Dolichol, an end product of the mevalonate pathway, has been proposed as a biomarker of aging, but its biological role, not to mention its catabolism, has not been fully understood. UV‐B radiation was used to induce oxidative stress in isolated rat hepatocytes by the collagenase method. Effects on dolichol, phospholipid‐bound polyunsaturated fatty acids (PL‐PUFA) and known lipid soluble antioxidants [coenzyme Q (CoQ) and α‐tocopherol] were studied. The increase in oxidative stress was detected by a probe sensitive to reactive oxygen species (ROS). Peroxidation of lipids was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). Dolichol, CoQ, and α‐tocopherol were assessed by high‐pressure liquid chromatography (HPLC), PL‐PUFA by gas–liquid chromatography (GC). UV‐B radiation caused an immediate increase in ROS as well as lipid peroxidation and a simultaneous decrease in the levels of dolichol and lipid soluble antioxidants. Decrease in dolichol paralleled changes in CoQ levels and was smaller to that in α‐tocopherol. The addition of mevinolin, a competitive inhibitor of the enzyme 3‐hydroxy‐3‐methylglutaryl CoA reductase (HMG‐CoAR), magnified the loss of dolichol and was associated with an increase in TBARS production. Changes in PL‐PUFA were minor. These findings highlight that oxidative stress has very early and similar effects on dolichol and lipid soluble antioxidants. Lower levels of dolichol are associated with enhanced peroxidation of lipids, which suggest that dolichol may have a protective role in the antioxidant machinery of cell membranes and perhaps be a key to understanding some adverse effects of statin therapy.

Aging has been defined as a gradually decreasing ability to maintain homeostasis and increasing risk to die. Growing evidence supports malfunctioning with age of quality control system. At an older age, accumulation of altered macromolecules and membranes may impair cell functioning; accumulation of altered mitochondria and peroxisomes may boost the yield of ROS per unit of produced energy and accelerate the aging process. Evidence produced that autophagy, an essential part in cell housekeeping during fasting, may help removal of altered membranes, mitochondria and peroxisomes selectively and account for the antiaging effects of caloric restriction. Stimulation of autophagy may improve innate and adaptive immunity; decrease the risk of myopathy, heart disease, liver disease, neurodegeneration and cancer; and retard aging. Functioning of autophagy may decline in well fed adults and is almost negligible at older age. Induction of autophagy may result in “cleaner cells” lower in oxidative status and more resistant to injury and disease. The administration of antilipolytic drugs to fasted animals was shown to intensify autophagy in a physiologically appropriate manner, to enhance submaximal antiaging effects of low level of caloric restriction, to rapidly rescue older cells from the accumulation of altered mtDNA and older peroxisomes, to increase urinary 8-OHdG levels, and counteract the age-related hypercholesterolemia in rodents. In conclusion, benefits of long-lasting stimulation of autophagy and protein and organelle turnover shows that antilipolytic drugs might find a novel therapeutic application in antiaging medicine.