Mills Lab

The broad focus of our research group is to define the molecular pathways that regulate aging and age-related diseases.   In diverse organisms ranging from worms to mammals, the over-consumption of food dramatically decreases lifespan and calorie restriction markedly slows the rate of aging.  Obesity is caused by a surfeit of nutrients, and is one of the most important pro-aging conditions in the developed world; it shortens lifespan by significantly increasing the risk of type II diabetes, cardiovascular disease, Alzheimer’s disease, and numerous cancers.  In aggregate, these diseases account for the vast majority of deaths in most nations worldwide.

What are the biological mechanisms linking nutrient status and metabolism to this plethora of devastating diseases?

To address this question, we largely focus our scientific efforts on mitochondria for two main reasons.  First, mitochondria metabolize the vast majority of nutrients that we consume.  Second, mitochondrial dysfunction is strongly implicated in virtually every age-related disease.  The approaches we use include a combination of genetics, molecular biology, ‘omics screens, and biochemical techniques in cells and genetically modified animals.   Some examples of research projects we are currently or soon to be working on include the following:

  1. The role of uncouplers of oxidative phosphorylation (e.g. uncoupling proteins, UCP1-5) in the regulation of skeletal muscle and adipose tissue metabolism, and in obesity and type II diabetes development / prevention.
  2. The identification of the signals and cytoplasmic sensors that link mitochondrial metabolic changes to cell differentiation, growth and tumor development.
  3. The use of the C. elegans nematode as a genetic model system to understand the role of novel mitochondrial metabolic regulatory proteins in aging and metabolic physiology.
  4. The development of drugs to stimulate metabolic fuel disposal as an anti-obesity and anti-aging pharmacologic strategy.
  5. The mechanisms regulating the efficiency of mitochondrial oxidative phosphorylation.