The adrenal cortex is known to be a major site for lipofuscin accumulation in aging animals and humans. The relationship between the formation of lipofuscin and adrenocortical steroidogenesis has not been elucidated. This proposal is designed to determine how aging effects on lipid metabolism may be related to the genesis of lipofuscin and the steroidogenic capacity of the rat adrenal cortex. Four experimental designs have been proposed to: 1. Study the adrenocortical lipid contents of mature (12-14 months) and aging (24-26 months) rats and relate them to steroidogenic activity. 2. Determine the level of ACTH-dependent lipid synthesis in the adrenal cortex of these two groups of rats. 3. Determine the level of lipofuscin-containing fluorescent substances in adrenal cortex at different ages. 4. Investigate whether the levels of these fluorescent substances are altered by ACTH stimulation of the animals during a defined period of time. These experiments will be directed by Dr. Behling Cheng, who has recently completed his post-doctoral training in the laboratory of Dr. Jerome Kowal. Dr. Cheng received his Ph.D. in the laboratory of Dr. Tokuji Kimura for studies of lipid and cholesterol metabolism in adrenal cells. The work will be carried in Dr. Kowal's laboratory. The results of these experiments should provide important new information on whether the basal and hormone-stimulated levels of adrenocortical lipids are influenced by aging, and how these changes in lipid metabolism are related to the formation of lipofuscin in adrenocortical cells. These studies could provide a model for further analyses of these types, not only in adrenal cells, but in other tissues whose functions may be affected by alterations in lipid metabolism and content during senescence.
| Cheng, B; Horst, I A; Mader, S L et al. (1990) Diminished adrenal steroidogenic activity in aging rats: new evidence from adrenal cells cultured from young and aged normal and hypoxic animals. Mol Cell Endocrinol 73:R7-12 |
