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Most of our information on how the brain ages is focused on deterioration in function. Even this is not simple. Two processes go on simultaneously: maturation, and the acquisition of knowledge and skills; and aging, which implies a reduced ability to learn new things, remember new items in life, together with lessened agility and an increased tendency to lose one’s balance. So while young men are usually better at sport, or learning to play computer games or new languages than older ones, it is the latter who run companies, direct armies and rule nations. Experience does much to counterbalance brain aging. But what happens in the brain?
It used to be thought that the brain lost nerve cells (neurons) during later life. Since neurons, unlike many cells in other parts of the body, can’t be replaced (though there are exceptions to this: see below), it was assumed that neuronal loss might account for age-related decline in brain function. In fact, more recent studies have shown this to be much less that was once thought. Of course, in those suffering from Alzheimer’s disease, an age-related event, there is profound loss of neurons, and the division between ‘normal’ and ‘pathological’ aging is not always clear. What does seem to happen in older humans is a loss of connectivity in the brain. For example, the density of connections (synapses) in the frontal lobes decreases with age. Why does this happen, and can it be slowed down?
A popular theory involves damage by oxidation. The body produces a highly reactive type of oxygen during metabolism. If this is not removed it can damage cells, including neurons. There are special enzymes that remove this type of oxygen, and these tend to become less efficient with increasing age. However, attempts to improve removal of reactive oxygen have not been very effective, so this theory is still questioned.
Another theory, more recent, concerns glia. These are cells in the brain that lie around neurons, and have many important functions (for example, they make myelin, the substance that wraps around nerve fibers and enables them to conduct impulses). They change with age, and this may have a knock-on effect on neurons or their connections. If this is true, then the secret of brain aging lies with the glia.
Glia are also concerned with inflammation (I wrote a recent blog about inflammation in the brain). They produce substances (including those called cytokines) that, under certain circumstances, can damage the brain. Inflammation tends to increase in older people, since their immune system becomes less effective. The connections between neurons, the synapses, are sensitive to inflammation.
Older people tend to become diabetic, and the hormones associated with the regulation of blood sugar, and sugar itself, can have deleterious actions on the brain. It is well-known that type 2 diabetes is a risk factor for later Alzheimer’s. So if there is less effective control of blood sugar, or changes in the hormones (eg insulin) that regulate how the brain uses it, this may contribute to aging of the brain. Obesity can also alter the same hormones, and has been suggested to accelerate brain aging.
Neurons themselves may show age-related alterations in function, which may reduce their ability to form new connections, or resist potentially damaging agents. Mitochondria are the energy producers of all cells, including neurons. They can change with age, and this may interfere with how the brain operates. It may also make them more susceptible to the reactive oxygen molecules mentioned above.
The hippocampus is a region of the brain particularly concerned with forming new memories. Aged animals show loss of connectivity in the hippocampus, and methods to counter this also improve their cognitive performance. The hippocampus is one of the few regions of the brain that can make new neurons during adult life. Interestingly, hormones can affect both connectivity and the formation of new neurons in the hippocampus. Estrogen has been show, in experimental animals, to increase hippocampal connectivity, which may be relevant for post-menopausal women. Cortisol, the stress hormone, decreases formation of new neurons: cortisol tends to increase with age (though this may be individually variable).
Can we do anything to reduce or delay aging of our brains? There is increasing evidence that we can. The important fact is that there are many ways that the brain can age, so there may be many possible future remedies, and these may differ between individuals. Reducing intake of saturated fats and refined sugar has been shown experimentally to slow down brain aging. Exercise is also beneficial; aged rats made to run regularly showed improved cognition compared to those leading a more sedentary life (which aged rats, like humans, tend to do). More effective ways of reducing inflammation may be helpful, acting either on inflammation itself or on the immune system. Post-menopausal hormone treatment may be effective in some women, though this remains controversial: it may be one example of the importance of personalized medicine). There are methods of antagonizing the effects of cortisol (I will return to this in a later blog). There is some evidence that certain compounds in food (curcumin is one) can delay brain aging.
Some people retain high levels of cognitive ability well into their eighties and beyond, other do not. Until we know why this is, we struggle to combat aging of the brain in an increasingly aged population.
