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The brain begins its decline at age 44.
Yeah! Precisely when you need it the most, the Neurons in the Brain get stressed because they are unable to get sufficient fuel for their needs.
This loss of energy (hypometabolism) affects the Neuron’s signaling capacity.
This degeneration accelerates in the 67th year. It plateaus in the 90’s.
The degeneration in the Brain is driven by Neuronal Insulin Resistance or when the brain cells stop responding to insulin. So, insulin helps move glucose from the blood into cells. The cells tap this glucose for energy. Insulin resistance sets in when cells stop responding appropriately to insulin. This means the cells can’t use the glucose for energy or store it efficiently.
But, it’s never too late!
The team behind this new study found that interventions in a ‘critical midlife window’ could help slow down the brain’s decline. In a release issued by the Stony Brook University, lead scientist Lilianne R. Mujica-Parodi explains:
“We’ve identified a critical midlife window where the brain begins to experience declining access to energy but before irreversible damage occurs, essentially the ‘bend’ before the ‘break.’
During midlife, neurons are metabolically stressed due to insufficient fuel; they’re struggling, but they’re still viable. Therefore, providing an alternative fuel during this critical window can help restore function. However, by later ages, neurons’ prolonged starvation may have triggered a cascade of other physiological effects that make intervention less effective.”
For this study published in the research journal, PNAS, the team analysed 19,300 people across four datasets to understand ‘functional communication between brain regions (brain networks)’. They used this to map the trajectory of cognitive decline.
Other key findings
- Brain networks do not decline in a linear fashion.
- Cognitive decline follows an S-shaped curve. There are clear transitions at ages 44 and 67.
- Biomarker analysis showed that metabolic changes occur first. These are followed by vascular and inflammatory changes.
- Analysis of Gene expression – the process by which genes encode proteins which dictate how the cell functions- threw up 2 proteins that were ‘implicated’ in this ageing pattern of the brain, viz.,– GLUT4 is a protein that asks cells to respond to insulin’s signal to transport glucose from the blood to the organs. It is found in the skeletal muscle, heart, adipose tissue, and brain.- And Apolipoprotein E (ApoE) is a protein that helps transport cholesterol and fats. It also helps in injury repair in the brain. FYI, ApoE is a known risk factor for Alzheimer’s.
- The gene expression analyses also identified another protein MCT2 as a ‘potential protective factor’, meaning it could protect the brain from ageing. Now, MCT2 transports ketones in brain cells. Ketones are essentially acids that the body makes when it is burning fat instead of glucose to produce energy.To test if the brain would benefit from a ketone boost when access to glucose declines, researchers gave 101 participants doses of glucose or ketones at different stages of the aging trajectory. They found that the dose of ketones “effectively stabilized deteriorating brain networks.” The effects however, differed significantly across ages:
- The ketone dose showed maximum benefits during the midlife “metabolic stress” period (40-59 years) after which brain networks begin destabilising.
- Young adults (20-39 years) showed moderate benefits.
- The dose had diminished impact in older adults (60-79 years). This was because by the 60’s, brain ageing had accelerated. Plus, the presence of other vascular issues further reduced the beneficial effect of the ketones.
The Takeaway
No, do not switch to a Keto diet or take ketogenic supplements to delay brain ageing just yet. Because this research is still new. The scientists admit as much in their paper where they say their finding could be used to direct future interventions in brain health.
What we can do instead
Work to keep our brains fit in the 40’s itself. And there are many -often fun- ways to do so, which are also backed by science. Plus, these benefit people at all ages, even those who are 50 and over.
Head here to see what a geriatrician recommends you start doing to keep your brain fit.
Speaking of keeping the brain fit, how does playing a few games on your phone to check your cognitive health sound? Cool, right? Well, it can be done. In fact, look at what Indian cognitive health start-up Ivory found when they got people to play (or take a test)…
Depression, Anxiety speeding up Cognitive Decline in Urban India
The Ivory Brain Health Primer report gives more reasons to prioritise Brain Health in the 40’s.
One in four urban, educated Indians have scored 15% lower than average on a cognitive assessment conducted by the Indian cognitive health start-up, Ivory. The common factor: they all suffered from either anxiety, depression or post traumatic stress disorder (PTSD).
“So, we asked people whether they were clinically diagnosed or had reported at any point of time any of these four conditions. If they did, we correlated those scores. So 25% of the respondents had one of these conditions and those 25% essentially scored 15% lesser on their cognitive test,” said Issac John, co-founder of Ivory.
Issac, who I met last week, was the first to point out that the assessed cohort is not a representative sample size for the Indian population. Only 102 individuals took this FDA-approved cognitive assessment on the Ivory platform. 86% were aged over 45 years and the cohort had a 3:2 working to retired ratio.
Yet, some other key findings should worry us a bit:
- 10% individuals were at high risk for future cognitive impairment.
- 71% had at least one clinical risk factor for Dementia – hypertension and diabetes being the most common.
- 40% lived alone, 50% reported low social stimulation – both key risk factors for brain health.
- Nutritional deficiency, especially for neuroprotective Omega-3 was widespread. 64% reported they didn’t consume foods with the nutrient.
- Participants scored above average on skills for memory and attention. They scored lower on skills that needed perception and reasoning.
- The good news: 88% got average or above average scores on these tests.
Ivory also administered a mini-assessment to 4711 urban Indians. 3 out of 5 individuals were over 50 and there was an even 1:1 split between working and retired people.
Here’s what they found:
- 32% had brains that were older than them by 2 years or more (a cognitive age higher than their chronological age)
- Among men, 40% had brains that were ageing faster.
Why should we care?
The tests are not a representative sample as mentioned earlier. However, the results are enough to give us reason to pause.
“As Issac puts it, “once you get to your late 30s or early 40s, we recommend that you test once every two years, just to check. One of the things is the brain is very forgiving. So, if you are at risk, it takes a long time for the condition to actually become serious. If you take early action, you are actually giving yourself the best chance to, you know, like delay or maintain good cognitive health.”
Reason enough in my books to get a cognitive assessment, along with that annual health check-up. After all, don’t we all want to get to the C-suite someday? And stay sharp enough to handle our finances or solve the daily crossword as we age?
So give your Brain the TLC (tender, loving care) it deserves!
(In case you want to get a cognitive health assessment done, head to Ivory on the web or download their app.)
Before You Go
Reason #2 your 40’s are more important than you think!
Anecdotal evidence or your own experience would tell you that most people get their first big age-related ‘health shock’ in their 40’s or 60’s. New research shows it is true.
A Stanford Medicine study had found that our bodies undergo two periods of rapid change in our lifespan, around the ages of 44 and 60. This is when many of the molecules and micro-organisms in our body dramatically rise or fall in number.
The study found that people in their 40s showed significant changes in the number of molecules related to alcohol, caffeine and lipid metabolism, cardiovascular disease, and in skin and muscle.
For those in their 60s, changes were linked to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and in skin and muscle.
What it means for us: If you are in your 40’s, now is a good time to take stock of your health (if you haven’t already). Pay attention to those test results and the doctor’s advice. Act now.
Genetics professor and the study’s senior author, Michael Snyder’s quote sums it up. He says, “I’m a big believer that we should try to adjust our lifestyles while we’re still healthy.”
Think this sounds familiar? Yes, I first reported the study in this Aug 2024 issue. But I thought it worth a throwback just to underscore the importance of the fourth decade of our lives.
Now you know why your 40th birthday is called the ‘Big 4-O’!
That should be enough food for thought (pun intended) this week.
At the risk of sounding like a broken record, do remember it’s never too late to start investing in your mental and physical health, even if you are over 45!
Want to know how you can do that and slow down Ageing? Check out Longevity Shot
In Episode 3 of the podcast from Never Too Late, Darshit Patel, chief scientific officer of Decode Age, talks about ageing, and biological age.
He also lists some steps all of us could take to get started with reversing our biological age. Spoiler: Most of them are free!
Stream it here: Substack, YouTube, Spotify if you haven’t already.
I will see you Monday.
Kavita Krishnan.
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