Brain aging research: A need for balance

Lara Lewington’s new brain aging documentary explores how brain aging is predicted, measured and possibly mitigated.

Documentary maker Lara Lewington‘s latest work, Mind Over Matter is set to air on the BBC later this month. In this documentary, Lewington delves into the intricate and multifaceted subject of brain aging on a journey that took her to some of the most esteemed institutions in the US, including Stanford University, the University of California, Berkeley, and USC Leonard Davis School of Gerontology.

Lewington also spent time with cutting-edge biotech companies like BrainKey and Fauna Bio and sought the views of leading longevity figures such as Jordan Shlain and Bryan Johnson. Additionally, Lewington’s exploration included a visit to blue zone Loma Linda, where a Seventh Day Adventist community boasts life expectancies significantly exceeding the national average.

Longevity.Technology: As global lifespans continue to increase, it is imperative that our understanding of brain aging and cognitive decline keeps pace. The phenotype of normal cognitive aging is well-documented, highlighting that while certain mental capabilities are preserved into old age, others, such as processing speed, reasoning, memory and executive functions, experience noticeable declines starting from early adulthood. These changes are influenced by a complex interplay of genetics, general health and medical conditions such as atherosclerosis, along with biological processes like inflammation and neurobiological transformations. Lifestyle factors, including diet and exercise, also play a significant role.

Recent advances, particularly in genome-wide scans and brain imaging, are enhancing our ability to identify the genetic and vascular contributions to cognitive aging, and we are continuing to develop our understanding of the pathology of neurodegenerative diseases. Understanding these factors is crucial, not only for mitigating cognitive decline but also for aligning our cognitive healthspan with our increasingly lengthening lifespans. This alignment is essential to ensure that the added years of life are characterized by mental acuity and overall well-being, rather than prolonged periods of cognitive impairment, and this means Lara Lewington’s brain aging deep dive comes at a timely moment; we sat down with her to find out more about what she found out during filming.

Lewington was sparked to make Mind Over Matter while she was filming Forever Young last year and realized just how much content and information on brain aging she had acquired that deserved an audience.

Wanting go beyond the truism of “it’s good to keep active”, Lewington wanted to look into what there is in terms of mitigating brain aging, find what the state of play is in dementia research and where the real cutting edge science is going, in addition to understanding more about what we can do to mitigate our own brain aging.

“There have been lots of devices created which conceptually are still at an early stage, so rather than leap into all of that, I wanted to discuss things that were being rolled out and that are understandable,” Lewington explains.

“I went to the University of Southern California, and met the absolutely brilliant Andrei Irimia who uses computational models to understand how our brains age,” says Lewington. “In the film, he explains how the brain ages both via natural aging, the natural deterioration, versus the actual disease process of dementia, and that they are two different things.”

Lewington explains she learned that although lifestyle is very important to both types of aging, and although there are commonalities between them, one is natural and one is caused by a disease.

“We have to look at both processes differently, and that was a really interesting place to start – taking a look at what we understand so far and how collecting lots of data on healthy brains is as important as data collected from people suffering from disease. Science has a lot of data from MRI scans, but it’s been collected from people who have reason to have an MRI scan! There is a lack of clean data, and that’s a challenge.”

Lewington says that the concept of prediction was a common theme that emerged during all her discussions.

Lara Lewington (L) with Matthew Walker PhD, Professor of Neuroscience and Psychology at the University of California, Berkeley, and Founder and Director of the Center for Human Sleep Science.

“All the data collected and tracking undertaken can identify the signs of things going wrong long before other symptoms rear their heads,” she explains. “Matthew Walker at Berkley told me about identifying the very, very early stages of Alzheimer’s; often the scientists would see signs of sleep changing, and those sleep changes are associated with the disease and borne out by deterioration further down the line. If you look, you can spot these early markers, as you can with brain scans, and see if the brain isn’t aging in the way that it should be. Similar to shrinkage in certain areas of the brain – these can be very early markers, and we know with Alzheimer’s, as we do with a lot of other medical conditions, early treatment is pivotal.”

Early diagnosis can help in developing interventions, says Lewington, and once targets are understood better, drugs can be developed better, leading, hopefully, to Alzheimer’s treatments with fewer side effects.

Lewington also visited Fauna Bio who are looking at what can be learned from hibernation in animals and what happens to the tau protein in their brains. “It’s fascinating what Fauna are doing, and it’s a good way of expressing to people how drugs get developed through AI and data – plus squirrels make for great TV!”

The next stop in Lewington’s journey was Stanford, where she met Leanne Williams, the scientist who made the discovery that you can see some forms of depression on the brain.

Lara Lewington (L) with Leanne Williams PhD, Professor of Psychiatry and Behavioral Science, Stanford Medicine.

“Leanne had all of this incredible data in a fantastic data display, and it was very interesting to learn that untreated depression can be a trigger for dementia,” says Lewington. “Being able to quantify it and actually see it, is massively beneficial for people who have depression, especially once it’s been treated.”

As well as appreciating just how complicated the brain is, Lewington says something that really stuck with her was the need for balance in the brain’s function.

“Leanne had various scores in six different categories, but it’s not about high or low scores, it’s about the balance of all of them. The miracle of the brain is that it ever functions properly, because there’s just so much that can go wrong! This really stuck with me, the idea that there is so much imbalance possible. When you look at the mental health crisis and consider the workings of the brain, it makes you really understand this need for balance.”

During her research for the documentary, Lewington says she came to appreciate how many people have a huge fear of dementia and this raises the question of early testing, and looking for those early markers.

“Something that arose from my conversation with Jordan Shlain [CEO, Private Medical] is the need for awareness of what early diagnoses can mean for patients,” explains Lewington. “It’s all very well understanding our risk and detecting the early signs of something, if we are able to treat it early when it’s practical and sensible – maybe we will make more discoveries down the line where it will be apparent if early markers will become something symptomatic that warrants intervention.”

Lewington says she has tried to present a realistic view of what is happening and that there is some comfort in that in that realism.

“People would be scared to death if suddenly we said everything was going to be transformed tomorrow – incremental change is the only possible way to go in terms of infrastructure and for the way that individuals feel.”

And while there is no danger of a sea change in healthspan infrastructure, Lewington says people should be made aware of the changes that they can make themselves.

“I have talked to these amazing leading scientists, and they all come back to lifestyle – changing your lifestyle can make a real difference now,” she explains. “If you could get the effects of exercise through a pill it would be hailed as a miracle, but most people still aren’t doing enough – and it’s not like the benefits of exercise are unknown. Every scientist, no matter how cutting edge whatever they’re discovering is, they always bring up lifestyle – sleeping enough, eating correctly, getting enough exercise.”

Lewington says she came away from the filming convinced that compressing morbidity is the way to go.

“We don’t want to be spending decades suffering from chronic disease, and that is the goal of most sensible people working in this space. We need to avoid some of these diseases of aging that happen later in life as a result of extended life expectancy – heart disease, type 2 diabetes, cancer – but it’s not just disease, it’s frailty. Trying to live too long with frailty is not a good situation.”

One way to help achieve this compression of morbidity is through early diagnosis.

“Spotting the early signs is important and wearables can help with that,” says Lewington, adding that she thinks we are heading to a place where data and AI is going to be better at helping us assess our risk.

“Testing people early, so early interventions are possible, is key to longevity,” she says. “Technology, data and AI, and what we’re starting to be able to do with it, are propelling us to a time of greater understanding which will foster earlier, more effective treatment. Or perhaps even therapies that can delay neurodegenerative diseases, pushing back dementia to beyond our lifespan.”

Mind Over Matter goes out on 29th and 30th June on BBC News and 30th June on BBC One.

Lara Lewington will be hosting a Fireside Chat on AI drug discovery with Alex Zhavoronkov at next week’s Founders Longevity Forum. Register your interest to discover how AI is accelerating drug discovery, commercialization and licensing models HERE.

Photographs courtesy of Lara Lewington. Main image shows Lara Lewington with a 3D printed model of her brain given to her by University of Southern California.