Pharmaceutical and genetic interventions to understand mechanisms of aging in C. elegans

Aging, long considered passive and irreversible, is now known to be regulated by a number of cellular processes. As aging is the major risk factor for the majority of chronic diseases, such as cancer, cardiovascular disease, neurodegenerative diseases and even severe outcomes of transmissible diseases such as COVID-19, understanding how to slow these pathways is critical to human well-being. Interventions in aging processes are termed ‘geroprotective,’ as they protect the gerontological phase of life. In this thesis, we aimed to contribute to the understanding of aging mechanisms and treatment of age-related diseases by (1) investigating mitochondrial dysfunction as a hallmark of aging, (2) identifying and validating geroprotective pharmaceuticals, and (3) utilizing these pharmaceuticals to deepen understanding of aging mechanisms in the common aging model organism, the nematode Caenorhabditis elegans.
The work of this thesis identifies geroprotective interventions, both genetic and pharmaceutical, that give insight into how the aging process works. Many of the mechanisms we describe provide additional evidence for the hormetic theory of longevity. This theory suggests that stressors, while toxic at high doses, produce health benefits and can extend lifespan in lower doses. Though there are many considerations in translating geroprotective interventions to humans, eventually some of our findings could lead to treatments to reduce frailty or treat age-related diseases.