C Dolfi

The age-related accumulation of dolichol in rat liver may correlate with expectation of life

In order to test the hypothesis that the ageing-related alteration in membrane lipids might reflect the biological age of rodents, the levels of liver dolichol were assayed by the HPLC procedure in male ad-libitum fed (AL) Sprague-Dawley rats aged 2, 6, 12 and 24months, and in 24-month-old rats on anti-aging food-restrictions (FR) differing in duration and in their effects on longevity. Results showed that the effects on liver dolichol of FR initiated at 2, 6 and 12 months of age, or initiated at 2 and interrupted at 18 months of age were significantly different, and reflected the differences in the effects of FR on expectation of life (the longer the expected residual lifespan the lower the content in liver dolichol). The conclusion is that assay of the quantity of dolichol in the liver tissue may be used as a marker of the biological age of the animal and therefore as an important biomarker of ageing.

Effects of ageing and increased haemolysis on the levels of dolichol in rat spleen.

Dolichol is a long-chain polyisoprenoid. No enzyme pathway for dolichol degradation was discovered. Dolichol accumulates in human and rodent tissues during ageing. Red blood cells contain a larger amount of dolichol and red blood cell life span is shorter in older rats. The effects of age and of the load of dolichol from red blood cell degradation on the ageing-associated accumulation of dolichol in spleen were studied in 2, 6, 12, 18 and 24 month-old male Sprague Dawley rats fed ad libitum (AL) or on an anti-ageing dietary regimen (EOD). Tissue dolichol was extracted and assayed by HPLC [J. Gerontol. 53A (1998) B87]. Levels of dolichol increased in spleen, liver, kidney and muscle in parallel fashion from the age of 2 to 12 months. Unexpectedly, spleen dolichol decreased in older rats whereas liver, kidney and muscle dolichol increased significantly. The effects of haemolysis on spleen dolichol were tested by the administration of phenylhydrazine. Results show that haemolysis does not increase, but rather decreases the levels of dolichol in erythroclastic organs. It is concluded that the levels of spleen dolichol may decrease in the absence of any known enzymatic degradative pathway if the spleen and its resident phagocytes are forced to cope with a higher number of red blood cells to be cleared. Free-radical mediated decomposition of dolichol by phagocytic cells during erythrophagocytosis might be involved in the process.

Effect of increasing age on tissue dolichol levels in ad libitum fed and food-restricted rats

In order to test the hypothesis that the ageing-related alteration in membrane lipids might reflect the biological age of rodents, we studied the effects of age in ad libitum fed (AL)and food-restricted (FR) male Sprague-Dawley rats on the levels of dolichol in different organs involved [liver (L) and kidney (K)] or not involved [brain (B), sciatic nerve (SN),heart (H), soleus (S) and extensor digitorum longus (EDL) muscles] in dolichol excretion. At the given age, tissue dolichol was extracted and assayed by HPLC procedure. Results show that the levels of dolichol were significantly different in different tissues and increased dramatically with increasing age. The anti-ageing FR regimen had significant preventive effects on dolichol accumulation in the excretory organs. The effect of FR on the liver was much bigger than that of kidney. The effect of FR retarding dolichol accumulation in the liver co-varied with the effects of FR on longevity. In conclusion, these data show that the quantity of dolichol in the hepatic tissue might be used as a marker of the biological age of the animal.