Fabio Demontis Lab

The progressive decline in skeletal muscle mass and function that occurs with aging (sarcopenia) is a deleterious condition that reduces survival and increases the risk of age-related disease in non-muscle tissues. Our work determined that the decline in proteostasis is a cause of age-related skeletal muscle dysfunction and that sarcopenia can be impeded by preserving protein quality control via proteases and the ubiquitin/proteasome and authophagy/lysosome systems. 

Our research seeks to understand fundamental new mechanisms of protein quality control in the skeletal muscle and central nervous system and their role in aging and age-related diseases.

Systemic homeostasis relies on inter-organ crosstalk, with such inter-tissue communication becoming deranged during aging. Epidemiological surveys and studies in model organisms indicate that signals released by healthy muscles can protect the CNS from the effects of aging and, conversely, muscle dysfunction is deleterious for brain and systemic aging. Our laboratory examines this connection between the skeletal muscle and the CNS. In particular, we study muscle-secreted signaling factors (myokines and myometabolites) that signal to the brain and retina. Skeletal muscle can release such signaling factors in response to exercise and related processes, such as the unfolded protein stress response, nutrient sensing, and pro-longevity pathways.

Our work strives to identify key muscle-secreted factors that protect the CNS from the age-related loss of proteostasis. Additionally, we want to understand how myokines regulate normal brain function, such as in the initiation of feeding behavior and sleep.

We are broadly interested in aging and age-related processes and their impact on human disease. As an example, we work to identify interventions to boost muscle regeneration and understand how cancer-induced muscle and systemic wasting (cachexia) is influenes by aging. Research in this area may highlight vulnerabilities of pediatric versus adult cancers and provide interventions to preserve skeletal muscle mass and function in 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.