When aging begins and the path of loss and decline

If we’re saying that the vast majority, if not everything about how our brain is going to work, is set up during the development of the brain, then when does development end and function begin? We talk about homeostasis during adult life and aging, with the implication that these are segregated, but it may not be that linear nor categorical. With everything that we do as humans in our relationship with the world, we categorise things and we create definitions.

We are extremely comfortable in referring to the great apes with whom we shared our last common ancestor several million years ago. I’m fairly certain that the gorilla doesn’t call itself a gorilla. That’s what we decided to call it. Categories and definitions of the world are not intrinsic to the world. They are human-imposed definitions and categories based on some sort of intrinsic set of information that we decide to put together and how we see the world and how we see ourselves. It’s a lot easier to deal with things when they are in categories. It turns out that sometimes sticking too much to categories makes it difficult to address reality. So, we have to decide on a time point where we say, well, development has ended. Generally speaking, we would say that this is the point at which the experience of the outside world begins to shape the way the brain works and then the connectivity between those circuits and networks.

On the other hand, if the vulnerabilities that we will experience as older people in chronological time, when we are 55, 60, 70 years old, are somehow a function of how our brain develops and what happened during our younger lives, then it’s very difficult to pinpoint a time when aging begins. Perhaps a more useful way of thinking about those things is not to categorise them as three or four separate phases of our lives and therefore as the lives of our brains, but rather as a sort of continuum in which there is a tense equilibrium between the tendency to maintain things as they are, to the extent possible, and the tendency to those things because they’re used things in this case. The molecules inside the cells of our brains, the networks that these cells make, degrade because of usage, meaning renewal is still the name of the game. As long as that decline is manageable and compensated by whatever mechanisms of renewal exist in the brain, we call that homeostatic adult life. Where decline and loss overtake the rate of maintenance, we might call that aging.

It might therefore be a lot more useful to suggest that, as the equilibrium shifts between making things, keeping things and losing things, the degree to which you are aging also changes. So, in that paradigm, you’re always aging because, of course, time is always passing. There’s no question that a four-year old is older than a three-year old, but we refer to the brain aging process as the time in which the balance between maintenance and renewal on the one hand and the decline, so the loss of material, on the other hand, shifts towards the loss. This would vary from person to person, from brain to brain, even from era to era, because if, nutritionally, or because of doing sports, we keep the renewal phase longer, then we would age later. In other words, one person’s brain may actually begin to age, in the sense that I’ve just defined, in one person at 43 years old and in another at, say, 52.

I think it’s very important that we begin to understand the intrinsic properties that the development of the brain endows it with, to understand exactly for every individual where their aging might begin and where we might refer to as the zone of aging in the average of the population. At present, we tend to talk about all of these things from a very anthropomorphic perspective and talk about the aging of the human brain, the development of the human brain and so on. The truth is that the human brain, about which we have the least knowledge, is in many, many ways – at least in detailed, mechanistic, molecular and experimental terms – the one we can’t do too many experiments with.

In fact, most of what we say about the human brain, including all those things that I’ve come to describe, actually comes from research done on the brains of other animals, and those animals include species that have brains that resemble ours insofar as saying, Oh, that’s the cerebellum. That’s the cortex. That’s the hippocampus (a place in the brain that regulates the formation of memories and so on). Yet, if we dissected the brain of a mouse or a rat and looked at it under a microscope, it would look nothing like our brain. Studying the brain of a fish or a bird or a fruit fly, even those tiny flies that love to fly around your bananas in the kitchen, has given us enormous amounts of information about how the brain actually develops, how it works, how memories are formed, how behaviour is driven, what aspects of behaviour are innate and what are learned and how those interact with one another, and what neurons do and so on.

Very little of this knowledge, relatively speaking, comes from studying the human brain. So, how can we be so confident, for lack of a better term, in describing the events that happen in the human brain when most of our knowledge comes from other organisms? The answer to that, including our knowledge about aging, is evolution.

When we study these other brains, we can be fairly confident that very similar rules and processes drive the formation, the homeostasis, the function and the decline of the human brain. That’s a very important interjection. If we truly want to understand what our brain is and how it works, we have to understand how the brain works in general. We can only do that by doing research on the brains of other organisms – what we would, today, call basic research. Our ability to actually understand what might be going on in the brain of a patient who comes to the hospital has become far better, not only because of medically studying what happens to patients but because scientists over decades have spent time trying to understand how the brains of other species actually develop.

What have we learned, from studying these other brains, about the process of brain aging and how it might be regulated, that we could apply to humans? We have a lot of knowledge, yet very little understanding, of the brain. It’s similar to having massive amounts of data and needing to make sense of the data to come up with a theory. How things work when it concerns aging – when it begins, what it really is and why it results in the things that it results in and why certain brains might age healthier than other brains – remains unclear, but we do know that wear and tear happens in neural activity. When the brain is active and working, it produces toxic substances that in the end compromise the health of the cells that make up the brain; that, we do know.

The networks, as a whole, begin to respond less efficiently and less frequently and are more likely to die. Therefore, the less active the cell in the brain, the more probable it will be lost and so, as you begin to accumulate damage, you begin to lose cells; but as you lose cells, you start to lose activity. Once you lose activity, you lose cells. So, you go from this virtuous circle of replenishment and homeostasis into this vicious cycle of loss and decline. Once the equilibrium shifts, where the majority of what’s going on is loss and decline, there is an acceleration, because it reinforces itself to create other good things and bad things. This is how you get a rapid decline in how the brain works.