from long-lived species (LLS) in mice. By creating transgenic mouse strains expressing multiple genes identified in LLS, we will test whether this combinatorial approach can extend healthspan and lifespan in a short-lived species. The experiment will involve generating single and multi-transgenic mouse lines, with inducible expression systems, and evaluating their healthspan, lifespan, and stress resistance. This research could provide crucial insights into the complex nature of aging and the potential for multi-pathway interventions to significantly alter the aging trajectory.