Experiment Reveals How The Mediterranean Diet Works At The Cellular Level

The Mediterranean diet has become famous far beyond its namesake sea, as research increasingly supports its longstanding reputation for boosting health and longevity.

Studies have shown that people on the Mediterranean diet – which emphasizes plant-based foods and fish, and not so much red meat or dairy – tend to be healthier in multiple ways, with lower rates of heart disease, cancer, diabetes, dementia, and overall mortality.

But why? Despite strong evidence for health benefits, it remains unclear how exactly this mix of foods, at the cellular level, can lengthen lifespan.

That may be changing, though. A study led by researchers from Stanford University in the US has revealed cellular effects of the Mediterranean diet for the first time, based on how one of its healthy fats influenced lifespan in nematodes, also known as roundworms.

Finding this link is a big deal, the study's authors say, offering new insights on the health effects of various fats and the role diet plays in longevity.

"Fats are generally thought to be detrimental to health," says Stanford University geneticist Anne Brunet. "But some studies have shown that specific types of fats, or lipids, can be beneficial."

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The Mediterranean diet abounds with beneficial fats, also known as monounsaturated fatty acids (MUFAs), found in foods like nuts, fish, and olive oil. The new study focused on one healthy fat, oleic acid, which is the main MUFA in olive oil and some nuts.

Using the roundworm Caenorhabditis elegans, Brunet and her colleagues discovered two benefits of oleic acid: It protects cell membranes from damage by lipid oxidation, and it raises the quantity of two key cellular components called organelles.

Those effects make a significant difference, the researchers report, with roundworms fed oleic acid living about 35 percent longer than worms on a more traditional diet.

One type of organelle, a fat reservoir called a lipid droplet, let the researchers predict with surprising accuracy how many days a worm would survive.

"The number of lipid droplets in individual worms tells me that animal's remaining lifespan," says Stanford University biochemist Katharina Papsdorf. "The worms with greater numbers of lipid droplets live longer than those with fewer droplets."

The roundworms ate bacteria supplemented with either oleic acid or elaidic acid, a monounsaturated trans fatty acid found in margarine and fried foods. The two acids have similar molecular structures but very different health effects.

Trans fats like elaidic acid are considered unhealthy or "bad" fats, since they increase the risk of heart disease, dementia, and other health problems.

"We saw that the numbers of lipid droplets in the worms' intestinal cells increased if the worms were exposed to oleic acid, and that this correlated with an extension of lifespan," Brunet says.

Exposure to elaidic acid, on the other hand, didn't increase the number of lipid droplets or the number of days the worms lived.

Lipid droplets are important for cellular metabolism, the researchers note, helping regulate the usage of fat supplies as cells' energy. When researchers blocked a gene for proteins that help roundworm cells make lipid droplets, the life-extending effect disappeared.

On top of the increase in lipid droplets, roundworms' intestinal cells also had more organelles called peroxisomes, which contain enzymes involved in oxidation and metabolism.

Lipid droplets and peroxisomes were more abundant in cells of younger animals, the researchers report, naturally dwindling with age.

The number of these organelles also varies among individuals, and worms who naturally have more in their cells also tend to live longer, showing an effect similar to worms fed oleic acid.

Along with its effects on organelles, oleic acid protected cells by limiting lipid oxidation, a chemical reaction that damages cell membranes. Elaidic acid had the opposite effect, increasing oxidation at the expense of cellular integrity.

"Membrane oxidation is very bad news for an organism," Brunet says. "Cell membranes can begin to leak and fail, which can cause a cascade of adverse biological effects."

These are major insights into the links between diet and longevity, the researchers write, revealing key details about how specific components of the Mediterranean diet can extend lifespan.

That could improve dietary guidelines, and it might eventually inspire ways to combat effects of aging by mimicking oleic acid's defense against oxidation.

For now, though, the researchers note this is an intriguing discovery that warrants more research, including studies of whether and how these findings apply to humans.

"For years, we've been very interested in learning how diet influences lifespan," Brunet says. "It will be fascinating to see whether we see a similar association between lipid droplets and longevity in mammals and humans. These findings suggest there may be a fat-based strategy to improve human health and longevity."

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