When Friends Turn into Foes

In 2060, the total population in the US over 70 years of age is projected to be more than double. Research on aging may be crucial in order to improve the quality of life of millions of people in the future, and develop a sustainable healthcare system for an increasingly older population.

A new study tackles the question: why aging healthy brains are subjected to function decline, and neurons don't perform as well as they used to.

With age, brain activity declines, no matter how healthy you are, how good is your diet, how much exercise you do, or how much social interaction you get. We become more forgetful, distracted, and performance in general is not as in our early 30s. Memory is affected at older ages, not necessarily linked to the onset of Alzheimer’s disease or dementia. Coordination, as well as our metabolism, are additional body functions affected at older ages. The reason? Your neurons don’t work as they used to. This is due to a decrease in the number of connections, called synapses, established between neurons.

But why does brain function decline with age, no matter of your overall health?

Synapses develop during the first stages of life. Once a person’s brain reaches maturity – around 25 years of age – their synapses are supposed to stabilize. In normal aging, neurons are not lost, but their synapses, which are eliminated, compromising several brain functions. But if one is free of neurodegenerative diseases, such as Alzheimer’s, or never suffered injuries, like a stroke, why are our neurons losing those synapses and performing worse?

In recent years, it has been found that the way neurons form, develop and maintain synapses is not solely up to them, but aided by other cells called glia. Glial cells in the brain have been studied in relation to their protective and supportive roles in the nervous system.

In addition, many studies have now shown that astrocytes, a specific type of glial cells, have also active roles in the formation and development of synapses, in both health and disease. Astrocytes produce and send proteins to the neurons to aid synaptic function. In other words, neurons need astrocytes to learn how to communicate to each other.

The new study from January (Boisvert et al., 2018) looked into the different genes that were activated in astrocytes at younger and older ages, looking for variations. They found that astrocytes change with age, and therefore they are involved in the synaptic decay in healthy older brains. According to the study, this is how astrocytes contribute to our brains getting older:

Astrocytes promote elimination of synapses at older ages: Astrocytes in aging brains increase activation of certain genes that at early stages in life eliminate synapses that would not be needed. The re-activation of these genes in healthy older brains promotes the elimination of synapses, driving some of the age-related brain function decline. Interestingly, these genes are also active in some neurological disorders such as schizophrenia, or Alzheimer’s disease.
The brain regions especially affected by age show also major changes in astrocyte genes in the older brain: The changes in astrocytes genes are especially prominent in brain regions that are more affected by age, the cerebellum and the hypothalamus. These brain regions are involved in coordination and metabolism, functions largely affected by normal aging.
Astrocytes produce less cholesterol: They found that astrocytes decrease the genes associated to cholesterol production, which is absolutely necessary in the brain. All cells, including neurons, need cholesterol to build their structures and carry out their function. However, the cholesterol available in the rest of the body cannot go through the blood-brain barrier to reach the neurons. Therefore, astrocytes are in charge of the “local” production of cholesterol. At older ages, the restriction in cholesterol production by astrocytes deprives the brain from its source, compromising healthy neuronal function.

Why do astrocytes, after supporting neurons throughout life, seem to turn against them at older ages? Why do astrocytes seem to prepare the older brain to suffer from neurodegenerative diseases? What makes them turn from friends to foes?

Unraveling the molecular mechanisms responsible for normal aging in the brain may shed light on why some people are predisposed to diseases that affect older populations, such as Alzheimer’s or Parkinson’s disease, and reveal new targets – like astrocytes and their molecular pathways – for potential treatments, or intervention before the onset of age-related diseases.

After all, we are not getting any younger.