There’s a new threat to our cells…

Healthy Aging

…but we have a hypothesis that may protect them

In this Whole Body Health Series, we are sharing the latest science on our whole body, from our cells on up.

In our last issue, we talked about the rising importance of strong cells. This week, we’re continuing our coverage of a new threat to our cellular health. It’s called ferroptosis.

Well, that sounds ominous. What exactly is ferroptosis, again?

As we shared last week, ferroptosis is a newly found way that our cells are dying. This process was discovered by a research team at Columbia University back in 2012.

As described by Dixon et al., ferroptosis involves three basic steps:

• Step 1:  Fragile cell membranes. Ferroptosis starts when fragile fatty acids (aka polyunsaturated fatty acids) in our cell membranes incite lipid peroxidation.
• Step 2: Lipid peroxidation + intracellular iron. Lipid peroxidation then combines with unwanted iron inside our cells to induce high levels of reactive oxygen species (ROS).
• Step 3: Reactive oxygen species (ROS) that attack mitochondria. In turn, ROS knocks out our cells’ powerhouses (aka our mitochondria)… and our cells altogether.

The result? Thousands of studies have shown that ferroptosis is an emerging problem that negatively impacts our metabolic, heart and liver health.

Wait, how is iron involved in ferroptosis?

For our fellow nerds, you probably already picked up that “ferro” in ferroptosis stands for “iron”. While we are used to hearing about the need to fix iron deficiencies, iron also has a naughty side when it is running free and gets into our cells.

In fact, there is a name for renegade iron in our bodies. It’s called dysmetabolic iron overload syndrome (or DIOS). As described by Sachinidis et al., DIOS is directly linked to poor metabolic, heart and liver health. While DIOS used to be rare, Deugnier et al. share that this condition has been on the rise globally, right along with ferroptosis.

I think I understand, but how does “bad” iron get into our cells in the first place?

There are many hypotheses, but the following pathway has gained traction, including from our own discoveries while caring for older dolphins with DIOS and impressive insights from Otogawa et al.

• Red blood cells become more fragile due to unstable cell membranes.
• These weak red blood cells are engulfed by cells in the liver, called Kupffer cells.
• Red blood cell corpses leave behind iron deposits in our liver, which impair liver function.
• When enough iron accumulates in the liver, this excess iron spills over into the bloodstream and other organs.

Over time, the combination of fragile cells with excess iron can lead to ferroptosis.

Detecting the precursors of ferroptosis.

Given all the above, there are tests that can detect various precursors and components of DIOS and ferroptosis, including the following:

Red Blood Cell Fragility Tests 

• The Osmotic Fragility Test directly measures the strength of our red blood cells.
• The Saturation (aka Stability) Index measures the ratio of selected unstable versus stable fatty acids in red blood cell membranes.
• Hemoglobin measures normal or low amounts of functioning red blood cells. Low hemoglobin can occur if red blood cell loss (including due to fragility) is higher than new red blood cell production.
• Red Blood Cell Distribution Width (RDW) measures the variability of red blood cell sizes. A high RDW may indicate premature loss of fragile red blood cells.

Lipid Peroxidation & Iron Overload Tests

• Lipid Peroxidation levels measure the amount of lipid peroxidation in blood or urine.
• Ferritin measurements can help detect potential iron overload in tissues, including the liver.

It is important to note that none of these tests are specific for DIOS and ferroptosis. As such, you need to work with your doctor to help guide which tests are appropriate and how to interpret the results.