Metabolic Biochemistry of the Mediterranean Diet Association with Longevity

The typical Mediterranean diet has long been associated with cardiovascular health, suppression of obesity and type 2 diabetes, and longevity. One of the major components of the Mediterranean diet is olive oil. Olive oil is enriched in triglycerides containing the monounsaturated fatty acid (MUFA), oleic acid.

Oleic acid (18:1) is the most abundant MUFA in the human body. Palmitoleic acid (16:1) is also an abundant MUFA in human cells. These two fatty acids represent the majority of MUFA present in membrane phospholipids, triglycerides, and cholesterol esters. The health benefits of oleic acid are broad and profound. Numerous studies have shown that consumption of MUFA, particularly oleic acid, is important to maintain low levels of low density lipoproteins (LDL; the so-called bad cholesterol) in the blood and is also likely to be associated with the potential for elevated high density lipoproteins (HDL; the so-called good cholesterol). Another physiologically significant effect of oleic acid is the result of its conversion to oleoylethanolamide (OEA) in the small intestine. OEA has demonstrated effects in the central nervous system (CNS) related to the control of appetite and feeding behaviors.

A recent paper in the journal, Nature Cell Biology, demonstrates that the mechanism by which MUFA contribute to longevity involves an organelle network of lipid droplets and peroxisomes:

Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids

Granted this work was carried out in the round worm, Caenorhabditis elegans, the potential implications for human health and longevity are intriguing.

Lipid droplets within cells are considered organelles and they are critical to overall fat storage and metabolism. What was uncovered in this research was that as the level of MUFA increases, so too does the overall number of lipid droplets. When the levels of enzymes involved in MUFA metabolism were altered in C. elegans there was a correlation to longevity. Increasing the level of stearoyl-CoA desaturase (SCD), the enzyme that generates oleic acid, was associated with increased longevity. If the levels of enzymes that metabolize MUFA were decreased longevity was also seen to increase.

Supplementation of the C. elegans diet with MUFA was shown to increase the number of lipid droplets in cells and the number of lipid droplets was found to correlate to longevity. The enzyme, phosphatidic acid phosphatase 1 (PAP1), which is involved in the synthesis of triglycerides, is encoded by the LPIN1 gene. Interference with LPIN1 expression leads to lower MUFA levels in triglycerides and fewer lipid droplets. This is also associated with decreased longevity.

One major contributors to aging is lipid peroxidation. Indeed, it has been demonstrated that the level of lipid oxidation products is higher in older humans when compared to younger humans. Increased levels of MUFA, particularly levels of oleic acid, have been shown to reduce lipid oxidation products in middle aged humans. The role that MUFA play in the reduction of lipid oxidation is through stimulating increases the production of lipid droplets.

The organelles known as peroxisomes are responsible for the metabolism of numerous types of lipid molecules including di- and trihydroxycholestanoic acids (DHCA and THCA; bile acid intermediates); long-chain dicarboxylic acids that are produced by ω-oxidation of long-chain monocarboxylic acids; pristanic acid via the α-oxidation pathway; certain polyunsaturated fatty acids (PUFA) such as tetracosahexaenoic acid (24:6), which by β-oxidation yields the important PUFA docosahexaenoic acid (DHA); and certain prostaglandins and leukotrienes. MUFA accumulation was found to result in increased peroxisomes which was correlated to increased longevity similar to the effects of MUFA on lipid droplet dynamics.

TAKE HOME: Whereas the health and longevity benefits of a typical Mediterranean diet have been appreciated for many years work is now being carried out to determine the precise biochemical mechanism that underlie these dietary phenomena. The future benefits of this type of research may very well be targeted therapies that alter the metabolism of MUFA to promote health and longevity.