By Benjamin V. Treadwell, Ph.D.
Where did I put the car keys? Why did I come into the kitchen? Memory impairment is something we all encounter, to various degrees, as we age. So, what’s happening to us? Let’s take a closer look at some of the scientific knowledge about the aging brain and memory, including encouraging information from recent research. Animal studies indicate the potential for protecting specific areas of the brain involved in memory, and its processing, from age-associated functional decline.
Memory Formation Where and How
The hippocampus (particularly the CA1 region) is currently one of the most studied areas of the brain, thanks to earlier work showing its importance in memory formation, learning and thought. Additionally, the hippocampus reveals pathology in neurodegenerative conditions like Alzheimer’s. Recent work has also connected changes in biochemical pathways within the hippocampus to age-associated memory disorders.
How memory is actually formed still remains somewhat of a mystery. However, recent work has associated the process with changes in the flow of electrical charges, or ions (Na, K, Mg, Ca), across the nerve membrane. Exactly how a thought process or input from our environment produces this movement is not yet fully understood. But the more intense or impressive the thought or observation, the more sustained the electrical charge.
This phenomenon, known as “Long-term Potentiation” (LTP), depends on “synaptic plasticity,” a term describing a synthetic process that occurs at nerve endings (synapses) in response to nerve stimulation. It causes the nerve cell to make more neurotransmitters, and their cognate receptors, producing a robust chemo-electrical effect to propagate an electrical charge through the neuron.
The next time you see, hear, feel or think something similar, the response is much faster. The neurons involved in the initial experience are now primed (lots of stored neurotransmitters and their receptors on the neurons’ pre- and post-synaptic membranes). These neurons remain primed for a long period of time, hence “Long-term Potentiation,” which is considered the foundation for memory.
Imbalanced Ion Transport
What happens to this process as we age? Recent work implicates the dysregulation of an ion, calcium, as one of the causes for memory impairment.
The neuron activates two mechanisms to move calcium ions during memory formation: the N-Methyl-D-Asparate Receptors (NMDAR) and the L-type calcium channels. In young animals, there is a balance of these receptors for maximum function as memory-forming machines.
As we age, however, NMDAR levels decrease with a relative increase in the L-type calcium channels. This change in the ratio of the two calcium ion transporting mechanisms seems to correlate to memory impairment. The probable cause for the age-associated decline in NMDAR appears to be related to loss of a key cellular antioxidant.
Antioxidant to the Rescue
A recent report describes an experiment to determine the effects of glutathione (GSH), an antioxidant produced by the body, on levels of NMDAR in aged mice. The investigators suspected this antioxidant is an important piece of the age-associated memory impairment puzzle, as low levels of GSH and NMDAR are found in older animals and seem to correspond to memory decline.
The mice ate either a control diet or a diet supplemented with the glutathione precursor, N-acetylcysteine (NAC) for 21 days. The research team analyzed brain tissue from the mice from the specific area of the hippocampus involved in memory and cognition, the CA1 region mentioned earlier. They measured for L-type and NMDAR-type elicited neuronal activation, necessary for LTP.
As anticipated, the tissue from the mice on the unsupplemented diet showed an imbalance of NMDAR (lower) and L-type channels (higher) with impaired LTP, compared to younger adult animals. On the other hand, results for the aged mice on the NAC diet showed elevated levels of glutathione, along with a substantial increase in the NMDAR levels (in balance with the L-type channels) and unimpaired LTP. In other words, very similar to younger adult animals.
What Does It All Mean?
The above experiment seems to support a positive role for the antioxidant NAC in improving the mechanisms involved in memory formation and retention. However, this was a rodent study. Additional research will be required to determine whether the results apply to our species.
That said, the mechanisms for memory formation in mouse and man are similar and glutathione levels also appear to decrease as humans age. In other words, the memory-protective possibilities for supplementing with NAC (or perhaps another glutathione-boosting nutrient like alpha lipoic acid) seem encouraging.
Dr. Treadwell answers your questions.
question: Is it a good idea to take both Juvenon and Youthful Energy? Or should you take one or the other? — W
answer: Levels of alpha lipoic acid (ALA) and acetyl-L-carnitine (ALCAR), the primary natural substances in Juvenon (along with biotin), may decline with age. This nutrient combination, as demonstrated in animal and human studies, helps to support/stimulate cellular health and mitochondrial function for maximum energy production.
Youthful Energy enhances the Juvenon formula with nine co-nutrients to promote a healthy weight and overall health, as well as cellular health, with longer sustainability. Anecdotal evidence indicates the combined oral doses of the two supplements are well tolerated and produce a significant boost in energy. However, it’s always a good idea to consult with your own health professional about your individual needs.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor.
Two groups of investigators in Canada, from the University of British Columbia, Vancouver and the University of Victoria, recently published the results of their study on the age-associated decline in memory in the journal PLoS ONE. The article, “Glutathione Restores the Mechanism of Synaptic Plasticity in Aged Mice to That of the Adult,” details the team’s research and conclusions on the connection between maintaining memory and a healthy redox balance in brain cells.
Previous research associated a reduced redox potential (a more oxidized cellular environment) with aging and demonstrated a correlation, in the hippocampus (specifically the CA1 region), to a lower level of the major antioxidant, glutathione (GSH). The British Columbian investigators hypothesized not only that age-associated memory impairment is a consequence of this condition, but also that GSH is key to one of two related hippocampal mechanisms.
The two mechanisms are involved in calcium ion transport and necessary for memory and cognition, according to animal studies. One uses the N-Methyl-D-Aspartate Receptor (NMDAR), the other the L-type calcium channels. NMDAR activation seems to decrease with age, while the number of L-type calcium channels increases, negatively affecting long-term potentiation (LTP), a form of synaptic plasticity believed to represent a cellular model for memory.
To test their hypothesis, the research team designed a study with two groups of old mice. For 21 days, the experimental group ate a diet supplemented with high amounts of a precursor to glutathione, N-acetylcysteine (NAC), while the controls’ diet lacked the nutrient. As expected for the controls, biochemical analysis of the target hippocampal tissue (CA1 region) revealed a significant decrease in both GSH and the NMDAR.
By contrast, tissue from the mice on the NAC-supplemented diet showed not only an increase in GSH, but also more of the NMDAR. Further analysis showed that synaptic plasticity and LTP had returned to levels present in younger animals.The investigators concluded the evidence suggests supplementing diet with NAC may be an attractive solution for mediating age-related changes to synaptic plasticity. They extrapolated that higher levels of NAC for older subjects — mice and potentially man — could protect the brain against GSH depletion and, consequently, memory and cognition impairment.
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.