How Do Genetics Affect Brain Aging?

Why do some people's minds deteriorate at a young age while others' remain sharp into their 90’s? Read on for the surprising answer.

It's an undeniable fact of life: you age. And as the birthdays begin to fly by, your brain ages alongside the rest of your body. But not to worry, this process -- called brain aging -- is perfectly natural.

According to the National Institute on Aging, certain parts of the brain shrink as you age -- especially those tied to learning and other complex mental activities. But there's a catch: the changes that happen in the brain vary from individual to individual, and genetics may be the culprit.

There's a long-standing question in genetics: how much do our genes affect the way our brains age, and how much is affected by our environment?

After all, it's well-known that certain lifestyle habits -- like heavy smoking and excessive alcohol consumption -- are associated with accelerated brain aging. But what about genetics?

By learning more about the genetic factors that influence brain aging, you can explore early detection and prevention options -- especially if you're at higher risk.

Ready to dive in?

What happens to your brain as you age?

Everyone's brain is different. That includes the way the brain ages.

And various factors are tied to the normal brain aging process in older adults. For example, many of these changes are linked to your memory strength (so if you've suddenly started forgetting where you left your keys, your aging brain really could be the culprit).

Common memory changes you may notice with an aging brain include:

• Difficulty learning something new
•  Trouble multitasking
• Difficulty recalling names and numbers
• Failure to remember appointments or other important events

One reason for these changes are literal physical changes to your brain itself. Some examples of these changes include:

• Shrinkage in the frontal lobe and hippocampus -- areas of the brain crucial to cognitive function and deciphering new memories.
• Thinning in cortical density due to declining synaptic connections. Fewer of these connections may lead to slower cognitive processing (a bit like how the processor in your old laptop slows down over time).
• White matter composed of myelinated nerve fibers -- which carry nerve signals -- begins to shrink.
• Neurotransmitter systems change (the neurotransmitter system is often thought of as the chemical messenger, like a phone that texts messages to all your chemicals). 
• Chemical messengers decrease with age -- including dopamine (which influences mood), serotonin (which can affect your sleep, digestion, and more), and norepinephrine (affecting your "fight or flight" response).

What health conditions are associated with accelerated brain aging? 

First things first, everyone experiences brain aging. However, a rapidly aging brain is related to an increased risk of cognitive decline and other brain-related health conditions. These include:

• Dementia
• Alzheimer's Disease (a form of dementia)
• Cerebrovascular Disease
• Lou Gehrig's Disease
• Parkinson's Disease

Do genetics play a role in how fast your brain ages?

While your genes are not your fate, they do play a role in how quickly your brain ages.

Recently, researchers trained a special neural network (called a CNN) to predict the body's age based on a whole body MRI of about 20,000 subjects.

As a result of this test, the mean absolute error (which expresses how accurate a measurement is) between predicted "body age" and actual chronological age was just 2.5 years.

Another recent study reported that a CNN for predicting brain age based only on MRI analysis achieved a mean absolute error of 2.14 years.

Both studies reported mean absolute error of about 3.5 years between the assessment and the true chronological age of subjects. They also found an association between a specific gene location (the chromosome 17 locus) and brain aging.

In another 2021 study from USC, researchers asked whether a more accurate evaluation of brain age leads to better identification of novel genetic factors associated with brain aging.¹

To answer this question, researchers used imaging data to create statistical models for predicted brain age (or PBA). To obtain a more accurate PBA than previous research, the USC team trained a CNN model on 16,998 UK Biobank subjects.

Next, they calculated relative brain age (or RBA) -- a metric that describes a subject's predicted brain age relative to their peers'.*

Then, the USC team conducted a genome-wide association study (or GWAS) to identify single nucleotide polymorphisms (or SNPs -- changes on a gene) significantly associated with relative brain age.

Their GWAS showed that a whopping 80 SNPs from four independent loci (think of loci like a "genetic street address" telling you where something is located on a gene) show significant associations with relative brain age derived from a CNN (again, that's just a special neural network scientists use).**

This study helped identify novel associations between certain SNPs and brain aging -- a potential major breakthrough for our understanding of the aging brain.

Are you genetically predisposed to rapid brain aging?

Currently, the best way to determine your risk of rapid brain aging is with thorough analysis of your DNA.

A DNA kit is simple to use, and your DNA test result can reveal answers about how your brain ages based on your unique genetic profile.

Once you've taken an at-home DNA test, you can use your raw DNA data to further analyze your genes. If you already have your DNA test result, sign in to Genomelink's secure dashboard to find out more about your risk for rapid brain aging.

* This is based on CNN-derived predicted brain age.

** These SNPs include rs10009513 and rs12185268 in the MAPT-AS1 gene on chromosome 17. It has been reported that mutations in the MAPT gene have been associated with dementia and Parkinson’s disease.

¹ Ning K, Duffy BA, Franklin M, et al. Improving brain age estimates with deep learning leads to identification of novel genetic factors associated with brain aging. Neurobiol Aging. 2021;105:199-204. doi:10.1016/j.neurobiolaging.2021.03.014

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