
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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The Alzheimer’s Gut-Brain Connection—Caught On X-Ray!
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We’ve written before about Alzheimer’s disease (a lot), and if you’re just joining us, then a great place to start is here:
How To Reduce Your Alzheimer’s Risk
We’ve also written about gut health (a lot), and if you’re just joining us, then a great place to start is here:
Make Friends With Your Gut! (Here’s Why & How)
And as a hat trick, yes, we’ve also written (admittedly not as much) about the gut-brain connection; here’s a primer:
The Brain-Gut Highway: A Two-Way Street
Because of how gut microbes influence brain function, behavior, and cognition, scientists wondered whether one’s microbiome might play a role in Alzheimer’s development. Recently, scientists from Italy’s Institute of Nanotechnology, working with the European Synchrotron Radiation Facility (ESRF), found some concrete answers:
How gut health affects Alzheimer’s
When the gut loses its healthy balance of bacteria, harmful bacteria (and fungi, like C. albicans, also popularly called by its first name, “Candida”) take the wheel. This problem (called “dysbiosis”) allows harmful microbes to produce toxic substances, leading to inflammation and weakening the protective barriers between the gut and brain.
In some cases, like the aforementioned C. albicans, they’ll even put roots through your gut wall (and interact with your nervous system, and they are a common reason for sugar and alcohol cravings—your CNS has literally been hacked by a fungal colony that wants sugar (including the sugar that occurs when alcohol is broken down—and that’s without considering the fact that alcohol also kills several of C. albicans competitors that rank amongst the “good bacteria”). Suffice it to say, the holes it puts in your gut wall aren’t great for the health either.
In any case, once the gut barrier is breached, it’s been hypothesized that harmful bacteria may even travel to the brain, triggering Alzheimer’s.
How the x-rays helped
To better understand gut changes in Alzheimer’s, scientists used a technique called nano- and micro- x-ray phase-contrast tomography (XPCT) at the aforementioned ESRF. That very fancy string of words refers to a commensurately powerful imaging method, which allows researchers to see detailed structures inside the gut without damaging tissue, or even adding contrast agents (like those unpleasant drinks that are sometimes required to be taken before soft-tissue x-rays).
The study examined gut samples from mice with Alzheimer’s (so yes, this does need to be repeated with humans, but in this case there’s no obvious reason why it shouldn’t be the same).
The scans revealed important changes in gut structures, including:
- The tiny finger-like villi and corresponding crypts in the gut lining
- Important cells* that help with digestion and protection
- Neurons involved in gut function
*e.g. Paneth cells, goblet cells, telocytes, and erythrocytes, all of whom would take more explanation than we have room for here, but suffice it to say they’re important to both digestion and correct mucus production (bearing in mind, mucus membranes are one of the main physical barriers to harmful bacteria—as humans, our conscious interactions with mucus are usually only the nuisance that occurs when we get a cold or something, but rest assured, mucus keeps us alive).
In short, all these findings suggest (we’d say “show”, but technically cause and effect have not been proven) gut health indeed plays a crucial role in Alzheimer’s disease pathogenesis and pathology (i.e., how the disease begins and progresses, respectively).
Why it matters
To quote Dr. Alessia Cedola,
❝This technique represents a real breakthrough for the thorough analysis of the gut, and it could be pivotal in early detection and prognosis of the disease.
By gaining a deeper understanding of these processes, we hope to identify new therapeutic targets and develop innovative treatments for this devastating disease.❞
In short: the technology can be used as a super-early diagnostic tool, and ultimately, improve prevention (by encouraging people to focus on gut health) as well as, hopefully, leading to new treatments, too.
Want to see it?
Here’s the paper itself, where there are also abundant very clear images:
Are you on top of your gut health already?
If not, do refer back to that first link we dropped about gut health, up top!
If you are already sure you’re looking after your gut and want to do something else to avoid Alzheimer’s coming to call, you might want to consider:
How To Clean Your Brain (Glymphatic Health Primer) ← your glymphatic system, something many people neglect, is the brain’s cleanup crew, and removes things like the beta-amyloid proteins that are implicated in Alzheimer’s pathogenesis. So, it’s worth knowing how to keep it in working order!
Take care!
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Keep Inflammation At Bay
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How to Prevent (or Reduce) Inflammation
You asked us to do a main feature on inflammation, so here we go!
Before we start, it’s worth noting an important difference between acute and chronic inflammation:
- Acute inflammation is generally when the body detects some invader, and goes to war against it. This (except in cases such as allergic responses) is usually helpful.
- Chronic inflammation is generally when the body does a civil war. This is almost never helpful.
We’ll be tackling the latter, which frees up your body’s resources to do better at the former.
First, the obvious…
These five things are as important for this as they are for most things:
- Get a good diet—the Mediterranean diet is once again a top-scorer
- Exercise—move and stretch your body; don’t overdo it, but do what you reasonably can, or the inflammation will get worse.
- Reduce (or ideally eliminate) alcohol consumption. When in pain, it’s easy to turn to the bottle, and say “isn’t this one of red wine’s benefits?” (it isn’t, functionally*). Alcohol will cause your inflammation to flare up like little else.
- Don’t smoke—it’s bad for everything, and that goes for inflammation too.
- Get good sleep. Obviously this can be difficult with chronic pain, but do take your sleep seriously. For example, invest in a good mattress, nice bedding, a good bedtime routine, etc.
*Resveratrol (which is a polyphenol, by the way), famously found in red wine, does have anti-inflammatory properties. However, to get enough resveratrol to be of benefit would require drinking far more wine than will be good for your inflammation or, indeed, the rest of you. So if you’d like resveratrol benefits, consider taking it as a supplement. Superficially it doesn’t seem as much fun as drinking red wine, but we assure you that the results will be much more fun than the inflammation flare-up after drinking.
About the Mediterranean Diet for this…
There are many causes of chronic inflammation, but here are some studies done with some of the most common ones:
- Beneficial effect of Mediterranean diet in systemic lupus erythematosus patients
- How the Mediterranean diet and some of its components modulate inflammatory pathways in arthritis
- The effects of the Mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease
- Adherence to Mediterranean diet and 10-year incidence of diabetes: correlations with inflammatory and oxidative stress biomarkers*
*Type 1 diabetes is a congenital autoimmune disorder, as the pancreas goes to war with itself. Type 2 diabetes is different, being a) acquired and b) primarily about insulin resistance, and/but this is related to chronic inflammation regardless. It is also possible to have T1D and go on to develop insulin resistance, and that’s very bad, and/but beyond the scope of today’s newsletter, in which we are focusing on the inflammation aspects.
Some specific foods to eat or avoid…
Eat these:
- Leafy greens
- Cruciferous vegetables
- Tomatoes
- Fruits in general (berries in particular)
- Healthy fats, e.g. olives and olive oil
- Almonds and other nuts
- Dark chocolate (choose high cocoa, low sugar)
Avoid these:
- Processed meats (absolute worst offenders are hot dogs, followed by sausages in general)
- Red meats
- Sugar (includes most fruit juices, but not most actual fruits—the difference with actual fruits is they still contain plenty of fiber, and in many cases, antioxidants/polyphenols that reduce inflammation)
- Dairy products (unless fermented, in which case it seems to be at worst neutral, sometimes even a benefit, in moderation)
- White flour (and white flour products, e.g. white bread, white pasta, etc)
- Processed vegetable oils
See also: 9 Best Drinks To Reduce Inflammation, Says Science
Supplements?
Some supplements that have been found to reduce inflammation include:
(links are to studies showing their efficacy)
Consider Intermittent Fasting
Remember when we talked about the difference between acute and chronic inflammation? It’s fair to wonder “if I reduce my inflammatory response, will I be weakening my immune system?”, and the answer is: generally, no.
Often, as with the above supplements and dietary considerations, reducing inflammation actually results in a better immune response when it’s actually needed! This is because your immune system works better when it hasn’t been working in overdrive constantly.
Here’s another good example: intermittent fasting reduces the number of circulating monocytes (a way of measuring inflammation) in healthy humans—but doesn‘t compromise antimicrobial (e.g. against bacteria and viruses) immune response.
See for yourself: Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool ← the study is about the anti-inflammatory effects of fasting
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7 Principles of Becoming a Leader – by Riku Vuorenmaa
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We urge you to overlook the cliché cover art (we don’t know what they were thinking, going for the headless suited torso) because…
This one could be the best investment you make in your career this year! You may be wondering what the titular 7 principles are. We won’t keep you guessing; they are:
- Professional development: personal excellence, productivity, and time management
- Leadership development: mindset and essential leadership skills
- Personal development: your motivation, character, and confidence as a leader
- Career management: plan your career, get promoted and paid well
- Social skills & networking: work and connect with the right people
- Business- & company-understanding: the big picture
- Commitment: make the decision and commit to becoming a great leader
A lot of leadership books repeat the same old fluff that we’ve all read many times before… padded with a lot of lengthy personal anecdotes and generally editorializing fluff. Not so here!
While yes, this book does also cover some foundational things first, it’d be remiss not to. It also covers a whole (much deeper) range of related skills, with down-to-earth, brass tacks advice on putting them into practice.
This is the kind of book you will want to set as a recurring reminder in your phone, to re-read once a year, or whatever schedule seems sensible to you.
There aren’t many books we’d put in that category!
Pick Up Your Copy of the “7 Principles of Becoming a Leader” on Amazon Today!
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Being Mortal – by Dr. Atul Gawande
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Maybe you want to “live forever or die trying”, and that’s an understandable goal… But are you prepared for “or die trying” being the outcome?
This is not a cheerful book, if you’re anything like this reviewer, you will need a little towel or something to mop up the tears while you read. But it’s worth it.
Dying is one thing; fighting for life is even generally considered a noble endeavor. Suffering alone isn’t fun, losing independence can feel humiliating, and seeing someone who was always a tower of strength, now a frail shadow of their former self, reduced to begging for something that they’re “not allowed”, can be worse.
Do we want that for ourselves? For our loved ones? Can there be a happy medium between that, and the alternative to indeed “go gentle into that good night”?
Dr. Gawande, a surgeon well-acquainted with death and dying, thinks so. But it involves work on our part, and being prepared for hard decisions.
- What is most important to us, and what tradeoffs are we willing to make for it?
- What, even, is actually an option to us with the resources available?
- Can we make peace with a potentially bad lot? And… Should we?
- When is fighting important, and when is it self-destructive?
These (and others) are all difficult questions posed by Dr. Gawande, but critical ones.
We don’t usually quote other people’s reviews when reviewing books here, but let’s consider the following words from the end of a long review on Amazon:
❝If “dying as we lived” is some kind of standard for how we should go, then maybe alone and medicalized makes some sense right now after all.❞
Bottom line: we all deserve better than that. And if we don’t take the time to think about what’s most important, then time will take it from us. This very insightful book may not have all the answers, but it has the questions, and it can help a lot in exploring them and deciding what matters most to us in the end, really.
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Coca-Cola vs Diet Coke – Which is Healthier?
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Our Verdict
When comparing Coca-Cola to Diet Coke, we picked the Diet Coke.
Why?
While the Diet Coke is bad, the Coca-Cola has mostly the same problems plus sugar.
The sugar in a can of Coca-Cola is 39g high-fructose corn syrup (the worst kind of sugar yet known to humanity), and of course it’s being delivered in liquid form (the most bioavailable way to get, which in this case, is bad).
To put those 39g into perspective, the daily recommended amount of sugar is 36g for men or 25g for women, according to the AHA.
The sweetener in Diet Coke is aspartame, which has had a lot of health risk accusations made against it, most of which have not stood up to scrutiny, and the main risk it does have is “it mimics sugar too well” and it can increase cravings for sweetness, and therefore higher consumption of sugars in other products. For this reason, the World Health Organization has recommended to simply reduce sugar intake without looking to artificial sweeteners to help.
Nevertheless, aspartame has been found safe (in moderate doses; the upper tolerance level would equate to more than 20 cans of diet coke per day) by food safety agencies ranging from the FDA to the EFSA, based on a large body of science.
Other problems that Diet Coke has are present in Coca-Cola too, such as its acidic nature (bad for tooth enamel) and gassy nature (messes with leptin/ghrelin balance).
Summary: the Diet Coke is relatively less unhealthy, but is still bad in numerous ways, and remains best avoided.
Read more:
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Applesauce vs Cranberry Sauce – Which is Healthier?
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Our Verdict
When comparing applesauce to cranberry sauce, we picked the applesauce.
Why?
It mostly comes down to the fact that apples are sweeter than cranberries:
In terms of macros, they are both equal on fiber (both languishing at a paltry 1.1g/100g), and/but cranberry sauce has 4x the carbs, of which, more than 3x the sugar. Simply, cranberry sauce recipes invariably have a lot of added sugar, while applesauce recipes don’t need that. So this is a huge relative win for applesauce (we say “relative” because it’s still not great, but cranberry sauce is far worse).
In the category of vitamins, applesauce has more of vitamins B1, B2, B5, B6, B9, and C, while cranberry sauce has more of vitamins E, K, and choline. A more moderate win for applesauce this time.
When it comes to minerals, applesauce has more calcium, copper, magnesium, phosphorus, and potassium, while cranberry sauce has more iron, manganese, and selenium. Another moderate win for applesauce.
Since we’ve discussed relative amounts rather than actual quantities, it’s worth noting that neither sauce is a good source of vitamins or minerals, and neither are close to just eating the actual fruits. Just, cranberry sauce is the relatively more barren of the two.
While cranberries famously have some UTI-fighting properties, you cannot usefully gain this benefit from a sauce that (with its very high sugar content and minimal fiber) actively feeds the very C. albicans you are likely trying to kill.
All in all, a pitiful show of nutritional inadequacy from these two products today, but one is relatively less bad than the other, and that’s the applesauce.
Want to learn more?
You might like to read:
From Apples to Bees, and High-Fructose Cs: Which Sugars Are Healthier, And Which Are Just The Same?
Enjoy!
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