Monday, March 29, 2010

Iron man is invincible but not an iron imbalanced brain: a hallmark of aging

Age is a risk factor for brain damage and neurodegeneration. Interestingly, although many living creatures experience a degree of brain decline during aging this is not as marked as the one experience by humans.
“Of the millions of animals on Earth, including the relative handful that are considered the most intelligent — including apes, whales, crows, and owls — only humans experience the severe age-related decline in mental abilities marked by Alzheimer’s disease” Harvard gazette referring to Bruce Yankner talk.
While evolution of human brain explains this fact, different factors one of which is iron accumulation, account for the development of age-related degenerative brain changes.

What’s iron?
Iron is the sixth more common element in our galaxy, the second most prevalent metal on the earth and one of the essential elements for biological functions of living organisms.
"Although total body content of iron is about 4 g in an adult male [women typically have smaller amounts than men], erythropoiesis, the most relevant iron-requiring physiological event, utilizes about 0.02 g. The amount of iron needed by an adult male can be obtained by absorbing 1-2 mg of iron. In this context, mechanisms that participate in iron conservation and recycling are essential because typical human diets contain just enough iron to replace small losses. The brain particularly needs iron for multiple physiological processes. Iron is a cofactor for [hemoglobin, myoglobin and iron-containing enzymes such as catalase, cytochromes] tyrosine hydroxylase, tryptophan hydroxylase, xanthine oxidase, and ribonucleoside reductase. [Iron] Fe also participates in myelination, mitochondrial energy generation, and DNA replication/cell cycling" (Salvador, 2010).

Iron and Cognitive decline:
“Cognitive decline is due to a slow accumulation of genetic damage in the aging brain, with Alzheimer’s showing the most severe form of this damage, called double strand breaks. Though the source of the damage is not yet clear, one culprit, may be the accumulation of metals in the brain over time, particularly iron” Harvard gazette referring to Bruce Yankner talk.
A review published in the J Neurochem von Bernhardi, Tichauer & Eugenín describe the effects of iron accumulation during aging as follows:
“Iron progressively accumulates in the brain with age, which is normally associated to changes in iron metabolism and/or homeostasis. Iron accumulation affects protein modification, misfolding and aggregation. Besides, it has an important effect on production of radical species and eventually oxidative stress. So iron accumulation becomes itself an aging promoting mechanism. The iron accumulation is quite specific and involves the accumulation of iron-containing molecules in certain cells, particularly in brain regions that are preferentially targeted by neurodegenerative diseases such as AD [Alzheimers’s disease] and PD [Parkinson’s disease]”
Iron homeostasis plays and important role on brain aging, however the molecular mechanisms involved in the deregulation of iron levels with age are not understood in detail, thus more insights on this regard warrant important discoveries and novel therapeutic approaches to combat neurogenerative diseases, which are increasing concomitantly with human life expectancy.

von Bernhardi, R., Tichauer, J. E., & Eugenín, J. (2010). Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. Journal of neurochemistry , 112 (5), 1099-1114. URL

Salvador, G. A. (2010). Iron in neuronal function and dysfunction. BioFactors (Oxford, England). URL

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