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Two Things A Lifetime Of Research On Aging And The Brain Said We Should Do Now

24/9/2020

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Dr Mattson's two findings on how to live longer better

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Photo by Aleksandar Popovski on Unsplash
After a lifetime studying the how aging and the brain interact, Dr Mark P Mattson recently retired from the National Institute on Aging. Dr Mattson is a renown expert in understanding neurobiological responses to physical exercise and dietary restriction and their relationship to ageing and age-related disease.

His two seminal findings can help us all live longer better.

As we age, our brain inevitably loses its edge. But there is detailed research which shows two specific ways in which we can slow the rate of brain aging. Both are freely available and require no subscriptions, payment plans, nor coaches. 
We're all aware of the strong positive associations between such problems as obesity, high cholesterol, and insulin resistance and the risk of major age-related diseases including diabetes, cardiovascular and cerebrovascular diseases, and many types of cancer. These problems also accelerate the aging of our brain.

It's known how some of those problems affect the brain, and for others the causative connection, if any, is not clear. However, it turns out that healthy lifestyle changes which reduce obesity, high cholesterol and insulin resistance also benefit our brain health.
​

In other words, as the scientists might put it - lifestyle interventions which improve metabolic status may counteract brain aging. The qualification "may" is a little cautious - there is a multitude of reasons to believe that just two changes WILL make quite an improvement.

The case for intervention - proven

On average, the cognitive performance of individuals who have metabolic syndrome is poorer than their age-matched healthy counterparts. Brain imaging studies have documented reduced grey matter volumes and white matter health in multiple brain regions, and reduced functional connectivity between brain regions in obese individuals, particularly those with abdominal obesity and insulin resistance.

Also, body mass index is inversely associated with glucose utilisation in the prefrontal cortex, a brain region that plays critical roles in executive function, attention, memory, and insight.

For example, when rats are fed a diet high in saturated fats and sugar, they perform worse on a place recognition task and exhibit elevated oxidative stress and inflammation in their hippocampus.

It has also been found that the ability of neurons to respond adaptively to acute metabolic and chronic stress is degraded when there is excess sugar in the blood. Excess blood sugar compromises the neurons' ability to respond to stress with Brain-derived neurotrophic factor (BDNF). This is important because BDNF promotes the survival of nerve cells (neurons) by playing a role in their growth and healthy functioning. A lack of it compromises healthy functioning.

Thus, both correlational data from human studies (and many controlled trials in animals) demonstrates that a chronic positive energy balance e.g. too many "calories in", adversely affects brain structure and function.

What do we need to do?

There are two interventions which have risen to the top over the last 20 years of research, as summarised in a 2018 report by Dr Mattson.

His conclusion, after a lifetime of study? 

- Exercise and diet are critical determinants of healthy aging.

On exercise, Dr Mattson honed in on aerobic exercise; for diet, he unequivocally nominated intermittent fasting (time-restricted eating) as the optimal eating pattern for brain health.

He also confirmed, that "attenuation of age-related muscle loss may be a converging mechanism for exercise-induced extension of healthspan". In other words, we need to take action to retain our muscle mass.

This is exciting - there is optimism among scientists that prescriptions for healthy brain aging are within our grasp - today, right now. This is supported by the emerging understanding of the mechanisms by which energy restriction and exercise enhance neuroplasticity and resistance of the brain to stress and aging. 

Recent findings suggest that feeding and exercise regimens that result in intermittent metabolic switching from liver-derived glucose to fat-derived ketones facilitate brain neuroplasticity and resilience (Mattson et al., 2018).

The brain-enhancing power of time-restricted eating

For animals, there is a raft of scientific literature which shows that, compared to animals fed ad libitum, those fed intermittently (alternate day fasting or daily time-restricted feeding) exhibit improvements in many health indicators. These improved indicators are associated with the animals extended lifespan, and with diminished metabolic markers of aging (here; here; here).

Animal experiments with time-restricted eating have also demonstrated improved cognitive and motor performance, and less brain cell dysfunction (here; here; here). This is the outcome of enhanced neuroplasticity, also known as neural plasticity, or brain plasticity.
​
Plasticity is the ability of neural networks in our brain to change through growth and reorganisation. Examples of neuroplasticity include circuit and network changes that result from learning a new ability, environmental influences, practice, and psychological stress.


What science calls for are strategies for enhancing our brain health by application of daily and weekly patterns of meal consumption and exercise that result in intermittent metabolic switching. 
​

What does this mean for us?

"Intermittent fasting", "time-restricted eating", these have become faddish enough to turn us off. I must admit, it leaves me a bit cold. When we pigeon-hole something as a fad, we don't see it as a lifestyle change, and we tend to see it as a short-term fix. A fix for which we often have unrealistic expectations, as for a water-diet, for example.

But just as for exercise, we can ease into time-restricted eating slowly. For example, at the moment I run fasted twice a week, and as we are now in Spring (Down Under in Australia), I will shortly start running every morning fasted.

It started for me because I'm very focused on warming up before running, for about 10 minutes. I did not want to get up even earlier and eat, then wait, then warm-up and then run. That would have meant getting up nearly an hour earlier every morning. So I just drink a couple of glasses of water and head out to warm-up.

I also mostly don't eat after 8 pm, and I try to fast 24 hours twice monthly. 

It is building those kinds of ideas into your life which will ensure that time-restricted eating becomes a way of life, not a short-term "fix". The goal behind what you are doing is to get the body to learn to easily switch between burning fat and burning carbs - so-called metabolic switching.

Accumulating data suggest that regular intermittent metabolic switching can counteract all of the hallmarks of aging (Mattson, 2015b).

Luckily, time-restricted eating has become a topic-du-jour, and there is a myriad of trustworthy sites with useful advice on how to get going:
  • Minifasting - how skipping occasional meals may boost health
  • Intermittent fasting for beginners: should you skip breakfast ...
  • Intermittent fasting: Surprising update - Harvard Health Blog

The point about it is this - by starting out and building some of these principles into your eating habits, you are more likely to retain your brain health and cognitive abilities for longer.

Here's the main point: you're not doing this to lose weight. You well may lose weight, and that's a nice by-product. You are doing this to stay conscious of your world and those around you for longer.

Regular exercise enhances brain health and cognitive fitness

Complementing the brain benefits of time-restricted eating, Dr Mattson identified exercise as the other most critical factor in improving our brain health. The two are linked, as exercise can be used to stimulate metabolic switching. For example, running fasted will prompt the metabolism to burn a higher percentage of fat than is running after a high-carb meal.

Regular aerobic exercise (which is necessary for the survival of many animals) has been shown, conclusively, to improve the metabolic health of our brain. It also reduces anxiety and improves cognition in laboratory animals and human subjects (here; here; here).

That is in part because exercise causes the release of beneficial hormones, improves blood flow through the brain and helps sweep up the metabolic and cellular waste which would otherwise accumulate.

Perhaps not so well known is that aerobic exercise also results in increased antioxidant defenses which not only helps our brain but our entire skeletal, muscular system. Aerobic exercise stimulates cellular adaptations that translate into functional improvements which protect against muscle-loss (sarcopenia) as we age.

In a nutshell, aerobic exercise not only delivers us better brain health but better overall muscular health.

What does this mean for us?

Here are some tips for getting started from WebMD. And if you are already exercising regularly, keep in up, and seek to balance your aerobic and strength training. The latter is necessary to maintain your skeletal muscle as you age.

Any physical activity that gets you off the couch and moving can help improve your mood. Here are suggestions from the Mayo Clinic for getting started with unstructured exercise.

Physical activity and exercise are not the same things, but both are beneficial to your health. Physical activity is any activity that works your muscles and requires energy and can include work or household or leisure activities e.g. gardening, washing your car, or walking around the block.

Start with physical activity, if you’re inactive, and build up gradually to light exercise. For example, start walking, even 10 or 15 minutes a day, and over time build up the intensity to brisk walking.

The mental health benefits of exercise and physical activity only last if you stick with it over the long term — another good reason to focus on finding activities you enjoy.

​The key is to commit to some moderate physical activity or exercise on most days.

Get started, today

Fasting and vigorous exercise are different types of challenges for our body and brain. Yet emerging findings are revealing that they each elicit similar adaptive cellular responses that can enhance neuroplasticity and stress resistance.

The fantastic news about these findings is that you can start today - go for a brisk walk, or a longer walk, or a run. Resist eating after 8 pm, and plan to skip lunch one day this week. Make sure that you have a good breakfast and drink plenty of water.

​Find a pattern which works for your lifestyle.


Good luck.
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    Since I was diagnosed at 50 with Type 2 diabetes I've been learning how to do bone-building fitness training which lowers my age. You can too. It's your choice. Walter


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