40/60 Metabolism Waves Explored

Dr Jedha, Host

Hello wonderful people and thanks for joining me today. 

When I was searching the academic databases to research another episode of the podcast, I came across a fascinating study published in August 2024. This study by Stanford researchers looked at aging in a way that hadn’t been done before. Then I also found another earlier study from the same university, published back in 2019, that built on a similar idea.

Together, these two studies paint a very different picture of aging than what most of us imagine. We tend to think of aging as a slow, steady decline. But according to these studies, our bodies don’t age in a straight line. Instead, we go through waves of change — big biological shifts that happen at predictable ages: one in the early 40s, another around 60, and possibly even another wave in our late 70s.

And here’s what makes this so fascinating: these shifts aren’t just about gray hair or wrinkles. They involve changes in the very proteins and pathways that control how we process fats, carbohydrates, and how well we handle inflammation. In other words, these biological shifts happening under the surface are directly tied to blood sugar, insulin, and the same processes that drive type 2 diabetes and prediabetes. Which is exactly why I wanted to share this research with you today, and also what it could mean for us all at these different stages. 

In the 2024 study, the researchers looked at markers from 25 to 75 year olds. But they didn’t just look at one or two markers like cholesterol or blood sugar, they mapped out thousands of different biological samples from blood samples, stool samples, skin swabs, oral swabs and nasal swabs, so the researchers were able to look at different proteins, metabolites, inflammatory markers, lipids, and even the body’s microbiome over time. This gave them a detailed picture of how whole systems in the body change with age.

The 2019 study, on the other hand, focused specifically on proteins in the blood across people aged 18 to 95. And that’s where they identified a potential third wave of change in the late 70s. It’s not yet confirmed by longer-term tracking, but it gives us important clues about what might be happening later in life.

So let’s break down what the researchers actually did, and what they found.

The 2024 study was a large longitudinal trial, which means they followed people over time. As I just mentioned, they tracked thousands of signals in the body from people aged 25 to 75 years, and this gave them a detailed picture of how different systems in the body shift as we age, our metabolism, immune function, kidney health, and much more.

What they discovered was so very interesting: they discovered that aging doesn’t move in a straight line as we all expect. Instead, the body undergoes two major bursts of change, and potentially a third later in life. In one study, researchers described these shifts as waves of change, while in another they were referred to as crests. Either way, the idea is the same,  instead of aging gradually, our bodies hit sudden turning points where whole systems reorganize. According to this research, the first happens in the early to mid-40s, the second around age 60. 

Then, the 2019 study examined proteins in the blood in people ranging from 18 all the way to 95 years old and saw something similar, but with an extra twist. This study identified not just the midlife and later-life crests—so this data showed changes at 34 and 60, but also a third possible wave of change at around 78 years old. Because it was a cross-sectional study, looking at different people at different ages rather than following the same people over decades, that third wave is more of a hypothesis. Still, it points to another possible turning point, where new proteins and pathways are shifting, especially those linked to cardiovascular health, bone health, and even the brain. And keep in mind this study only looked at proteins in the blood, not the other biological samples. 

But what this interesting data tell us is that aging isn’t a gentle slope downward. It’s more like stepping stones, with big leaps where our biology shifts gears. And for those of us thinking about blood sugar, insulin resistance, or diabetes risk, these leaps matter. Because they happen in the very systems that control how we metabolize carbohydrates, how we handle fat in the blood, and how much inflammation our bodies are carrying. In other words, these waves of change may explain why blood sugar suddenly becomes harder to manage, or why cholesterol and weight seem more stubborn at certain ages.

Let’s start with the first big turning point, in the early to mid-40s.

At this stage, researchers found changes in the way the body handles fats, amino acids, and even substances like caffeine and alcohol. Let’s look a little closer at each of these factors and what the researchers propose is happening. 

Firstly, lipid metabolism, which is how your body processes and transports fats, begins to work less efficiently. Essential fatty acid pathways start to decline, which can affect heart and brain health. With prediabetes or type 2 diabetes, this matters because lipid changes directly influence insulin resistance and cardiovascular risk. When we talk about lipids, we’re talking about cholesterol. Let’s just say if your HDL, that’s your so-called ‘good’ cholesterol, isn’t remodeling well, or if fatty acids aren’t being processed effectively, that can worsen insulin resistance and push your blood sugar and triglycerides in the wrong direction.

In terms of amino acids, the studies found changes in glycine, serine, and threonine metabolism around this age. These amino acids play roles in making glutathione, the body’s master antioxidant, which protects against oxidative stress. They’re also important for metabolic flexibility, which is the ability to switch between burning glucose and fat efficiently. So when these pathways don’t work as well, the result is less effective tissue repair, lower antioxidant protection, and potentially more oxidative stress. For someone already dealing with higher blood sugar or insulin resistance, that can add fuel to the fire, making it harder to recover from stress, exercise, or even day-to-day wear and tear. The researchers didn’t measure muscle directly in this study, but we know from other research that muscle mass naturally starts to decline after 40. So when you put those pieces together, it helps explain why many people in their 40s notice it’s harder to keep muscle on, perhaps this decline in amino acid metabolism influences muscle loss in some way. Regardless, it’s another interesting part of the puzzle that shows us why protecting muscle becomes so critical for blood sugar regulation—muscle is the main place glucose gets disposed of.

Another change that researchers observed around this age is our detoxification pathways can decline, particularly for caffeine and alcohol. Both are cleared by the liver, and the proteins and enzymes responsible for breaking them down start to shift.

With caffeine, this means it lingers longer in your system. You may notice you can’t tolerate that afternoon coffee the way you used to, because it interferes with sleep. And poor sleep isn’t just about feeling tired, it directly reduces insulin sensitivity, increases hunger hormones, and makes blood sugar harder to manage.

With alcohol, slower metabolism means the same glass of wine or beer can have a stronger effect on the liver. That’s important because alcohol metabolism competes with glucose metabolism in the liver. If the liver is busy clearing alcohol, it can’t manage blood sugar as effectively. On top of that, alcohol can raise triglycerides and worsen fatty liver, both of which are already major concerns in type 2 diabetes and prediabetes.

So the combination of these metabolic shifts in lipids, amino acids, caffeine, and alcohol,  give us more clues as to why many people start to notice subtle but very real changes in their 40s. Their blood sugar becomes more stubborn, their energy isn’t quite the same, and things that were once easy to tolerate, like a drink in the evening or a late coffee, suddenly have a bigger impact.

Now let’s look at the second big turning point, the early 60s.

Both studies identified this as a major biological reset. In fact, the changes here were even larger than what happened in the 40s. At this stage, whole networks of proteins and pathways reorganize, especially those tied to carbohydrate metabolism, inflammation, lipid handling, and even kidney function.

In terms of carbohydrate metabolism, researchers saw shifts in proteins that regulate how we process glucose. Essentially, the body becomes less efficient at handling carbohydrates. That means even if your diet hasn’t changed, you may notice your blood sugar creeping higher. For someone with prediabetes or type 2 diabetes, this also helps explain why glucose control may feel even more difficult in your 60s and beyond, compared to a person in their 40s or 50s.

In terms of amino acids and muscle, the research suggests there are also changes in branched-chain amino acid metabolism, that’s valine, leucine, and isoleucine. These are critical for muscle protein synthesis. When this pathway declines, it becomes harder to build and maintain muscle, and muscle loss at this age accelerates. That’s bad news for blood sugar, because less muscle means less glucose disposal.

In terms of lipids and inflammation, just like in the 40s, lipid metabolism continues to shift, but now inflammation becomes a much bigger player. The researchers identified proteins that are tied to atherosclerosis, heart disease and insulin resistance. So the 60s are often when cardiovascular risk and metabolic risk really start to overlap.

In terms of kidney function, another interesting finding was that markers of kidney filtration began to change at this stage. That’s important, because the kidneys play a role in glucose balance and blood pressure regulation. And kidney disease is one of the major long-term complications of diabetes.

So when we zoom out to see the big picture, the second crest, or wave, is really about the body losing efficiency in several critical systems at once: glucose metabolism, inflammation control, muscle preservation, lipid transport, and kidney function. And this is why many people in their 60s notice that health challenges seem to compound, blood sugar is harder to control, weight feels harder to manage, and other conditions like high blood pressure or high cholesterol often start showing up together.

There’s also a possible third wave of change later in life. This one comes from the earlier 2019 Stanford study, which looked at proteins in the blood of people all the way up to age 95. In that research, they saw another surge of change around 78 years old, involving new sets of proteins tied to cardiovascular health, bone health, and even brain function – so some of the health challenges that arise or worsen could reflect this third biological shift. But this late-life wave is still considered more of a hypothesis until further data arises. 

So what does all this research mean for you? Knowing that our bodies don’t age in a smooth, steady line, but instead hit these biological turning points, gives us the chance to prepare and adjust at the right times.

In our 40s, this is when changes in lipid metabolism, amino acid pathways, and detoxification start to appear. 

What this means practically for all of us and especially with prediabetes and type 2 diabetes, is we want to be focusing on building and protecting muscle with resistance training and adequate protein. Support lipid health with healthy fats like olive oil and avocado and omega-3s, while cutting processed seed oils and trans fats. Support your antioxidant defenses by eating a variety of colorful vegetables and considering glycine-rich foods like collagen or bone broth. And be mindful of caffeine and alcohol, smaller amounts can have bigger effects now, especially on sleep and liver health, which can dramatically impact blood glucose control.

In our 60s, the body’s efficiency in multiple systems declines at once, glucose handling, inflammation control, lipid processing, and kidney function. What this means practically is tightening carbohydrate intake, focusing on vegetables, high fiber, and spreading protein across meals. Continuing to prioritize strength and mobility work to slow muscle loss. Add more anti-inflammatory foods such as omega-3 rich fish, colorful produce, herbs and spices. Stay on top of lab checks for blood sugar, cholesterol, and kidney health. Build recovery into your lifestyle. Things like sleep, stress management, and restorative activity become non-negotiables.

In the late 70s – the stage that is still more theoretical but worth nothing. During this stage, keep up physical activity including strength and balance work. Prioritize nutrient-dense foods to support bone and brain health, especially calcium, vitamin D, and omega-3s. Monitor cardiovascular health closely, cholesterol, blood pressure, and inflammation. Support liver health, and stay socially and cognitively engaged, the brain thrives on stimulation and connection.

Now, I’ve very quickly provided some key strategies to think about at these stages, but not all of them, which we don’t have time to go deeper right here and now. If you’re one of our members, we will be providing more specific guidelines to focus on during these phases, some different protocols to try that can help you push past some of the obstacles experienced during this stage. In fact, we’ve got some new and exciting things planned for the new year – I can’t believe I’m even saying the new year, but it is the end of november, and that’s not too far away, wow! Anyway, in the new year, we’ll be providing monthly progress boosters for our VIP Members. These will be like mini challenges and focus tasks that help with positive progress and we know they will be impactful and energizing, so we can’t wait to introduce those. 

But back to today’s topic on these biological shifts. The important thing to take from this research is that while there may be waves of changes that occur in our bodies at certain ages, that doesn’t mean bad health is inevitable. In our 40s there may be lipid and amino acid changes, in our 60s there may be additional changes to the way our body processes nutrients. What this means is we need to be more focused on our health as we age, more committed to quality nutrition, more proactive, which of course makes sense. And with the right strategies, many of which we talk about on this podcast all the time, we can all prepare for these shifts, minimize the challenges and even come out stronger. It is possible, no matter what age, to reverse the status of our health. That’s what I find so fascinating, is the body has an amazing capacity to heal and change when it’s given the right nutrition and support to do so. We’ve certainly seen that with many of our members, who are now in the best health they’ve been in for many many years. 

I hope you enjoyed today’s episode and if you did, please head to our website at Type2DiabetesTalk.com to support the podcast by leaving a 5-star rating and review. I’d really appreciate it. 

Until next time, take care of you.

Dr Jedha, over and out.