Dissecting the role of proteostasis and muscle-to-brain signaling in aging and age-related diseases
Aging is the major risk factor for many human diseases. A better understanding of the cellular and molecular mechanisms of aging may provide a means for interventions that cure or prevent age-related diseases. Our laboratory’s work focuses on the role of protein quality control (proteostasis) and how aging deranges this process in skeletal muscle and the central nervous system. In addition to cell-autonomous mechanisms of proteostasis, we work to understand how communication between skeletal muscle and the brain influences proteostasis as we age.
Aging is the major risk factor for many diseases, but the underlying mechanisms are not completely understood. As we age, our bodies experience degenerative changes that impact organ and cellular functions. These degenerative changes include the loss of protein quality control (proteostasis), which reduces the capacity of the cell to breakdown and remove faulty proteins and ensure the normal turnover of proteins. This loss of protein quality control causes many age-related diseases, such as neurodegeneration and decline in skeletal muscle function.
To broaden our understanding of this degenerative change, our laboratory examines the role of protein quality control in aging and age-related diseases in skeletal muscle and the central nervous system. We further examine signaling factors produced by skeletal muscle to discover how healthy muscles can help preserve brain function and proteostasis during aging. Our goal is to dissect fundamental mechanisms of proteostasis and muscle-to-brain signaling so we can understand how to preserve and extend a healthy lifespan in humans.
Protein quality control in skeletal muscle aging
The progressive decline in skeletal muscle mass and function that occurs with aging (sarcopenia) and disease is a deleterious condition that reduces survival and increases the risk of age-related disease development in non-muscle tissues. Our work determined the decline in proteostasis is a cause of age-related skeletal muscle dysfunction and preservation of protein quality control impedes sarcopenia.
Our research seeks to understand the mechanisms of skeletal muscle aging and disease-associated wasting. In addition to skeletal muscle, we work to dissect fundamental mechanisms of protein quality control that may have general protective roles across tissues during aging and age-related diseases.
Influence of myokine signaling on brain proteostasis and aging
Aging is a process that relies on the interaction between skeletal muscle and other tissues, in which healthy skeletal muscle protects the central nervous system from the effects of aging. Because of this relation, our laboratory examines the connection between skeletal muscle and the central nervous system, specifically the influence of muscle-secreted factors (myokines) on brain aging. Skeletal muscle can release signaling factors in response to exercise and related processes, such as the unfolded protein stress response and nutrient-sensing and pro-longevity pathways.
Our work strives to identify key muscle-secreted factors that protect the central nervous system from age-related neurodegeneration. More broadly, we strive to develop an understanding of the role of myokines in regulating physiological brain functions, such as feeding behavior. Altogether, our work in this area shows the importance of skeletal muscle in regulating brain function and proteostasis.
Intersection of aging and muscle biology with human disease
Other areas of aging and muscle biology, as they intersect with human disease, are of great interest to our laboratory. We work to understand the mechanisms of cancer-induced muscle wasting (cachexia) and how aging influences these mechanisms. Research in this area may highlight vulnerabilities of pediatric versus adult cancers and provide interventions to preserve skeletal muscle mass and function as well as extend survival of cancer patients and cancer survivors.
All areas of our work benefit from our employment of varying experimental models and the collaboration with other labs working on related topics, as we seek insights into the complex regulation of proteostasis and inter-tissue signaling during aging.