Food restriction (FR) is the most effective experimental manipulation known that retards aging and disease processes in laboratory rodents. However, the molecular mechanisms responsible for this extended life span are poorly understood. It is widely accepted that the mechanism of action of FR involves changes in gene expression. However, the chain of molecular events linking the initial perception of reduced food availability to the altered expression of genes that ultimately retard aging is not known. The goal of this proposal is to identify gene products involved in the initial links of that chain. The focus will be on the hypothalamus and anterior pituitary where the initial perception of and response to reduced food availability is likely to occur. The objective of the proposed study is to identify differentially expressed genes in the hypothalamus and anterior pituitary that are activated/repressed immediately after the onset of FR, are maintained at the altered levels throughout the FR period, and are reversed by returning the add libitum (AL) diet. This objective will be accomplished by the three following aims: 1. To identify genes in the hypothalamus and the anterior pituitary whose expression is altered by FR in 3 month old rats. 2. To identify those clones obtained in Specific Aim 1 whose altered expression occurs rapidly after the onset of FR, is sustained throughout the duration of FR, and is reversed by AL diet. 3. To characterize the genes that are identified in Specific Aim 2. The results generated from these studies and the research skills obtained through this award combined with a rich environment of biogerontological expertise will provide a strong foundation for the candidate to develop an independent research program melding molecular biological approaches in a physiological context to make substantive contributions to the basic biology of aging.
|Fu, Chunxiao; Hickey, Morgen; Morrison, Melissa et al. (2006) Tissue specific and non-specific changes in gene expression by aging and by early stage CR. Mech Ageing Dev 127:905-16|