How do you build and maintain a functioning cell for long periods of time?
Our laboratory studies how cells and tissues are maintained over long periods of time and how these processes are impacted by aging and disease. Maintenance of adult tissue architecture requires the coordination of pathways and nutrient metabolism within cells and cell populations in any given tissue, where dysregulation of these pathways underlies the loss of cell function and increases several disease risks.
We have developed imaging approaches that allow us to cross multiple scales in space and time to quantify the age of virtually any cell type (Arrojo e Drigo, Cell Metabolism 2019). This technology is called MIMS-EM and it leverages the resolution power of different types of microscopes to map the fine architecture of cells and to quantify the levels of specific stable isotope isoforms (i.e. 15N) retained by cellular structures. By quantifying the levels of 15N in cells or large protein complexes, without disrupting their tissue microenvironment, we are able to determine the age (or turnover rate) of target cells and structures. As a result, MIMS-EM allows us to visualize the age and organization of virtually any cell with high spatial and temporal resolution.
This platform led to the identification of several cell types in somatic organs that are largely post-mitotic and as old as neurons in the brain. Moreover, we identified long-lived protein complexes in the cell nucleus, cytoplasm and extracellular space.
This remarkable molecular and cellular longevity implies that these structures must have a fundamental resilience that allows them to survive in place for long periods of time; while at the same time exposing them to a potential accumulation of damage that likely occurs over their lifetime. Understanding how long-term cellular resilience is achieved (and maintained) is a very important question in biology, specially since human lifespan is very long.