The role of ribosomes in calorie restriction mediated lifespan extension
Denis Titov, Assistant Adjunct Professor
Nutritional Sciences and Toxicology
Closed. This professor is continuing with Spring 2024 apprentices on this project; no new apprentices needed for Fall 2024.
Aging is the greatest risk factor for numerous chronic conditions such as cancer, cardiovascular disease, and neurodegeneration. Once thought to be an uncontrollable stochastic process due to an accumulation of damage over time, genes and regulatory networks have been discovered that modulate the rate of aging. Supported by data in laboratory models, the hope of geroscience research is that by targeting and delaying the rate of aging itself – instead of individual diseases – this would simultaneously delay the onset of age-associated disorders. Caloric restriction is one of the most robust interventions known to extend lifespan and delay the onset of age-associated diseases in laboratory animals. Despite being first reported nearly a century ago, the complete underlying pathways that mediate this anti-aging intervention continue to remain elusive. By using quantitative label-free proteomics, we have identified that calorie restriction leads to a significant down-regulation in ribosomal levels. A down-regulation in ribosomal levels and translation rates remains another longstanding intervention that robustly extends lifespan in multiple organisms. Therefore, the goal of this project is to test a model that converges these two longevity pathways: namely, that caloric restriction achieves its lifespan extending effects by decreasing ribosomal levels.
Role: Over the course of this project, students will gain proficiency with a cross-disciplinary training of molecular biology, metabolism, and computational techniques with the goal of becoming an independent researcher. Specific techniques will include: (1) Assessing ribosomal levels through western blotting (2) proper handling and execution of Caloric Restriction experiments in C. elegans as the model system we will be working with (3) computational data analysis using a custom-built distributed microscope for automated lifespan detection. Many more skills can be taught depending on how engaged and eager the student is to learn. Importantly, throughout this process, students will learn how to critically think, design, and optimize experiments to test hypotheses.
If interest and productivity persist throughout the semester, there will be opportunities to continue this project in future semesters. With greater involvement, support will be given if there is interest to use this research as an honors thesis. All contributions to the advancement of the project will lead to inclusion as an author on future presentations and publications.
Qualifications: Undergraduates seeking to apply should be: (1) eager to learn (2) have high attention to detail (3) highly motivated and organized (4) perseverant and hard working (5) be open to ask questions and learn from mistakes. Previous research experience is not required, although previous experience in working with C. elegans would be considered valuable. Significant hands on mentorship will be given to the student selected and therefore the amount of time available the student has to commit to research will be taken into consideration.
Day-to-day supervisor for this project: Bowen Yang
Hours: 12 or more hours
Related website: https://denistitovlab.org/
Biological & Health Sciences