Iron overload drives aging

Healthy Aging

Iron is essential, but it has a dark side (especially as we age)

In this series, we are covering the science behind our cell membranes – because they literally cover our cells, our health, and even our longevity.

Last week, we discussed fatty acids – including C15:0 – that help cells survive in extreme environments. This week, let’s talk about a newly recognized phenomenon that shortens our cells’ survival.

What shortens cell survival? Hint: It’s a bit iron-ic

When we talk about iron and our health, most of us think “iron deficiency”. Over the past decade, however, scientists have shown that iron metabolism is much more complicated than we once thought. In fact, as reviewed by Rochette et al., excess free iron is now recognized as a major driver of cellular breakdown.

The word of the week is ferroptosis

Apoptosis is defined as the normal death of cells. When cells are damaged beyond repair, they need to be recycled out: this is apoptosis.

In contrast, ferroptosis is a phenomenon in which iron prematurely kills cells. As described by Rochette et al., iron requires an accomplice to take out our cells – namely, polyunsaturated fatty acids (PUFAs) in our cell membranes. When free iron meets fragile PUFAs, the result is a vicious cycle of lipid peroxidation, inflammation, and early cell death.

Wait, I thought iron was good for me.

Indeed, iron is an essential mineral that helps to keep our red blood cells healthy. In a paper titled “Role of iron in aging related diseases,” however, Chen et al. describe how iron accumulates in our tissues as we get older, contributing to the onset or worsening of:

• Arthritis
• Liver cirrhosis
• Heart disease
• Neurodegenerative diseases
• Cancer
• Diabetes
• Anemia

This condition is called “iron overload”. While iron overload was initially recognized as primarily a genetic disorder, Deugnier et al. found that a rising number of cases of iron overload are unexplained – and associated with the rise in metabolic diseases. Thus, they called this phenomenon dysmetabolic iron overload syndrome (aka, DIOS).

Are there treatments for iron overload?

Well, leeches. Or to get less medieval, clinical blood draws successfully pull iron from our tissues to treat iron overload. Alexandros et al. review the ongoing debate, however, regarding the benefits and risks of blood letting. Unfortunately, removing blood is a temporary treatment that does not address the underlying cause of iron overload. As such, it must be repeated routinely.

Iron chelators, which bind to free iron to remove excess amounts from the body, is another option. Entezari et al. summarize the advantages and disadvantages of the leading FDA-approved iron chelators, deferoxamine, deferiprone, and deferasirox. Like blood draws, however, iron chelators do not address the underlying causes of iron overload.