How Metformin Slows Aging
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Metformin And How It Slows Down Aging
That’s a bold claim for a title, but the scientific consensus is clear, and this Research Review Monday we’re going to take a look at exactly that!
Metformin is a common diabetes-management drug, used to lower blood sugar levels in people who either don’t have enough insulin or the insulin isn’t being recognized well enough by the body.
However, it also slows aging, which is a quality it’s also been studied for for more than a decade. We’ll look at some of the more recent research, though. Let’s kick off with an initial broad statement, from the paper “The Use of Metformin to Increase the Human Healthspan”, as part of the “Advances in Experimental Medicine and Biology” series:
In recent years, more attention has been paid to the possibility of using metformin as an anti-aging drug. It was shown to significantly increase the lifespan in some model organisms and delay the onset of age-associated declines. Growing amounts of evidence from clinical trials suggest that metformin can effectively reduce the risk of many age-related diseases and conditions, including cardiometabolic disorders, neurodegeneration, chronic inflammation and frailty.
How does it work?
That’s still being studied, but the scientific consensus is that it works by inducing hormesis—the process by which minor stress signals cells to start repairing themselves. How does it induce that hormesis? Again, still being studied, but it appears to do it by activating a specific enzyme; namely, the AMP-activated protein kinase:
Read: Metformin-enhances resilience via hormesis
It also has been found to slow aging by means of an anti-inflammatory effect, as a bonus!
Any bad news?
Well, firstly, in most places it’s only prescribed for diabetes management, not for healthy life extension. A lot of anti-aging enthusiasts have turned to the grey market online to get it, and we can’t recommend that.
Secondly, it does have some limitations:
- Its bioavailability isn’t great in tablet form (the form in which it is most commonly given)
- It has quite a short elimination half-life (around 6 hours), which makes it great to fix transient hyperglycemia in diabetics—job done and it’s out—but presents a logistical challenge when it comes to something so pernicious as aging.
- Some people are non-responders (a non-responder, in medicine, is someone for whom a drug simply doesn’t work, for no obvious reason)
Want to know more? Check out:
Metformin in aging and aging-related diseases: clinical applications and relevant mechanism
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10 Ways To Balance Blood Sugars
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“Let Them Eat Cake”, She Said…
This is Jessie Inchauspé, a French biochemist and author. She’s most known for her best-selling “Glucose Revolution: The Life-Changing Power Of Balancing Your Blood Sugar”.
It’s a great book (which we reviewed recently) and you absolutely should read it, but meanwhile, we’re going to distill at least the most critical core ideas, 10almonds style. In this case, her “ten hacks”:
Eat foods in the right order
The order is:
- Fiber first
- Protein and fat second
- Starches and sugars last
What happens here is… the fiber perks up the gut bacteria, the protein and fat will then be better-digested next, and the starches and sugars will try to jump the line, but they can’t because the fiber is a physical speedbump and the proteins and fats are taking the prime place for being digested. So instead, the starches and sugars—usually responsible for blood sugar spikes—get processed much more gradually, resulting in a nice even curve.
Add a green starter to all your meals
We know what you’re thinking: “that’s just the first one again”, but no. This is an extra starter, before you get to that. If you’re the cook of the household, this can absolutely simply mean snacking on green ingredients while cooking.
Stop counting calories
Especially, she advises: stop worrying about extra calories from fats, such as if doing an oil-and-vinegar dressing for salad—which she also recommends, because all three components (the oil, the vinegar, and the salad) help even out blood sugar levels.
Flatten your breakfast curve
For many, breakfast is the starchiest meal of the day, if not the sugariest. Inchauspé recommends flipping this (ideally) or softening it (if you really must have a carb-based breakfast):
- Top choices include: a warm vegetable salad, fish, or eggs (or tofu if you don’t do animal products).
- Next-best include: if you must have toast, make sure to have butter (and/or the aforementioned egg/tofu, for example) to give your digestion an extra thing to do.
- Also: she recommends skipping the juice in favour of home-made breakfast smoothies. That way, instead of basically just sugar with some vitamins, you’re getting a range of nutrients that, if you stack it right, can constitute a balanced meal itself, with fiber + protein + fat + carbs.
Have any type of sugar—they’re all the same
They’re technically not, but the point is that your body will immediately take them apart and then they will be just the same. Whether it’s the cheapest white sugar or the most expensive organic lovingly hand-reared free-range agave nectar, your body is going to immediately give it the chop-shop treatment (a process so quick as to be practically instantaneous) and say “this is now glucose”.
Pick a dessert over a sweet snack
Remember that about the right order for foods? A dessert, when your body is already digesting dinner, is going to make much less of a glucose spike than, say, a blueberry muffin when all you’ve had this morning is coffee and juice.
Reach for the vinegar before you eat
We recently did a whole main feature about this, so we’ll not double up today!
After you eat, move
The glucose you eat will be used to replace lost muscle glycogen, before any left over is stored as fat… and, while it’s waiting to be stored as fat, just sitting in your bloodstream being high blood sugars. So, this whole thing will go a lot better if you are actively using muscle glycogen (by moving your body).
Inchauspé gives a metaphor: imagine a steam train worker, shoveling coal into the furnace. Meanwhile, other workers are bringing more coal. If the train is moving quickly, the coal can be shoveled into the furnace and burned and won’t build up so quickly. But if the train is moving slowly or not at all, that coal is just going to build up and build up, until the worker can shovel no more because of being neck-deep in coal.
Same with your blood sugars!
If you want to snack, go low-sugar
In the category of advice that will shock nobody: sugary snacks aren’t good for avoiding blood sugar spikes! This one probably didn’t need a chapter devoted to it, but anyway: low sugar is indeed the way to go for snacks.
Put some clothes on your carbs
This is about olive oil on pasta, butter on potatoes, and so forth. Basically, anything starchy is going to be broken down quickly to sugar and sent straight into the bloodstream, if there’s nothing to slow it down. If you’re wondering what to do with rice: adding a tablespoon of chia seeds to the rice while cooking (so they’re cooked together) will add very healthy fats to your rice, and (because they’ve been cooked) will not seem like eating seeds, by the way. In terms of texture and appearance, it’ll be as though you threw some black pepper in*
*which you should also do for many reasons, but that’s beyond the scope of this “about blood sugars” feature!
Wanting to know more about the science of this?
We’ve done all we have room for here today, but Inchauspé is, as ever, happy to explain it herself:
Prefer text? Check out:
The Science Behind Glucose GoddessShare This Post
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Mushrooms vs Eggplant – Which is Healthier?
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Our Verdict
When comparing mushrooms to eggplant, we picked the mushrooms.
Why?
First, you may be wondering: which mushrooms? Button mushrooms? White mushrooms? Chestnut mushrooms? Portobello mushrooms? And the answer is yes. Those (and more; it represents most mushrooms that are commonly sold fresh in western supermarkets) are all the same species at different ages; namely, Agaricus bisporus—not to be mistaken for fly agaric, which despite the name, is not even a member of the Agaricus genus, and is in fact Amanita muscari. This is an important distinction, because fly agaric is poisonous, though fatality is rare, and it’s commonly enjoyed recreationally (after some preparation, which reduces its toxicity) for its psychoactive effects. It’s the famous red one with white spots. Anyway, today we will be talking instead about Agaricus bisporus, which is most popular western varieties of “edible mushroom”.
With that in mind, let’s get down to it:
In terms of macros, mushrooms contain more than 3x the protein, while eggplant contains nearly 2x the carbs and 3x the fiber. We’ll call this a tie for macros.
As for vitamins, mushrooms contain more of vitamins B1, B2, B3, B5, B6, B7, B9, B12, D, and choline, while eggplant contains more of vitamins A, E, and K. Most notably for vegans, mushrooms are a good non-animal source of vitamins B12 and D, which nutrients are not generally found in plants. Mushrooms, of course, are not technically plants. In any case, the vitamins category is an easy win for mushrooms.
When it comes to minerals, mushrooms have more copper, iron, phosphorus, potassium, selenium, and zinc, while eggplant has more calcium, magnesium, and manganese. Another easy win for mushrooms.
One final thing worth noting is that mushrooms are a rich source of the amino acid ergothioneine, which has been called a “longevity vitamin” for its healthspan-increasing effects (see our article below).
Meanwhile, in the category of mushrooms vs eggplant, mushrooms don’t leave much room for doubt and are the clear winner here.
Want to learn more?
You might like to read:
The Magic of Mushrooms: “The Longevity Vitamin” (That’s Not A Vitamin)
Take care!
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Rapamycin Can Slow Aging By 20% (But Watch Out)
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Rapamycin’s Pros & Cons
Rapamycin is generally heralded as a wonderdrug that (according to best evidence so far) can slow down aging, potentially adding decades to human lifespan—and yes, healthspan.
It comes from a kind of soil bacteria, which in turn comes from the island of Rapa Nui (a Chilean territory best known for its monumental moai statues), hence the name rapamycin.
Does it work?
Yes! Probably! With catches!
Like most drugs that are tested for longevity-inducing properties, research in humans is very slow. Of course for drugs in general, they must go through in vitro and in vivo animal testing first before they can progress to human randomized clinical trials, but for longevity-inducing drugs, it’s tricky to even test in humans, without waiting entire human lifetimes for the results.
Nevertheless, mouse studies are promising:
Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
(“Easter Island” is another name given to the island of Rapa Nui)
That’s not a keysmash in the middle there, it’s a reference to rapamycin’s inhibitory effect on the kinase mechanistic target of rapamycin, sometimes called the mammalian target of rapamycin, and either way generally abbreviated to “mTOR”—also known as “FK506-binding protein 12-rapamycin-associated protein 1” or “FRAP1“ to its friends, but we’re going to stick with “mTOR”.
What’s relevant about this is that mTOR regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription.
Don’t those words usually get associated with cancer?
They do indeed! Rapamycin and its analogs have well-demonstrated anti-cancer potential:
❝Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo.
Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer.❞
…and as such, gets used sometimes as an anticancer drug—especially against renal cancer. See also:
Research perspective: Cancer prevention with rapamycin
What’s the catch?
Aside from the fact that its longevity-inducing effects are not yet proven in humans, the mouse models find its longevity effects to be sex-specific, extending the life of male mice but not female ones:
Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects
One hypothesis about this is that it may have at least partially to do with rapamycin’s immunomodulatory effect, bearing in mind that estrogen is immune-enhancing and testosterone is immunosuppressant.
And rapamycin? That’s another catch: it is an immunosuppressant.
This goes in rapamycin’s favor for its use to avoiding rejection when it comes to some transplants (most notably including for kidneys), though the very same immunosuppressant effect is a reason it is contraindicated for certain other transplants (such as in liver or lung transplants), where it can lead to an unacceptable increase in risk of lymphoma and other malignancies:
Prescribing Information: Rapamune, Sirolimus Solution / Sirolimus Tablet
(Sirolimus is another name for rapamycin, and Rapamune is a brand name)
What does this mean for the future?
Researchers think that rapamycin may be able to extend human lifespan to a more comfortable 120–125 years, but acknowledge there’s quite a jump to get there from the current mouse studies, and given the current drawbacks of sex-specificity and immunosuppression:
Advances in anti-aging: Rapamycin shows potential to extend lifespan and improve health
Noteworthily, rapamycin has also shown promise in simultaneously staving off certain diseases associated most strongly with aging, including Alzheimer’s and cardiac disease—or even, starting earlier, to delay menopause, in turn kicking back everything else that has an uptick in risk peri- or post-menopause:
Effect of Rapamycin in Ovarian Aging (Rapamycin)
👆 an upcoming study whose results are thus not yet published, but this is to give an idea of where research is currently at. See also:
Pilot Study Evaluates Weekly Pill to Slow Ovarian Aging, Delay Menopause
Where can I try it?
Not from Amazon, that’s for sure!
It’s still tightly regulated, but you can speak with your physician, especially if you are at risk of cancer, especially if kidney cancer, about potentially being prescribed it as a preventative—they will be able to advise about safety and applicability in your personal case.
Alternatively, you can try getting your name on the list for upcoming studies, like the one above. ClinicalTrials.gov is a great place to watch out for those.
Meanwhile, take care!
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Decoding Hormone Balancing in Ads
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It’s Q&A Time!
This is the bit whereby each week, we respond to subscriber questions/requests/etc
Have something you’d like to ask us, or ask us to look into? Hit reply to any of our emails, or use the feedback widget at the bottom, and a Real Human™ will be glad to read it!
Q: As to specific health topics, I would love to see someone address all these Instagram ads targeted to women that claim “You only need to ‘balance your hormones’ to lose weight, get ripped, etc.” What does this mean? Which hormones are they all talking about? They all seem to be selling a workout program and/or supplements or something similar, as they are ads, after all. Is there any science behind this stuff or is it mostly hot air, as I suspect?
Thank you for asking this, as your question prompted yesterday’s main feature, What Does “Balancing Your Hormones” Even Mean?
That’s a great suggestion also about addressing ads (and goes for health-related things in general, not just hormonal stuff) and examining their claims, what they mean, how they work (if they work!), and what’s “technically true but may
be misleading* cause confusion”*We don’t want companies to sue us, of course.
Only, we’re going to need your help for this one, subscribers!
See, here at 10almonds we practice what we preach. We limit screen time, we focus on our work when working, and simply put, we don’t see as many ads as our thousands of subscribers do. Also, ads tend to be targeted to the individual, and often vary from country to country, so chances are good that we’re not seeing the same ads that you’re seeing.
So, how about we pull together as a bit of a 10almonds community project?
- Step 1: add our email address to your contacts list, if you haven’t already
- Step 2: When you see an ad you’re curious about, select “share” (there is usually an option to share ads, but if not, feel free to screenshot or such)
- Step 3: Send the ad to us by email
We’ll do the rest! Whenever we have enough ads to review, we’ll do a special on the topic.
We will categorically not be able to do this without you, so please do join in—Many thanks in advance!
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Lucid Dreaming – by Stephen LaBerge Ph.D.
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For any unfamiliar: lucid dreaming means being aware that one is dreaming, while dreaming, and exercising a degree of control over the dream. Superficially, this is fun. But if one really wants to go deeper into it, it can be a lot more:
Dr. Stephen LaBerge takes a science-based approach to lucid dreaming, and in this work provides not only step-by-step instructions of several ways of inducing lucid dreaming, but also, opens the reader’s mind to things that can be done there beyond the merely recreational:
In lucid dreams, he argues and illustrates, it’s possible to talk to parts of one’s own subconscious (Inception, anyone? Yes, this book came first) and get quite an amount of self-therapy done. And that hobby you wish you had more time to practice? The possibilities just became limitless. And who wouldn’t want that?
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Healthy Harissa Falafel Patties
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You can make these as regular falafel balls if you prefer, but patties are quicker and easier to cook, and are great for popping in a pitta.
You will need
For the falafels:
- 1 can chickpeas, drained, keep the chickpea water (aquafaba)
- 1 red onion, roughly chopped
- 2 tbsp chickpea flour (also called gram flour or garbanzo bean flour)
- 1 bunch parsley
- 1 tbsp harissa paste
- Extra virgin olive oil for frying
For the harissa sauce:
- ½ cup crème fraîche or plant-based equivalent (you can use our Plant-Based Healthy Cream Cheese recipe and add the juice of 1 lemon)*
- 1 tbsp harissa paste (or adjust this quantity per your heat preference)
*if doing this, rather than waste the zest of the lemon, you can add the zest to the falafels if you like, but it’s by no means necessary, just an option
For serving:
- Wholegrain pitta or other flatbread (you can use our Healthy Homemade Flatbreads recipe)
- Salad (your preference; we recommend some salad leaves, sliced tomato, sliced cucumber, maybe some sliced onion, that sort of thing)
Method
(we suggest you read everything at least once before doing anything)
1) Blend the chickpeas, 1 oz of the aquafaba, the onion, the parsley, and the harissa paste, until smooth. Then add in the chickpea flour until you get a thick batter. If you overdo it with the chickpea flour, add a little more of the aquafaba to equalize. Refrigerate the mixture for at least 30 minutes.
2) Heat some oil in a skillet, and spoon the falafel mixture into the pan to make the patties, cooking on both sides (you can use a spatula to gently turn them), and set them aside.
3) Mix the harissa sauce ingredients in a small bowl.
4) Assemble; best served warm, but enjoy it however you like!
Enjoy!
Want to learn more?
For those interested in more of what we have going on today:
- Why You’re Probably Not Getting Enough Fiber (And How To Fix It)
- Capsaicin For Weight Loss And Against Inflammation
- Hero Homemade Hummus ← another great option
Take care!
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