Ageing and oxidative stress: A role for dolichol in the antioxidant machinery of cell membranes?

Abstract

Dolichol is a polyprenol compound broadly distributed in membranes, biosynthetized by the general isoprenoid pathway from acetate via mevalonate and farnesyl pyrophosphate. Dolichol lays inside the membrane between the two leaflets of the lipid bilayer very close to the tail of phospholipid fatty acids. No definite catabolic pathways for this molecule have yet been identified. Evidence is produced that dolichol levels increase dramatically with increasing age; that anti-ageing caloric restriction retards this age-associated change; that dolichol may act as a radical scavenger of peroxidized lipids belonging to the cell membranes. In view of the polyunsaturated fatty acids (PUFA), dolichol and Vitamin E location and stechiometry, it is proposed that molecules might interact each-other to form a highly matched free-radical-transfer chain, whose malfunctioning might be involved in statin toxicity and neurodegenerative diseases.

p53, Oxidative Stress, and Aging

“…ROS production and a decreased antioxidant capacity are thought to contribute to the aging process by oxidative modification of different macromolecules, such as lipids, proteins, and genomic DNA (12,20,25,62,63,65,96,109,117).…”

Autophagy and Aging: The Importance of Maintaining "Clean" Cells

“…2,3 Accumulation of damaged (e.g., oxidized and/or glycated, i.e., nonenzymatically glycosylated) extracellular, intracellular and membrane proteins may account for the age-associated malfunctioning of many biological processes and has been frequently used as a biomarker of aging. 3 For example, accumulation of damaged 3-hydroxy-3-methylglutaryl coenzyme A reductase in the endoplasmic reticulum may cause hypercholesterolemia 4 and an abnormal increase in the tissue levels of the lipid-soluble anti-oxidant dolichol, 5 which is an excellent biomarker of aging. 6 Similarly, accumulation of oxidized nuclear 7 and mitochondrial DNA 8 (mtDNA) and of damaged organelles (in particular, mitochondria and peroxisomes) may start a vicious circle perpetuating the age-related increase in oxidative stress.…”

Changes in dolichol and pentosidine levels in the age-mismatched heterotopically transplanted rat heart

“…These results confirm that the transfer of dolichol from and to tissues and/or from the peripheral tissues to the liver via circulation is negligible (Elmberger et al 1987); and provide evidence that accumulation of dolichol in older tissues is a primary effect of aging, may be the consequence of an alteration of dolichol metabolism in those tissues or a defence attempt against an increased an increased free radical attack. Indeed it was hypothesized that the age-related changes in dolichol levels might reflect an aging-related derangement of free radical metabolism in cell membranes (Bergamini et al 2004), possibly associated with a larger peroxidation of membrane proteins and an alteration in transmembrane signalling (Cavallini et al 2001;Bergamini and Gori 1995;and unpublished). If this is the case, the age-associated cell-membrane defect(s) in free-radical metabolism should be resistant to organ transplantation.…”