During aging, many biological processes go out of balance. Changes are apparent at the level of the whole animal, tissues, cells, molecules, and metabolism. We believe that changes at the molecular level drive the changes at higher levels. Animals have extensive endogenous mechanisms that maintain balance (homeostasis) in young animals. These homeostatic mechanisms degrade with age. We believe that we can prevent this degradation and re-engage these maintenance systems in older animals, which will prevent disease and extend lifespan. The Lithgow lab concentrates on identifying small drug-like molecules that re-engage and enhance homeostatic mechanisms in the microscopic nematode worm C. elegans. We aim to boost mechanisms that prevent protein misfolding and remove damaged proteins and other forms of molecular damage. Frequently, treatment with such molecules results in lifespan extension and postpones disease pathology. We now collaborate with other Buck researchers to test the effectiveness of these compounds to prevent chronic disease in mouse models.