Ironing out memory loss

Neurodegeneration is often thought of as irreversible: Once neurons are damaged (or dead), one expects the decrease in function to be permanent. Granted, there is evidence that neuronal stem cells persist in adult brains, raising the possibility that functional could be reversed as the brain regenerates — but as the rate of damage accumulates with aging, such replenishment will inevitably fall behind. Hence, we tend to think of declining mental function as a one-way trip.

Recent findings, however, suggest that functional losses in the brain can indeed be reversed. The work of Bruce Ames and co-workers, for example, has demonstrated that potent anti-oxidants can return youthful plasticity to aging brains, at least in rats. (Bruce has a favorite joke about these results that I’ve quoted before and will quote again: He told his son, “We’ve come up with a way to turn old rats into young rats!” His son replied, “Let me know when you’re able to turn old people into young rats.”)

Further evidence of the reversibility of mental aging in the Rodentia comes from this recent paper by Martins de Lima et al.. The authors demonstrate that iron chelators can restore mental capacity in aged rats. (Iron is known to accumulate in the aging brain, and is thought to generate cytotoxic compounds termed reactive oxygen species or ROS.)

Reversion of age-related recognition memory impairment by iron chelation in rats

It is now generally accepted that iron accumulates in the brain during the ageing process. Increasing evidence demonstrate that iron accumulation in selective regions of the brain may generate free radicals, thereby possessing implications for the etiology of neurodegenerative disorders. In a previous study we have reported that aged rats present recognition memory deficits. The aim of the present study was to evaluate the effect of desferoxamine (DFO), an iron chelator agent, on age-induced memory impairment. Aged Wistar rats received intraperitoneal injections of saline or DFO (300 mg/kg) for 2 weeks. The animals were submitted to a novel object recognition task 24 h after the last injection. DFO-treated rats showed normal recognition memory while the saline group showed long-term recognition memory deficits. The results show that DFO is able to reverse age-induced recognition memory deficits. We also demonstrated that DFO reduced the oxidative damage to proteins in cortex and hippocampus. Thus, the present findings provide the first evidence that iron chelators might prevent age-related memory dysfunction.

According to the results of this study, functional loss in the brain is not (entirely) a simple steady state balance between accelerating cell morbidity and diminishing regenerative capacity. Instead, it appears that accumulated iron is be causing ongoing damage (perhaps via ROS, perhaps by some mechanism) and that this damage is not irreversible per se: As soon as the iron is removed, the brain begins to regain its youthful capabilities.

The implications for human neurological aging are tremendous: While not everyone develops a specific age-related neurodegenerative disease such as Alzheimer’s or Parkinson’s, most people suffer from a slow decrease in mental sharpness as we age. If the results in this paper hold true for primates (that is, if iron is a cause of broad-spectrum functional loss in normal human aging), and assuming that compounds like desferoxamine don’t have awful side effects (the obvious one being anemia), then iron chelation therapy (perhaps along with the elimination of other toxic metals) could become an important part of the anti-aging pharmacopoiea.