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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG004244-02
Application #
3115032
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Institute for Basic Research in Dev Disabil
Department
Type
DUNS #
167205090
City
Staten Island
State
NY
Country
United States
Zip Code
10314
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