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:
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Enjoy!
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Easy Ways To Fix Brittle, Dry, Wiry Hair
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Dr. Sam Ellis, a dermatologist, specializes in skin, hair, and nail care—and she’s here with professional knowledge:
Tackling the problem at the root
As we age, hair becomes less shiny, more brittle, coarse, wiry, or gray. More concerningly for many, hair thinning and shedding increases due to shortened growth phases and hormonal changes.
The first set of symptoms there are largely because sebum production decreases, leading to dry hair. It’s worth bearing in mind though, that factors like UV radiation, smoking, stress, and genetics contribute to hair aging too. So while we can’t do much about genetics, the modifiable factors are worth addressing.
Menopause and the corresponding “andropause” impact hair health, and hormonal shifts, not just aging, drive many hair changes. Which is good to know, because it means that HRT (mostly: topping up estrogen or testosterone as appropriate) can make a big difference. Additionally, topical/oral minoxidil and DHT blockers (such as finasteride or dutasteride) can boost hair density. These things come with caveats though, so do research any possible treatment plan before embarking on it, to be sure you are comfortable with all aspects of it—including that if you use minoxidil, while on the one hand it indeed works wonders, on the other hand, you’ll then have to keep using minoxidil for the rest of your life or your hair will fall out when you stop. So, that’s a commitment to be thought through before beginning.
Nutritional deficiencies (iron, zinc, vitamin D) and insufficient protein intake hinder hair growth, so ensure proper nutrition, with sufficient protein and micronutrients.
While we’re on the topic of “from the inside” things: take care to manage stress healthily, as stress negatively affects hair health.
Now, as for “from the outside”…
Dr. Ellis recommends moisturizing shampoos/conditioners; Virtue and Dove brands she mentions positively. She also recommends bond repair products (such as K18 and Olaplex) that restore hair integrity, and heat protectants (she recommends: Unite 7 Seconds) as well as hair oils in general that improve hair condition.
For more on all of this, enjoy:
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Want to learn more?
You might also like to read:
Take care!
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8 Critical Signs Of Blood Clots That You Shouldn’t Ignore
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Blood clots can form as part of deep vein thrombosis or for other reasons; wherever they form (unless they are just doing their job healing a wound) they can cause problems. But how to know what’s going on inside our body?
Telltale signs
Our usual medical/legal disclaimer applies here, and we are not doctors, let alone your doctors, and even if we were we couldn’t diagnose from afar… But for educational purposes, here are the eight signs from the video:
- Swelling: especially if only on one leg (assuming you have no injury to account for it), which may feel tight and uncomfortable
- Warmness: does the area warmer to the touch? This may be because of the body’s inflammatory response trying to deal with a blood clot
- Tenderness: again, caused by the inflammation in response to the clot
- Discolored skin: it could be reddish, or bruise-like. This could be patchy or spread over a larger area, because of a clot blocking the flow of blood
- Shortness of breath: if a clot makes it to the lungs, it can cause extra problems there (pulmonary embolism), and shortness of breath is the first sign of this
- Coughing up blood: less common than the above but a much more serious sign; get thee to a hospital
- Chest pain: a sharp or stabbing pain, in particular. The pain may worsen with deep breaths or coughing. Again, seek medical attention.
For more on recognizing these signs (including helpful visuals), and more on what to do about them and how to avoid them in the first place, enjoy:
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Further reading
You might like to read:
Dietary Changes for Artery Health
Take care!
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Hair-Loss Remedies, By Science
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10almonds Gets Hairy
Hair loss is a thing that at some point affects most men and a large minority of women. It can be a source of considerable dysphoria for both, as it’s often seen as a loss of virility/femininity respectively, and is societally stigmatized in various ways.
Today we’re going to focus on the most common kind: androgenic alopecia, which is called “male pattern baldness” in men and “female pattern baldness” in women, despite being the same thing.
We won’t spend a lot of time on the science of why this happens (we’re going to focus on the remedies instead), but suffice it to say that genes and hormones both play a role, with dihydrogen testosterone (DHT) being the primary villain in this case.
We’ve talked before about the science of 5α-reductase inhibitors to block the conversion of regular testosterone* to DHT, its more potent form:
One Man’s Saw Palmetto Is Another Woman’s Serenoa Repens…
*We all make this to a greater or lesser degree, unless we have had our ovaries/testes removed.
Finasteride
Finasteride is a 5α-reductase inhibitor that performs similarly to saw palmetto, but comes in tiny pills instead of needing to take a much higher dose of supplement (5mg of finasteride is comparable in efficacy to a little over 300mg of saw palmetto).
Does it work? Yes!
Any drawbacks? A few:
- It’ll take 3–6 months to start seeing effects. This is because of the hormonal life-cycle of human hairs.
- Common side-effects include ED.
- It is popularly labelled/prescribed as “only for men”
On that latter point: the warnings about this are severe, detailing how women must not take it, must not even touch it if it has been cut up or crushed.
However… That’s because it can carry a big risk to our unborn fetuses. So, if we are confident we definitely don’t have one of those, it’s not actually applicable to us.
That said, finasteride’s results in women aren’t nearly so clear-cut as in men (though also, there has been less research, largely because of the above). Here’s an interesting breakdown in more words than we have room for here:
Finasteride for Women: Everything You Need to Know
Spironolactone
This one’s generally prescribed to women, not men, largely because it’s the drug sometimes popularly known as a “chemical castration” drug, which isn’t typically great marketing for men (although it can be applied topically, which will have less of an effect on the rest of the body). For women, this risk is simply not an issue.
We’ll be brief on this one, but we’ll just drop this, so that you know it’s an option that works:
❝Spironolactone is an effective and safe treatment of androgenic alopecia which can enhance the efficacy when combined with other conventional treatments such as minoxidil.
Topical spironolactone is safer than oral administration and is suitable for both male and female patients, and is expected to become a common drug for those who do not have a good response to minoxidil❞
Minoxidil
This one is available (to men and women) without prescription. It’s applied topically, and works by shortcutting the hair’s hormonal growth cycle, to reduce the resting phase and kick it into a growth phase.
Does it work? Yes!
Any drawbacks? A few:
- Whereas you’ll remember finasteride takes 3–6 months to see any effect, this one will have an effect very quickly
- Specifically, the immediate effect is: your rate of hair loss will appear to dramatically speed up
- This happens because when hairs are kicked into their growth phase if they were in a resting phase, the first part of that growth phase is to shed each old hair to make room for the new one
- You’ll then need the same 3–6 months as with finasteride, to see the regrowth effects
- If you stop using it, you will immediately shed whatever hair you gained by this method
Why do people choose this over finasteride? For one of three reasons, mainly:
- They are women, and not offered finasteride
- They are men, and do not want the side effects of finasteride
- They just saw an ad and tried it
As to how it works:
Some final notes:
There are some other contraindications and warnings with each of these drugs by the way, so do speak with your doctor/pharmacist. For example:
- Finasteride can tax the liver a little
- Spironolactone can reduce bone turnover
- Minoxidil is a hypotensive; this shouldn’t be an issue for most people, but for some people it could be a problem
There are other hair loss remedies and practices, but the above three are the heavy-hitters, so that’s what we spent our time/space on today. We’ll perhaps cover the less powerful (but less risky) options one of these days.
Meanwhile, take care!
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Freekeh Tomato Feast
10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.
Fiber-dense freekeh stars in this traditional Palestinian dish, and the whole recipe is very gut-healthy, not to mention delicious and filling, as well as boasting generous amounts of lycopene and other phytonutrients:
You will need
- 1 cup dried freekeh (if avoiding gluten, substitute a gluten-free grain, or pseudograin such as buckwheat; if making such a substitution, then also add 1 tbsp nutritional yeast—for the flavor as well as the nutrients)
- 1 medium onion, thinly sliced
- 1 2oz can anchovies (if vegan/vegetarian, substitute 1 can kimchi)
- 1 14oz can cherry tomatoes
- 1 cup halved cherry tomatoes, fresh
- ½ cup black olives, pitted
- 1 5oz jar roasted peppers, chopped
- ½ bulb garlic, thinly sliced
- 2 tsp black pepper
- 1 tsp chili flakes
- 1 sprig fresh thyme
- Extra virgin olive oil
Method
(we suggest you read everything at least once before doing anything)
1) Place a heavy-based (cast iron, if you have it) sauté pan over a medium heat. Add some olive oil, then the onion, stirring for about 5 minutes.
2) Add the anchovies, herbs and spices (including the garlic), and stir well to combine. The anchovies will probably soon melt into the onion; that’s fine.
3) Add the canned tomatoes (but not the fresh), followed by the freekeh, stirring well again to combine.
4) Add 2 cups boiling water, and simmer with the lid on for about 40 minutes. Stir occasionally and check the water isn’t getting too low; top it up if it’s getting dry and the freekeh isn’t tender yet.
5) Add the fresh chopped cherry tomatoes and the chopped peppers from the jar, as well as the olives. Stir for just another 2 minutes, enough to let the latest ingredients warm through.
6) Serve, adding a garnish if you wish:
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
- Why You’re Probably Not Getting Enough Fiber (And How To Fix It)
- Eat More (Of This) For Lower Blood Pressure
- Making Friends With Your Gut (You Can Thank Us Later)
- Lycopene’s Benefits For The Gut, Heart, Brain, & More
- Our Top 5 Spices: How Much Is Enough For Benefits?
Take care!
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The Painkilling Power Of Opioids, Without The Harm?
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When it comes to painkilling medications, they can generally be categorized into two kinds:
- non-opioids (e.g. ibuprofen, paracetamol/acetaminophen, aspirin)
- ones that actually work for something more serious than a headache
That’s an oversimplification, but broadly speaking, when there is serious painkilling to be done, that’s when doctors consider it’s time to break out the opioids.
Nor are all opioids created equal—there’s a noteworthy difference between codeine and morphine, for instance—but the problems of opioids are typically the same (tolerance, addiction, and eventual likelihood of overdose when one tries to take enough to make it work after developing a tolerance), and it becomes simply a matter of degree.
See also: I’ve been given opioids after surgery to take at home. What do I need to know?
So, what’s the new development?
A team of researchers have found that the body can effectively produce its own targetted painkilling peptides, similar in function to benzodiazepines (an opioid drug), but—and which is a big difference—confined to the peripheral nervous system (PNS), meaning that it doesn’t enter the brain.
- The peptides killing the pain before it can reach the brain is obviously good because that means the pain is simply not experienced
- The peptides not having any effect on the brain, however, means that the mechanism of addiction of opioids simply does not apply here
- The peptides not having any effect on the brain also means that the CNS can’t be “put to sleep” by these peptides in the same way it can if a high dose of opioids is taken (this is what typically causes death in opioid overdoses; the heart simply beats too slowly to maintain life)
The hope, therefore, is to now create medications that target the spinal ganglia that produce these peptides, to “switch them on” at will.
Obviously, this won’t happen overnight; there will need to be first a lot of research to find a drug that does that (likely this will involve a lot of trial and error and so many mice/rats), and then multiple rounds of testing to ascertain that the drug is safe and effective for humans, before it can then be rolled out commercially.
But, this is still a big breakthrough; there arguably hasn’t been a breakthrough this big in pain research since various opioid-related breakthroughs in the 70s and 80s.
You can see a pop-science article about it here:
And you can see the previous research (from earlier this year) that this is now building from, about the glial cells in the spinal ganglia, here:
Peripheral gating of mechanosensation by glial diazepam binding inhibitor
But wait, there’s more!
Remember what we said about affecting the PNS without affecting the CNS, to kill the pain without killing the brain?
More researchers are already approaching the same idea to deal with the same problem, but from the angle of gene therapy, and have already had some very promising results with mice:
Structure-guided design of a peripherally restricted chemogenetic system
…which you can read about in pop-science terms (with diagrams!) here:
New gene therapy could alleviate chronic pain, researchers find
While you’re waiting…
In the meantime, approaches that are already available include:
- The 7 Approaches To Pain Management
- Managing Chronic Pain (Realistically!)
- Science-Based Alternative Pain Relief ← when painkillers aren’t helping, these things might!
Take care!
Don’t Forget…
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10 Simple Japanese Habits For Healthier & Longer Life
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You don’t have to be Japanese or live in Okinawa to enjoy the benefits of healthy longevity. A lot of it comes down to simple habits:
Easy to implement
We’ll not keep the 10 habits a mystery; they are:
- Start the day with hot water: drinking hot water in the morning helps with hydration, warming the body, and aiding digestion.
- Enjoy a hearty breakfast: Japanese breakfasts are traditionally filling, nutritious, and help promote energy and longevity. Typical components include rice, miso soup, fish, and pickles.
- Take balanced meals: Japanese education emphasizes nutrition from a young age, promoting balanced meals with proteins, fiber, and vitamins & minerals.
- Enjoy fermented foods: fermented foods, such as nattō and soy-based condiments, support digestion, heart health, and the immune system.
- Drink green tea and matcha: both are rich in health benefits; preparing matcha mindfully adds a peaceful ritual to daily life too.
- Keep the “80% full” rule: “hara hachi bu” encourages eating until 80% full, which can improve longevity and, of course, prevent overeating.
- Use multiple small dishes: small servings and a variety of dishes help prevent overeating and ensure a diverse intake of nutrients.
- Gratitude before and after meals: saying “itadakimasu” and “gochisousama” promotes mindful eating, and afterwards, good digestion. Speaking Japanese is of course not the key factor here, but rather, do give yourself a moment of reflection before and after meals.
- Use vinegar in cooking: vinegar, often used in sushi rice and sauces like ponzu, adds flavor and offers health benefits, mostly pertaining to blood sugar balance.
- Eat slowly: Eating at a slower pace will improve digestion, and can enhance satiety and prevent accidentally overeating.
For more on all of these, enjoy:
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Want to learn more?
You might also like to read:
How To Get More Out Of What’s On Your Plate
Take care!
Don’t Forget…
Did you arrive here from our newsletter? Don’t forget to return to the email to continue learning!
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