The Bonasera laboratory is interested in how the brain normally ages. As the brain ages, doctors, scientists, and family members can see changes in behaviors that are important for a loved one to remain independent and at home. These behaviors include physical activity and walking, eating, drinking, resting, and socializing. Many investigators combine how people perform these behaviors into a single, broad measurement called "Lifespace." However, doctors and scientists currently use very simple methods to determine lifespace. These methods provide only a snapshot of a Lifespace at a given time, and are not very sensitive to significant changes in Lifespace size. We study lifespace in mouse models of aging, and in translational clinical studies of human aging. In cohorts of young, middle-aged, and aged mice, we have developed equipment to precisely measure feeding, drinking, movement, and how these behaviors occur on a day to day basis. We then study age-related changes in gene expression in different regions of the brain to determine possible factors influencing age-related changes in these important "functional" behaviors. We have shown that age-related decreases in mouse food and water intake correlate with:
- dysregulation of immune/defense gene expression within the hypothalamus, and
- with an overall dysregulation of how gene expression is synchronized within cells. To translate this approach to ambulatory human populations, our group has used mobile phones to collect data describing an individual's total activity, in-home location, and in-community location on a continuous basis. This approach to studying lifespace is inexpensive, non-invasive, temporally and spatially precise, and highly valid. Thus, we are in an ideal position to identify specific pharmacological or therapeutic interventions to preserve an individual's functional behavior, quickly test these interventions in large groups of mice, and then evaluate human clinical populations for identical measures. In this way, we hope to find specific treatments that will maximize people's independence and functional capacity with aging.
Sixty-four station mouse home cage monitoring system with associated workstations for data quality control, classification, and analysis; 4 station rodent indirect calorimetry measurement system with integrated activity monitoring; standard behavioral phenotyping equipment including 4 chamber open field, elevated zero maze, Noldus Observer and EthoVision acquisition and analysis software; RNA purification and quantification workflow, including Qiagen TissueLyser II, Qiagen Qiacube, Thermo Nanodropper II, Agilent BioAnalyzer 2100, Eppendorf ep RealPlex RT-qPCR; Nokia N79-based cell phone data acquisition system with appropriate server software for highly secured data transmission; standard laboratory equipment (centrifuges, -80 freezer capacity, -20 freezer capacity, refrigerator capacity, electronic balances to manage milligram to gram samples, pH meter, incubators, water baths, standard molecular biology tools).