AGE-DEPENDENT ACCUMULATION OF DOLICHOL IN RAT-LIVER - IS TISSUE DOLICHOL A BIOMARKER OF AGING

Dolichols are long hydrophobic molecules broadly distributed in all ti ssues and cellular membranes of eukariotic cells. Dolichol affects mem brane structure and fluidity, membrane-associated protein activities, and membrane sensitivity to oxidative stress. Reports Rave shown that dolichols exhibit a remarkable (6- to 30-fold) age-related increase in the tissues of adult and mature rats and of old flies, mice, and huma ns. III our longitudinal study, the age-related accumulation of dolich ol Has monitored in the liver tissue of male Sprague Dawley rats fed a d libitum up to age of 27 months. In addition 24-month-old rats subjec ted to different regimens of anti-aging diet restriction (40% calorie restriction or every-other-day feeding ad libitum) were tested. A para llel study of the accumulation of carbonyl in liver protein (a propose d biomarker of aging) was made. In addition, the age-related decline o f liver autophagy/proteolysis was studied in isolated liver cells, in view of die essential role of this function in liver membrane maintena nce. Results show that an age-dependent accumulation of dolichol can b e observed in the liver of the rats fed ad libitum but not in the live r of 24-month-old food-restricted rats, that accumulation of dolichol precedes the accumulation of altered liver proteins, and that dolichol accumulation is accompanied by a decline in liver autophagy. It is co ncluded that dolichol accumulation satisfies the proposed primary and secondary applicable criteria and die desirable features required to b e qualified as a biomarker of aging.