Aging of the brain decreases cognitive and motor abilities and leads to morphological and functional changes of certain populations of neurons. These changes increase risk towards neurodegenerative diseases such as Parkinson’s or Alzheimer’s disease and are believed to contribute to neurodegeneration and aging.
Aging is the major risk factor for the development of neurodegenerative disorders. To date, only few studies have addressed the molecular and biochemical mechanisms underlying aging in postmitotic differentiated neurons. Research of aging has focused on model systems (yeast, round worm, fruit fly) and proliferating cells (replicative senescent). Impairment in protein turnover, calcium metabolism, increased production of reactive oxidative species, and instability of mitochondrial and nuclear genome are some of the changes that have been characterized. Using a newly established in vitro model of aged, differentiated, postmitotic neurons we will study the transcriptional regulation of aging by DNA microarrays. In addition we will study the transcriptional regulation of aging in different brain areas. Subsequently we will study the functional role of the regulated transcripts in the aging process. These studies will lead to a new understanding of the mechanisms underlying aging and neurodegenerative disorders.