Default Mode Network # 3

Lay Abstract

This is what happens to our brain as we age

Yellow, Orange, Red lines show that there is no decrease in blood flow or glucose use or oxygen use from 20 to 80 years. But there is a change in how the brain metabolizes glucose (aerobic glycolysis or AG) that is the blue line. We are using glucose less toward formation of new memory and emotion at older age than when we were younger. Now take a careful look at the variation as we age, what was an asset when we were younger becomes a liability when we age. Lower the value is peaceful the mind, at rest. Alzheimer’s disease patients have higher AG values. My dream is to make a rodent model of this AG. My final posting will be how to reduce AG, clue meditation.

Chandru Jr, Biochem 71-74

Below is the details 

Let us get the facts first:

As we get older does the flow of blood to our whole brain decrease?

The answer is NO.

As we get older does our whole brain use less oxygen?

The answer is NO.

As we get older does the glucose uptake decrease in the whole brain?

The answer is NO.

In short, the total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, from 20 to 82 years of age (yellow/orange/red line in the figure).

But, look at the blue line, there is decrease in aerobic glycolysis as we age, is it good or bad? Aerobic glycolysis means emotion and memory, we needed it when we were younger but are not so important when we age. Emotional response is OK when younger, but the society expects us to react with a reasoned response when old. But, you still need aerobic glycolysis to refresh synapses, don’t stop learning. A decrease in aerobic glycolysis gives us the energy to increase the blood flow to focus on the job at hand.  may be a good thing because we are not spending all the energy in emotion and memory as we age, we must be efficient in getting the job done, namely synaptic transmission. That means you are making decisions not based on emotions but based on what is needed for me. Let me remind you also that these measurements are done at rest with eyes closed, ears plugged, there is no sensory input. This is the reaction of your brain. But, look at the figure more carefully, the variations among individuals has become greater as we age. A 70-year-old can have the same aerobic glycolysis as a 30-year-old.  That means, if a 70-year-old has the same emotional reactions as a 30-year-old person, we may call them immature, emotional and unreasonable.

I said in my previous postings that brain uses glucose metabolism for two purposes, synaptic maintenance and growth (aerobic glycolysis); synaptic transmission (oxidative metabolism). In another word, how refreshed our memory and emotion are and how fast we process the information. As we get older, we lose the power to refresh, quality vs. quantity struggle, that is why learning throughout our life is important. 

I guess your question is, what should I do to lower my “aerobic glycolysis”? Finding the balance, quality vs, quantity. That will be my last posting. Before that I should focus on the biochemistry of how the brain does this aerobic glycolysis, who are the players and how do they coordinate? Restless brain to start with. Several recent studies have revealed that high DMN cortical regions exhibit high amounts of AD pathology. Subjects with high AD pathology in these regions have significantly reduced functional correlations within the DMN. This is the main reason for me to get back to brain, a research project, to combine this aerobic glycolysis with Alzheimer’s disease to develop an animal model so treatment can be tested.  

is the PET image of what happens as you age, see the remarkable difference in the way brain uses the glucose.

Yellow color is maximal aerobic glycolysis and red is lower aerobic glycolysis.

Coming back to the subject, when we are young, you want to generate as many synaptic contacts as possible and to grow these synapses, as you get older you want to retain these synaptic connections and if possible develop new synaptic contacts. This is the struggle.

Let us get back to from the beginning, from birth.

This is the profile of brain growth from birth.

Though I want to focus in this posting on aging, I should tell you that adequate nutrition in the first 1000 days has a tremendous effect of the development of the quality and quantity of aerobic glycolysis in the developing brain and therefore gut microbes may play a significant role. These topics have greater societal importance.

There is a question if the changes in aerobic glycolysis that occur with normal aging could be influenced by how we developed the connections during the first 5 years of life. In other words what happens to your brain when we are a senior citizen could come from what happened to us when we were a child?