Ferroptosis is a form of regulated cell death that is distinct from apoptosis or necrosis. It is characterized by the accumulation of iron-dependent lipid peroxides, which damage cell membranes and lead to cell collapse.
Discovered in the last decade, ferroptosis has quickly become a significant area of study in aging, neurodegeneration and cancer research. Because it is tied to both oxidative stress and iron metabolism, two critical elements of cellular health, it is particularly relevant in understanding how cells deteriorate or survive under stress.
Unlike apoptosis, which is programmed and orderly, ferroptosis results from unchecked oxidative damage, especially in the presence of excess intracellular iron. This makes it not only a marker of cellular fragility but also a potential therapeutic target in diseases where either too much or too little cell death is a problem.
How it works
At the core of ferroptosis is the imbalance between oxidative stress and the cell’s ability to detoxify reactive species. Cells rely on an enzyme called GPX4 (glutathione peroxidase 4) to neutralize lipid peroxides. When GPX4 is inhibited or when glutathione (an antioxidant) is depleted, lipid peroxides build up. If there is enough free iron (Fe²⁺)available, it participates in reactions (such as the Fenton reaction) that generate highly reactive radicals, accelerating lipid oxidation and pushing the cell toward ferroptosis.
This process affects cells with high iron content or weak antioxidant defenses, such as neurons, liver cells and certain cancer cells.
Ferroptosis and disease
Researchers are studying ferroptosis in a variety of contexts. In neurodegenerative diseases like Alzheimer’s and Parkinson’s, cells often accumulate both iron and oxidative stress, conditions that promote it and contribute to neuronal loss. In cancer therapy, by contrast, some strategies aim to induce ferroptosis selectively in tumor cells to eliminate them when they resist other forms of cell death.
Ferroptosis has also been linked to ischemia-reperfusion injury, a type of damage that occurs when blood supply returns to tissue after a period of oxygen deprivation. In this scenario, a sudden burst of oxidative stress combined with available iron makes it a major driver of cell death.
Ferroptosis and aging
As we age, cells accumulate oxidative stress and changes in iron metabolism, both of which raise the risk of ferroptosis. This process may contribute to tissue degeneration, particularly in the brain, liver and kidneys. Elevated iron stores in older adults are associated with worse outcomes in several diseases and ferroptosis may help explain why.
Furthermore, it is tightly linked with mitochondrial dysfunction, glutathione depletion and the weakening of antioxidant systems, all hallmarks of biological aging.
Protecting against ferroptosis
There are several ways the body naturally resists ferroptosis:
- Antioxidant defenses: especially glutathione and enzymes like GPX4;
- Iron regulation: proteins like ferritin and transferrin help limit free iron availability;
- Nutritional support: nutrients such as selenium, vitamin E and polyphenols may protect against lipid peroxidation.
Supporting these systems through diet, stress reduction and metabolic health may reduce ferroptotic damage as we age.
Ferroptosis is a highly specific and oxidative form of cell death that lies at the intersection of iron metabolism and antioxidant defense. Its role in neurodegeneration, cancer and aging makes it an important topic in longevity science. By learning how to detect and influence ferroptosis, we open doors to new therapies that protect healthy cells or target harmful ones, guiding us toward more precise and adaptive approaches to aging and chronic disease.
