Chronic caloric restriction (CR) has been demonstrated to increase longevity in lower species and studies are ongoing to evaluate its effect in higher species. A consistent metabolic feature of CR is improved insulin sensitivity and lowered lifetime glycemia, yet the mechanism responsible is currently unknown. However, the membrane's physiochemical properties, as determined by phospholipid composition, have been related to insulin action in animal and human studies and CR has been reported to alter membrane lipid content.
Hardly an aspect of aging is more important than an organism's ability to withstand stress or to resist both internally and externally imposed insults. We know that as organisms loose their ability to resist these insults, aged organisms suffer more than the young. Therefore, a prime strategy for an organism's survival has been the evolutionarily adapted defense systems that guard against insult. For better survivability, an organism's defense system must be maximized to its full effect through well-coordinated networks of diverse biologically responsive elements.
Nonenzymatic molecular modifications induced by reactive carbonyl species (RCS) generated by peroxidation of membrane phospholipids acyl chains play a causal role in the aging process. Most of the biological effects of RCS, mainly alpha,beta-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to their capacity to react with cellular constituents, forming advanced lipoxidation end-products (ALEs). Compared to reactive oxygen and nitrogen species, lipid-derived RCS are stable and can diffuse within or even escape from the cell and attack targets far from the site of formation.
Although general anesthetics were first used more than 160 years ago, their mechanisms have remained mysterious. During the past decade, significant progress in our understanding of general anesthetic action at the cellular and network system levels has been made.
N-3 polyunsaturated fatty acids (PUFAs) from fish oil exert their functional effects by targeting multiple mechanisms. One mechanism to emerge in the past decade is the ability of n-3 PUFA acyl chains to perturb the molecular organization of plasma membrane sphingolipid/cholesterol-enriched lipid raft domains. These domains are nanometer-scale assemblies that coalesce to compartmentalize select proteins for optimal function. Here we review recent evidence on how n-3 PUFAs modify lipid rafts from biophysical and biochemical experiments from several different model systems.