Hetzer Group

Protein homeostasis and aging

Old age is the major risk factor for the development of neurodegenerative diseases such as Alzheimer’s disease and a series of other ailments. The Hetzer lab is studying the impact of cumulative changes during adulthood on health and the development of disease, focusing on cell maintenance and repair mechanisms. They are particularly interested in understanding how non-dividing cells such as neurons function over the course of a lifetime and how cells lose control over the quality and integrity of proteins and important cell structures during aging. The ultimate goal is to utilize these mechanisms to delay age-related decline of organs with limited cell renewal such as the brain, pancreas and heart.

The group applies genomics, proteomics and advanced imaging techniques to pose questions about how adult tissues are maintained and repaired and why long-lived cells fail to work properly as a cell ages. Recent studies have shown that mammalian tissues are mosaics composed of cell populations with vastly different life spans ranging from days to years. The Hetzer laboratory discovered long-lived proteins (LLPs) in the nucleus, which exhibit no or very little protein turnover in the adult brain. The functional decline of LLPs could be a major contributor to age-related changes in the survival of nerve cells. A focus of his lab is to understand what allows LLPs to stay intact throughout an organism’s entire life span. In people with neurodegenerative diseases, it appears that LLPs in older cells lead to the decline of the nucleus. Understanding why this happens is the first step to potentially prevent and treat disorders like Alzheimer’s disease.