Age-dependent accumulation of dolichol in rat liver: is tissue dolichol a biomarker of aging?
Dolichols are long hydrophobic molecules broadly distributed in all tissues and cellular membranes of eukariotic cells. Dolichol affects membrane structure and fluidity, membrane-associated protein activities, and membrane sensitivity to oxidative stress. Reports have 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 humans. In our longitudinal study, the age-related accumulation of dolichol was monitored in the liver tissue of male Sprague Dawley rats fed ad libitum up to age of 27 months. In addition 24-month-old rats subjected to different regimens of anti-aging diet restriction (40% calorie restriction or every-other-day feeding ad libitum) were tested. A parallel study of the accumulation of carbonyl in liver protein (a proposed biomarker of aging) was made. In addition, the age-related decline of liver autophagy/proteolysis was studied in isolated liver cells, in view of the essential role of this function in liver membrane maintenance. Results show that an age-dependent accumulation of dolichol can be observed in the liver of the rats fed ad libitum but not in the liver 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 concluded that dolichol accumulation satisfies the proposed primary and secondary applicable criteria and the desirable features required to be qualified as a biomarker of aging.
Marino
M
M
Dipartimento di Biologia, III Università di Rome, Italy.
Dolfi
C
C
Paradiso
C
C
Cavallini
G
G
Masini
M
M
Gori
Z
Z
Pollera
M
M
Trentalance
A
A
Bergamini
E
E
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002784:Cholesterol / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004286:Dolichols / Q000378:metabolism*; D005508:Food Deprivation / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000378:metabolism
D015415:Biomarkers; D004286:Dolichols; D002784:Cholesterol; D014633:Valine