The Emperor’s New Klotho, Or Something More?
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Unzipping The Genes Of Aging?
Klotho is an enzyme encoded in humans’ genes—specifically, in the KL gene.
It’s found throughout all living parts of the human body (and can even circulate about in its hormonal form, or come to rest in its membranaceous form), and its subgroups are especially found:
- α-klotho: in the brain
- β-klotho: in the liver
- γ-klotho: in the kidneys
Great! Why do we care?
Klotho, its varieties and variants, its presence or absence, are very important in aging.
Almost every biological manifestation of aging in humans has some klotho-related indicator; usually the decrease or mutation of some kind of klotho.
Which way around the cause and effect go has been the subject of much debate and research: do we get old because we don’t have enough klotho, or do we make less klotho because we’re getting old?
Of course, everything has to be tested per variant and per system, so that can take a while (punctuated by research scientists begging for more grants to do the next one). Given that it’s about aging, testing in humans would take an incredibly long while, so most studies so far have been rodent studies.
The general gist of the results of rodent studies is “reduced klotho hastens aging; increased klotho slows it”.
(this can be known by artificially increasing or decreasing the level of klotho expression, again something easier in mice as it is harder to arrange transgenic humans for the studies)
Here’s one example of many, of that vast set of rodent studies:
Suppression of Aging in Mice by the Hormone Klotho
Relevance for Alzheimer’s, and a science-based advice
A few years ago (2020), an Alzheimer’s study was undertaken; they noted that the famous apolipoprotein E4 (apoE4) allele is the strongest genetic risk factor for Alzheimer’s, and that klotho may be another. FGF21 (secreted by the liver, mostly during fasting) binds to its own receptor (FGFR1) and its co-receptor β-klotho. Since this is a known neuroprotective factor, they wondered whether klotho itself may interact with β-amyloid (Aβ), and found:
❝Aβ can enhance the ability of klotho to draw FGF21 to regions of incipient neurodegeneration in AD❞
In other words: β-amyloid, the substance whose accumulation is associated with neurodegeneration in Alzheimer’s disease, is a mediator in klotho bringing a known neuroprotective factor, FGF21, to the areas of neurodegeneration
In fewer words: klotho calls the firefighters to the scene of the fire
Read more: Alignment of Alzheimer’s disease amyloid β-peptide and klotho
The advice based on this? Consider practicing intermittent fasting, if that is viable for you, as it will give your liver more FGF21-secreting time, and the more FGF21, the more firefighters arrive when klotho sounds the alarm.
See also: Intermittent Fasting: What’s the truth?
…and while you’re at it:
Does intermittent fasting have benefits for our brain?
A more recent (2023) study with a slightly different (but connected) purpose, found results consistent with this:
Longevity factor klotho enhances cognition in aged nonhuman primates
…and, for that matter this (2023) study that found:
Associations between klotho and telomere biology in high stress caregivers
…which looks promising, but we’d like to see it repeated with a sounder method (they sorted caregiving into “high-stress” and “low-stress” depending on whether a child was diagnosed with ASD or not, which is by no means a reliable way of sorting this). They did ask for reported subjective stress levels, but to be more objective, we’d like to see clinical markers of stress (e.g. cortisol levels, blood pressure, heart rate changes, etc).
A very recent (April 2024) study found that it has implications for more aspects of aging—and this time, in humans (but using a population-based cohort study, rather than lab conditions):
Can I get it as a supplement?
Not with today’s technology and today’s paucity of clinical trials, you can’t. Maybe in the future!
However… The presence of senescent (old, badly copied, stumbling and staggering onwards when they should have been killed and eaten and recycled already) cells actively reduces klotho levels, which means that taking supplements that are senolytic (i.e., that kill those senescent cells) can increase serum klotho levels:
Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans
Ok, what can I take for that?
We wrote about a senolytic supplement that you might enjoy, recently:
Fisetin: The Anti-Aging Assassin
Want to know more?
If you have the time, Dr. Peter Attia interviews Dr. Dena Dubal (researcher in several of the above studies) here:
Click Here If The Embedded Video Doesn’t Load Automatically
Enjoy!
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The Dopa-Bean
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Mucuna pruriens, also called the “magic velvet bean”, is an established herbal drug used for the management of male infertility, nervous disorders, and also as an aphrodisiac:
The Magic Velvet Bean of Mucuna pruriens
How it works is more interesting than that, though.
It’s about the dopamine
M. pruriens contains levodopa (L-dopa). That’s right, the same as the dopaminergic medication most often prescribed for Parkinson’s disease. Furthermore, it might even be better than synthetic L-dopa, because:
❝M. pruriens seed extract demonstrated acetylcholinesterase inhibitory activity, while synthetic L-dopa enhanced the activity of the enzyme. It can be concluded that the administration of M. pruriens seed might be effective in protecting the brain against neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases.
M. pruriens seed extract containing L-dopa has shown less acetylcholinesterase activity stimulation compared with L-dopa, suggesting that the extract might have a superior benefit for use in the treatment of Parkinson’s disease.❞
~ Dr. Narisa Kamkaen et al.
Indeed, it has been tested specifically in (human!) Parkinson’s disease patients, which RCT found:
❝The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of l-dopa might possess advantages over conventional l-dopa preparations in the long term management of Parkinson’s disease❞
~ Dr. Regina Katzenschlager et al.
Read more: Mucuna pruriens in Parkinson’s disease: a double-blind clinical and pharmacological study
Beyond Parkinson’s disease
M. pruriens has also been tested and found beneficial in cases of disease other than Parkinson’s, thus:
Mucuna pruriens in Parkinson’s and in some other diseases: recent advancement and future prospective
…but the science is less well-established for things not generally considered related to dopamine, such as cancer, diabetes, and cardiometabolic disorders.
Note, however, that the science for it being neuroprotective is rather stronger.
Against depression
Depression can have many causes, and (especially on a neurological level) diverse presentations. As such, sometimes what works for one person’s depression won’t touch another person’s, because the disease and treatment are about completely different neurotransmitter dysregulations. So, if a person’s depression is due to a shortage of serotonin, for example, then perking up the dopamine won’t help much, and vice versa. See also:
Antidepressants: Personalization Is Key!
When it comes to M. pruriens and antidepressant activity, then predictably it will be more likely to help if your depression is due to too little dopamine. Note that this means that even if your depression is dopamine-based, but the problem is with your dopamine receptors and not the actual levels of dopamine, then this may not help so much, depending on what else you have going on in there.
The science for M. pruriens and depression is young, and we only found non-human animal studies so far, for example:
In summary
It’s good against Parkinson’s in particular and is good against neurodegeneration in general.
It may be good against depression, depending on the kind of depression you have.
Is it safe?
That’s a great question! And the answer is: it depends. For most people, in moderation, it should be fine (but, see our usual legal/medical disclaimer). Definitely don’t take it if you have bipolar disorder or any kind of schizoid/psychotic disorder; it is likely to trigger a manic/psychotic episode if you do.
For more on this, we discussed it (pertaining to L-dopa in general, not M. pruriens specifically) at greater length here:
An Accessible New Development Against Alzheimer’s ← scroll down to the heading that reads “Is there a catch?”
Want to try some?
We don’t sell it, but here for your convenience is an example product on Amazon 😎
Enjoy!
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Feel Great, Lose Weight – by Dr. Rangan Chatterjee
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We all know that losing weight sustainably tends to be harder than simply losing weight. We know that weight loss needs to come with lifestyle change. But how to get there?
One of the biggest problems that we might face while trying to lose weight is that our “metabolic thermostat” has got stuck at the wrong place. Trying to move it just makes our bodies think we are starving, and everything gets even worse. We can’t even “mind over matter” our way through it with willpower, because our bodies will do impressive things on a cellular level in an attempt to save us… Things that are as extraordinary as they are extraordinarily unhelpful.
Dr. Rangan Chatterjee is here to help us cut through that.
In this book, he covers how our metabolic thermostat got stuck in the wrong place, and how to gently tease it back into a better position.
Some advices won’t be big surprises—go for a whole foods diet, avoiding processed food, for example. Probably not a shocker.
Others are counterintuitive, but he explains how they work—exercising less while moving more, for instance. Sounds crazy, but we assure you there’s a metabolic explanation for it that’s beyond the scope of this review. And there’s plenty more where that came from, too.
Bottom line: if your weight has been either slowly rising, or else very stable but at a higher point than you’d like, Dr. Chatterjee can help you move the bar back to where you want it—and keep it there.
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Foot Drop!
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It’s Q&A Day at 10almonds!
Have a question or a request? We love to hear from you!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
❝Interesting about DVT after surgery. A friend recently got diagnosed with foot drop. Could you explain that? Thank you.❞
First, for reference, the article about DVT after surgery was:
DVT Risk Management Beyond The Socks
As for foot drop…
Foot drop is descriptive of the main symptom: the inability to raise the front part of the foot due to localized weakness/paralysis. Hence, if a person with foot drop dangles their feet over the edge of the bed, for example, the affected foot will simply flop down, while the other (if unaffected) can remain in place under its own power. The condition is usually neurological in origin, though there are various more specific causes:
When walking unassisted, this will typically result in a distinctive “steppage gait”, as it’s necessary to lift the foot higher to compensate, or else the toes will scuff along the ground.
There are mobility aids that can return one’s walking to more or less normal, like this example product on Amazon.
Incidentally, the above product will slightly shorten the lifespan of shoes, as it will necessarily pull a little at the front.
There are alternatives that won’t like this example product on Amazon, but this comes with the different problem that it limits the user to stepping flat-footedly, which is not only also not an ideal gait, but also, will serve to allow any muscles down there that were still (partially or fully) functional to atrophy. For this reason, we’d recommend the first product we mentioned over the second one, unless your personal physiotherapist or similar advises otherwise (because they know your situation and we don’t).
Both have their merits, though:
Trends and Technologies in Rehabilitation of Foot Drop: A Systematic Review
Of course, prevention is better than cure, so while some things are unavoidable (especially when it comes to neurological conditions), we can all look after our nerve health as well as possible along the way:
Peripheral Neuropathy: How To Avoid It, Manage It, Treat It
…as well as the very useful:
What Does Lion’s Mane Actually Do, Anyway?
…which this writer personally takes daily and swears by (went from frequent pins-and-needles to no symptoms and have stayed that way, and that’s after many injuries over the years).
If you’d like a more general and less supplements-based approach though, check out:
Steps For Keeping Your Feet A Healthy Foundation
Take care!
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Black Coffee vs Orange Juice – Which is Healthier?
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Our Verdict
When comparing black coffee to orange juice, we picked the coffee.
Why?
While this one isn’t a very like-for-like choice, it’s a choice often made, so it bears examining.
In favor of the orange juice, it has vitamins A and C and the mineral potassium, while the coffee contains no vitamins or minerals beyond trace amounts.
However, to offset that: drinking juice is one of the worst ways to consume sugar; the fruit has not only been stripped of its fiber, but also is in its most readily absorbable state (liquid), meaning that this is going to cause a blood sugar spike, which if done often can lead to insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, and more. Now, the occasional glass of orange juice (and resultant blood sugar spike) isn’t going to cause disease by itself, but everything we consume tips the scales of our health towards wellness or illness (or sometimes both, in different ways), and in this case, juice has a rather major downside that ought not be ignored.
In favor of the coffee, it has a lot of beneficial phytochemicals (mostly antioxidant polyphenols of various kinds), with no drawbacks worth mentioning unless you have a pre-existing condition of some kind.
Coffee can of course be caffeinated or decaffeinated, and we didn’t specify which here. Caffeine has some pros and cons that at worst, balance each other out, and whether or not it’s caffeinated, there’s nothing in coffee to offset the beneficial qualities of the antioxidants we mentioned before.
Obviously, in either case we are assuming consuming in moderation.
In short:
- orange juice has negatives that at least equal, if not outweigh, its positives
- coffee‘s benefits outweigh any drawbacks for most people
Want to learn more?
You might like to read:
- The Bitter Truth About Coffee (or is it?)
- Caffeine: Cognitive Enhancer Or Brain-Wrecker?
- Which Sugars Are Healthier, And Which Are Just The Same?
Take care!
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Ikigai – by Héctor García and Francesc Miralles
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Ikigai is the Japanese term for what in English we often call “raison d’être”… in French, because English is like that.
But in other words: ikigai is one’s purpose in life, one’s reason for living.
The authors of this work spend some chapters extolling the virtues of finding one’s ikigai, and the health benefits that doing so can convey. It is, quite clearly, an important and relevant factor.
The rest of the book goes beyond that, though, and takes a holistic look at why (and how) healthy longevity is enjoyed by:
- Japanese people in general,
- Okinawans in particular,
- Residents of Okinawa’s “blue zone” village with the highest percentage of supercentenarians, most of all.
Covering considerations from ikigai to diet to small daily habits to attitudes to life, we’re essentially looking at a blueprint for healthy longevity.
For a book whose title and cover suggests a philosophy-heavy content, there’s a lot of science in here too, by the way! From microbiology to psychiatry to nutrition science to cancer research, this book covers all bases.
In short: this book gives a lot of good science-based suggestions for adjustments we can make to our lives, without moving to an Okinawan village!
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How Your Exercise Today Gives A Brain Boost Tomorrow
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Regular 10almonds readers may remember we not long back wrote about a study that showed how daily activity levels, in aggregate, make a difference to brain health over the course of 1–2 weeks (in fact, it was a 9-day study):
Daily Activity Levels & The Measurable Difference They Make To Brain Health
Today, we’re going to talk about a new (published today, at time of writing) study that shows the associations between daily exercise levels (amongst other things) and how well people performed in cognitive tests the next day.
By this we mean: they recorded exercise vs sedentary behavior vs sleep on a daily basis (using wearable tech to track it), and tested them daily with cognitive tests, and looked at how the previous day’s activities (or lack thereof) impacted the next day’s test results.
Notably, the sample was of older adults (aged 50–83). The sample size wasn’t huge but was statistically significant (n=76) and the researchers are of course calling for more studies to be done with more people.
What they found
To put their findings into few words:
- Consistent light exercise boosts general cognitive performance not just for hours (which was already known) but through the next day.
- More moderate or vigorous activity than usual in particular led to better working memory and episodic memory the next day.
- More sleep (especially slow-wave deep sleep) improved episodic memory and psychomotor speed.
- Sedentary behavior was associated with poorer working memory.
Let’s define some terms:
- general cognitive performance = average of scores across the different tests
- working memory = very short term memory, such as remembering what you came into this room for, or (as an example of a test format) being able to take down a multi-digit number in one go without it being broken down (and then, testing with longer lengths of number until failure)
- episodic memory = memory of events in a narrative context, where and when they happened, etc
- psychomotor speed = the speed of connection between perception and reaction in quick-response tests
These are, of course, all useful things to have, which means the general advice here is to:
- move more, generally
- exercise more, specifically
- sit less, whenever reasonably possible
- sleep well
You can read the study itself here:
Want to know the best kind of exercise for brain health?
Check out our article about neuroscientist Dr. Suzuki, and what she has to say about it:
The Exercise That Protects Your Brain
Enjoy!
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