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Neurobiology And Aging

In order to understand how the "slings and arrows" of aging can affect the brain, some basics of neurobiology must be appreciated.

Neurons lack the capacity to regenerate. With a few exceptions, new neurons are not produced once the maximum number is established early in life, and the ability of CNS neurons to be repaired when damaged is quite limited. We can lose neurons as we age, but we cannot grow new ones. The exact number of neurons lost by the human brain during aging has been elusive, plagued by methodological issues that include technical difficulty in counting neurons, post-mortem changes that can occur in human brains from autopsy, differences in the pre-mortem condition of young and old people who are autopsied (for example, older people are more likely to have died from chronic illnesses that could have resulted in brain pathology), and the unwitting inclusion of patients with undetected dementia. Even when nonhuman animals are studied, inconsistencies arise, stemming from species differences, variability among genetic strains within the same species, and the fact that different parts of the brain often show different age changes. All of this suggests that no general pattern of neuron loss occurs in aging nervous systems. However, there is a growing consensus that some older studies probably overestimated the degree to which neurons die as people age. The current view is more optimistic: at least in the neocortex, many (perhaps most) healthy older people exhibit a minimal loss of neurons, although other brain regions may be more vulnerable.

Neurons require a disproportionate share of the blood supply. Neurons have a ravenous appetite for the blood's precious cargo of glucose and oxygen, and the percentage of the body's blood and oxygen consumption in the brain at any time is far out of proportion with the rest of the body. It has to be this way because reducing the supply of blood/oxygen to neurons results in impairment, damage, or destruction depending on the severity and duration. Thus, conditions that reduce the brain's blood supply, such as atherosclerosis, diabetes, and, of course, stroke are cause for concern. Each of these conditions becomes more prevalent with age, as do other changes in the vascular system serving the brain, even in the absence of diseases.

Neurons are at risk from various toxins. Over a lifetime, neurons, like other cells, are exposed to toxins. These can be environmental or endogenous—produced by the brain itself. For example, glutamate is the major neurotransmitter used by neurons to synaptically activate (excite) other neurons. Under certain conditions, such as hypoxia or tissue damage, the effects of glutamate can become exaggerated, resulting in excessive entry of calcium into the neurons, and such excitotoxic events prove to be damaging to neurons. If aging were associated with weakening of the defenses against excitotoxicity, negative age effects could accrue. Indeed, this process appears to be involved in certain types of dementia and neurodegenerative conditions that can accompany aging.

The neuron's nucleus regulates many functions. The synthesis of proteins is coded by DNA, the genetic material found in the nucleus of neurons and other cells. Many varieties of protein are produced for use as structural components of neurons (e.g., the microtubules and microfilaments in axons that transport molecules used for neurotransmitters and provide structural support), enzymes that control the numerous biochemical reactions necessary for cellular activities, synaptic receptors, and many other uses. Damage to DNA that can accrue in cells with age has the potential to alter many facets of neuronal physiology.

Dendritic branches and spines are at risk with aging. The size, shape, orientation, and complexity of the neuron's dendritic tree have a great deal to do with the number of functioning contacts that can be made with other neurons. Dendritic spines are small extensions that provide many additional sites for synapses. One of the best documented age-related changes in neurons is a reduction in the number of dendritic branches and spines. Even if neurons do not die off, a loss of synaptic contacts is likely to reduce the information-processing capacity of neural circuits, negatively affecting brain function.

Parts of the brain are differentially vulnerable to aging. Age effects vary greatly among different components of the nervous system. Various behavioral and cognitive functions are affected to different extents, depending on how each brain region fares. For example, the hippocampus is very important for storing memories. Research has shown that portions of the hippocampus are often damaged during aging, and this may be responsible for learning and memory deficits.

The speed of information processing slows with age. Behavior and cognition tend to become slower with age. Indeed, behavioral/cognitive slowing has been proposed as a marker of aging (i.e., a measure that can differentiate chronological age from functional age). There is a good deal of research indicating a general slowing of brain processes, with cognitive slowing likely to reflect the sluggishness of smaller components (sensory, motor, and interconnected central circuits). Possible causes of slowing might include slower conduction of action potentials because of changes in the axons; slower synaptic transmission because of structural and/or chemical changes; diminished intracellular metabolism (e.g., associated with damage to energy-producing mitochondria); reduced production of neurotransmitters or other critical products; impaired gene expression (e.g., associated with DNA damage); and many other potential changes that would interfere with optimal neural performance. Changes in the peripheral sensory and motor systems (e.g., loss or thinning of axons) probably make only small contributions to slowing. More salient are the central neural circuits that intervene between stimuli and responses.

Additional topics

Medicine EncyclopediaAging Healthy - Part 1Brain - The Nervous System And Its Complexity, Organization Of Neurons Into A Nervous System And Basic Neuroanatomy