Why Does The Brain Age? The Answer Lies In The Genes

The brain ages in the same way that all the structures and systems of our body do. However, there are people who seem to be affected by the passage of time more than others; not only in his physique, but also in his abilities. Why is this happening? What’s more, what can we do about it? Are some people more prone to aging or do we have tools to delay the effects of the passage of years?

Apparently, the answers to unraveling the mystery of brain aging lie in certain genes. A group of researchers at the Babraham Institute in Cambridge (UK) and the Sapienza University in Rome (Italy) have found the answers by delving into the genetic gears that influence the complex mechanism of age-related cognitive decline.

The truth is that we already know a good part of what happens when the brain ages. For example, neurons are known to deteriorate and die, only to be replaced by new ones. This process is facilitated by one type of stem cell, neural stem cells (NSC). These are cells of the nervous system that can regenerate themselves and give rise to progenitor cells.

However, with the passage of time, these cells become less functional, which makes our brain too.  But what causes the aging of these cells? What exactly are the molecular changes that are responsible for its deterioration? These are the questions that researchers have found answers to.

What happens when the brain ages?

Before seeing why the brain ages, let’s see what brain aging consists of.  Brain aging is inevitable to some extent, although not uniform. In fact, it affects all brains, but differently. Slowing the aging of the brain or stopping it completely would be the best elixir to achieve eternal youth.

The human brain contains about 100 billion neurons interconnected through trillions of synapses. Throughout our lives, our brain changes more than any other part of our body. From the time the brain begins to develop in the third week of gestation until old age, its complex structures and functions are changing.

During the first few years of life, a child’s brain forms more than a million new neural connections per second. Brain size increases fourfold in the preschool period and by age 6 it reaches about 90 percent of adult volume.

The frontal lobes, which are the areas of the brain responsible for executive functions (such as planning, working memory, and impulse control), are among the last areas of the brain to mature. In fact, they may not be fully developed until 35 years of age.

But at a point, we start to get old. As we age, all of our body systems gradually decrease their ability to perform, including the brain. Thus, certain changes in memory are associated with normal aging.

Common memory changes that are associated with normal aging include:

• Difficulty learning something new : memorizing new information can take longer.
• Difficulty multitasking: Slow processing can make it difficult to process and schedule parallel tasks.

• Difficulty remembering names and numbers : The strategic memory that helps to memorize names and numbers begins to diminish at age 20.
• Difficulty remembering appointments.

While some studies show that a third of older people have difficulties with declarative memory (memories of events or events that have been stored and can be retrieved), other studies indicate that a fifth of people in their 70s perform cognitive tests as well as those in 20 years.

The general changes identified during brain aging would include:

• Brain mass. Contraction in the frontal lobe and hippocampus (areas involved in higher cognitive function and the encoding of new memories). The changes start around age 60 or 70.

• Cortical density. Thinning of the outer surface of the sulcus due to decreased synaptic connections. Fewer connections can contribute to slower cognitive processing.
• White matter. White matter consists of myelinated nerve fibers that are grouped into tracts and transmit nerve signals between brain cells. Myelin is thought to shrink with age, slowing processing and reducing cognitive function as a result.
• Neurotransmitter systems. Researchers suggest that the brain generates fewer chemical messengers with aging, and it is this decrease in the activity of dopamine, acetylcholine, serotonin, and norepinephrine that may play a role in memory and cognition decline and a increased depression.

The role of genes as the brain ages

Now that we know what happens when the brain ages, let’s go back to the study we mentioned at the beginning to see the role of genes in this process. Apparently, according to the researchers, the Dbx2 gene may explain brain aging. 

The researchers compared genetic changes in neural stem / progenitor cells (NSPCs) from old (18-month-old) and young (3-month-old) mice. In doing so, they identified more than 250 genes that changed their behavior over time, meaning that these genes are likely to cause the target cells to malfunction.

Once they narrowed their search to 250 genes, the scientists noticed that increasing the activity of the gene called Dbx2 seemed to change aging NSPCs. They conducted in vivo and in vitro tests that revealed that increased activity in this gene in young NSPCs causes them to behave more like old stem cells. Increased Dbx2 activity prevented NSPCs from growing or proliferating as young cells do.

Additionally, in older NSPCs, the researchers identified changes in epigenetic markings that may explain why stem cells can deteriorate over time. If we think of our DNA as an alphabet, epigenetic marks are like accents and punctuation marks, telling our cells whether and how to read genes. In this research, the scientists discovered how these marks are placed differently on the genome, “telling” the NSPCs that they should grow more slowly.

With this study, researchers have shown that these changes can contribute to brain aging by slowing down the brain renewal process. Researchers are hopeful that these findings will one day lead to the reversal of the aging process. By understanding how aging affects the brain, at least in mice, the researchers hope to identify ways to detect neural stem cell decline.