Recent studies from our laboratory showed that dolichol accumulates in aging human and mouse brain and it is especially concentrated in lipofuscin. The objective of the proposed study is to determine whether dolichol accumulation occurs in tissues other than brain and to find the biochemical mechanism that leads to its storage in aging. Since dolichol synthesis is expected to be low in aging brain, a catabolic defect is suggested to explain dolichol storage in aging. Nothing is known about the catabolism of dolichol. Appropriately labeled dolichol will be used to study the normal catabolism of dolichol in young adults and in aging mouse brain by both in vivo and in vitro experiments. Preliminary studies suggest that an alcohol dehydrogenase related enzyme may be involved in the initial steps of the oxidation of dolichol. Effect of a lipofuscin lowering drug (centerophenoxine) in aging mouse, on dolichol metabolism will also be investigated. Attempts will be made to isolate and identify the autofluorescent component in lipofuscin.
| Morris, G N; Pullarkat, R K (1991) Dolichol levels during development and ageing of Drosophila melanogaster. Comp Biochem Physiol B 98:267-9 |
| Pullarkat, R K; Pullarkat, P S; Morris, G N (1990) Phosphorylated dolichols in aging. Biochem J 265:891-4 |
