Anorexia in the elderly - a hiring and wiring problem in the hypothalamus

The elderly often develop poor appetite (anorexia) and their reduced calorie and nutrient intake worsens the effects of aging in multiple tissues. Hunger and level of energy-expenditure are controlled by a discrete population of neurons in an area of the brain called hypothalamus. Broadly, these neurons occur as two different subtypes and work in a 'tug of war' manner to induce state of hunger versus fullness. In this project, the student will ask whether ageing-related anorexia is due to a progressive decline in the number and/or functioning of specific subset of these neurons. Using a powerful set of transgenic reporter mice, the student will accurately measure and compare these changes in the brain of young, middle-aged and heavily aged mice. To gain insight into molecular changes, the student will also examine changes in hypothalamic genes that are differentially turned on or off, or are reduced or elevated with ageing. In a complementary strand, the student will ask whether there is a reduced supply of new neurons to circuits that control appetite, by a newly-discovered population of hypothalamic neural stem/progenitor cells, called tanycytes. Moreover, the student will test whether genetic knockdown or over-expression of certain genes expressed by tanycytes can enhance or reduce hypothalamic neurogenesis in the aged brain as means of counteracting neuronal loss in this region.