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❞

~ Dr. Lehrer & Dr. Rheinstein

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):

The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study

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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  • Before You Eat Breakfast: 3 Surprising Facts About Intermittent Fasting

    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.

    Dr. William Li is well-known for his advocacy of “eating to beat disease”, and/but today he has advice for us about not eating to beat disease. In moderation, of course, thus: intermittent fasting.

    The easy way

    Dr. Li explains the benefits of intermittent fasting; how it improves the metabolism and gives the body a chance to do much-needed maintainance, including burning off any excess fat we had hanging around.

    However, rather than calling for us to do anything unduly Spartan, he points out that it’s already very natural for us to fast while sleeping, so we only need to add a couple of hours before and after sleeping (assuming an 8 hour sleep), to make it to a 12-hour fast for close to zero effort and probably no discomfort.

    And yes, he argues that a 12-hour fast is beneficial, and even if 16 hours would be better, we do not need to beat ourselves up about getting to 16; what is more important is sustainability of the practice.

    Dr. Li advocates for flexibility in fasting, and that it should be done by what manner is easiest, rather than trying to stick to something religiously (of course, if you do fast for religious reasons, that is another matter, and/but beyond the scope of this today).

    For more information on each of these, as well as examples and tips, enjoy:

    Click Here If The Embedded Video Doesn’t Load Automatically!

    Want to learn more?

    You might also like to read:

    Take care!

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  • Astaxanthin: Super-Antioxidant & Neuroprotectant

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    Think Pink For Brain Health!

    Astaxanthin is a carotenoid that’s found in:

    • certain marine microalgae
    • tiny crustaceans that eat the algae
    • fish (and flamingos!) that eat the crustaceans

    Yes, it’s the one that makes things pink.

    But it does a lot more than that…

    Super-antioxidant

    Move over, green tea! Astaxanthin has higher antioxidant activity than most carotenoids. For example, it is 2–5 times more effective than alpha-carotene, lutein, beta-carotene, and lycopene:

    Antioxidant activities of astaxanthin and related carotenoids

    We can’t claim credit for naming it a super-antioxidant though, because:

    Astaxanthin: A super antioxidant from microalgae and its therapeutic potential

    Grow new brain cells

    Axtaxanthin is a neuroprotectant, but that’s to be expected from something with such a powerful antioxidant ability.

    What’s more special to astaxanthin is that it assists continued adult neurogenesis (creation of new brain cells):

    ❝The unique chemical structure of astaxanthin enables it to cross the blood-brain barrier and easily reach the brain, where it may positively influence adult neurogenesis.

    Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation.

    By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging. ❞

    Source: Dietary Astaxanthin: A Promising Antioxidant and Anti-Inflammatory Agent for Brain Aging and Adult Neurogenesis

    That first part is very important, by the way! There are so many things that our brain needs, and we can eat, but the molecules are unable to pass the blood-brain barrier, meaning they either get wasted, or used elsewhere, or dismantled for their constituent parts. In this case, it zips straight into the brain instead.

    See also:

    How To Grow New Brain Cells (At Any Age)

    (Probably) good for the joints, too

    First, astaxanthin got a glowing report in a study we knew not to trust blindly:

    A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis

    …and breathe. What a title that was! But, did you catch why it’s not to be trusted blindly? It was down at the bottom…

    ❝Conflict of interest statement

    NOVAREX Co., Ltd. funded the study. Valensa International provided the FlexPro MD® ingredients, and NOVAREX Co., Ltd. encapsulated the test products (e.g., both FlexPro MD® and placebo)❞

    Studies where a supplement company funded the study are not necessarily corrupt, but they can certainly sway publication bias, i.e. the company funds a bunch of studies and then pulls funding from the ones that aren’t going the way it wants.

    So instead let’s look at:

    Astaxanthin attenuates joint inflammation induced by monosodium urate crystals

    and

    Astaxanthin ameliorates cartilage damage in experimental osteoarthritis

    …which had no such conflicts of interest.

    They agree that astaxanthin indeed does the things (attenuates joint inflammation & ameliorates cartilage damage).

    However, they are animal studies (rats), so we’d like to see studies with humans to be able to say for sure how much it helps these things.

    Summary of benefits

    Based on the available research, astaxanthin…

    • is indeed a super-antioxidant
    • is a neuroprotective agent
    • also assists adult neurogenesis
    • is probablygood for joints too

    How much do I take, and is it safe?

    A 2019 safety review concluded:

    ❝Recommended or approved doses varied in different countries and ranged between 2 and 24 mg.

    We reviewed 87 human studies, none of which found safety concerns with natural astaxanthin supplementation, 35 with doses ≥12 mg/day.❞

    Source: Astaxanthin: How much is too much? A safety review

    In short: for most people, it’s very safe and well-tolerated. If you consume it to an extreme, you will likely turn pink, much as you would turn orange if you did the same thing with carrots. But aside from that, the risks appear to be minimal.

    However! If you have a seafood allergy, please take care to get a supplement that’s made from microalgae, not one that’s made from krill or other crustaceans, or from other creatures that eat those.

    Where can I get it?

    We don’t sell it, but here’s an example product on Amazon, for your convenience

    Enjoy!

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  • I Contain Multitudes – by Ed Yong

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    A little while back we reviewed a book (Planet of Viruses) about the role of viruses in our lives, beyond the obvious. Today’s book gives the same treatment to microbes in general—mostly bacteria.

    We all know about pathogens, and we all know about gut microbiota and that some (hopefully the majority) there are good for our health. This book covers those things too, but also much more.

    Pulitzer Prize-winning science writer Ed Yong takes a big picture view (albeit, of some very small things) and looks at the many ways microbes keep us alive, directly or indirectly. From the microbes that convert certain proteins in breast milk into a form that babies can digest (yes, this means we produce nutrients in breast milk that have been evolved solely to feed that bacterium), to those without which agriculture would simply not work, we’re brought to realize how much our continued existence is contingent on our trillions of tiny friends.

    The style throughout is easy-reading pop-science, very accessible. There’s also plenty in terms of practical take-away value, when it comes to adjusting our modern lives to better optimize the benefits we get from microbes—inside and out.

    Bottom line: if you’d like to learn about the role of microbes in our life beyond “these ones are pathogens” and “these ones help our digestion”, this is the book for you.

    Click here to check out I Contain Multitudes, and learn more about yours and those around you!

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  • Skin Care Down There (Incl. Butt Acne, Hyperpigmentation, & More)

    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.

    Dr. Sam Ellis, dermatologist, gives us the low-down:

    Where the sun don’t shine

    Common complaints and remedies that Dr. Ellis covers in this video include:

    • Butt acne/folliculitis: most butt breakouts are actually folliculitis, not traditional acne. Folliculitis is caused by friction, sitting for long periods, or wearing tight clothes. Solutions include antimicrobial washes like benzoyl peroxide and changing sitting habits (i.e. to sit less)
    • Keratosis pilaris: rough bumps around hair follicles can appear on the butt, often confused with acne.
    • Boils and abscesses: painful, large lumps; these need medical attention for drainage.
    • Hidradenitis suppurativa: recurrent painful cysts and boils in skin creases, often in the groin and buttocks. These require medical intervention and treatment.
    • Ingrown hairs: are common in people who shave or wax. Treat with warm compresses and gentle exfoliants.
    • Hyperpigmentation: is often caused by hormonal changes, friction, or other irritation. Laser hair removal and gentle chemical exfoliants can help.

    In the event that the sun does, in fact, shine on your genitals (for example you sunbathe nude and have little or no pubic hair), then sun protection is essential to prevent further darkening (and also, incidentally, reduce the risk of cancer).

    For more on all of this, plus a general introduction to skincare in the bikini zone (i.e. if everything’s fine there right now and you’d like to keep it that way), enjoy:

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    Want to learn more?

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    Take care!

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  • Why is cancer called cancer? We need to go back to Greco-Roman times for the answer

    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.

    One of the earliest descriptions of someone with cancer comes from the fourth century BC. Satyrus, tyrant of the city of Heracleia on the Black Sea, developed a cancer between his groin and scrotum. As the cancer spread, Satyrus had ever greater pains. He was unable to sleep and had convulsions.

    Advanced cancers in that part of the body were regarded as inoperable, and there were no drugs strong enough to alleviate the agony. So doctors could do nothing. Eventually, the cancer took Satyrus’ life at the age of 65.

    Cancer was already well known in this period. A text written in the late fifth or early fourth century BC, called Diseases of Women, described how breast cancer develops:

    hard growths form […] out of them hidden cancers develop […] pains shoot up from the patients’ breasts to their throats, and around their shoulder blades […] such patients become thin through their whole body […] breathing decreases, the sense of smell is lost […]

    Other medical works of this period describe different sorts of cancers. A woman from the Greek city of Abdera died from a cancer of the chest; a man with throat cancer survived after his doctor burned away the tumour.

    Where does the word ‘cancer’ come from?

    Galen, the physician
    Why does the word ‘cancer’ have its roots in the ancient Greek and Latin words for crab? The physician Galen offers one explanation. Pierre Roche Vigneron/Wikimedia

    The word cancer comes from the same era. In the late fifth and early fourth century BC, doctors were using the word karkinos – the ancient Greek word for crab – to describe malignant tumours. Later, when Latin-speaking doctors described the same disease, they used the Latin word for crab: cancer. So, the name stuck.

    Even in ancient times, people wondered why doctors named the disease after an animal. One explanation was the crab is an aggressive animal, just as cancer can be an aggressive disease; another explanation was the crab can grip one part of a person’s body with its claws and be difficult to remove, just as cancer can be difficult to remove once it has developed. Others thought it was because of the appearance of the tumour.

    The physician Galen (129-216 AD) described breast cancer in his work A Method of Medicine to Glaucon, and compared the form of the tumour to the form of a crab:

    We have often seen in the breasts a tumour exactly like a crab. Just as that animal has feet on either side of its body, so too in this disease the veins of the unnatural swelling are stretched out on either side, creating a form similar to a crab.

    Not everyone agreed what caused cancer

    Bust of physician Erasistratus
    The physician Erasistratus didn’t think black bile was to blame. Didier Descouens/Musée Ingres-Bourdelle/Wikimedia, CC BY-SA

    In the Greco-Roman period, there were different opinions about the cause of cancer.

    According to a widespread ancient medical theory, the body has four humours: blood, yellow bile, phlegm and black bile. These four humours need to be kept in a state of balance, otherwise a person becomes sick. If a person suffered from an excess of black bile, it was thought this would eventually lead to cancer.

    The physician Erasistratus, who lived from around 315 to 240 BC, disagreed. However, so far as we know, he did not offer an alternative explanation.

    How was cancer treated?

    Cancer was treated in a range of different ways. It was thought that cancers in their early stages could be cured using medications.

    These included drugs derived from plants (such as cucumber, narcissus bulb, castor bean, bitter vetch, cabbage); animals (such as the ash of a crab); and metals (such as arsenic).

    Galen claimed that by using this sort of medication, and repeatedly purging his patients with emetics or enemas, he was sometimes successful at making emerging cancers disappear. He said the same treatment sometimes prevented more advanced cancers from continuing to grow. However, he also said surgery is necessary if these medications do not work.

    Surgery was usually avoided as patients tended to die from blood loss. The most successful operations were on cancers of the tip of the breast. Leonidas, a physician who lived in the second and third century AD, described his method, which involved cauterising (burning):

    I usually operate in cases where the tumours do not extend into the chest […] When the patient has been placed on her back, I incise the healthy area of the breast above the tumour and then cauterize the incision until scabs form and the bleeding is stanched. Then I incise again, marking out the area as I cut deeply into the breast, and again I cauterize. I do this [incising and cauterizing] quite often […] This way the bleeding is not dangerous. After the excision is complete I again cauterize the entire area until it is dessicated.

    Cancer was generally regarded as an incurable disease, and so it was feared. Some people with cancer, such as the poet Silius Italicus (26-102 AD), died by suicide to end the torment.

    Patients would also pray to the gods for hope of a cure. An example of this is Innocentia, an aristocratic lady who lived in Carthage (in modern-day Tunisia) in the fifth century AD. She told her doctor divine intervention had cured her breast cancer, though her doctor did not believe her.

    Ancient city of Carthage
    Innocentia from Carthage, in modern-day Tunisia, believed divine intervention cured her breast cancer. Valery Bareta/Shutterstock

    From the past into the future

    We began with Satyrus, a tyrant in the fourth century BC. In the 2,400 years or so since then, much has changed in our knowledge of what causes cancer, how to prevent it and how to treat it. We also know there are more than 200 different types of cancer. Some people’s cancers are so successfully managed, they go on to live long lives.

    But there is still no general “cure for cancer”, a disease that about one in five people develop in their lifetime. In 2022 alone, there were about 20 million new cancer cases and 9.7 million cancer deaths globally. We clearly have a long way to go.

    Konstantine Panegyres, McKenzie Postdoctoral Fellow, Historical and Philosophical Studies, The University of Melbourne

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • How Does Fat Actually Leave The Body? Where Does It Go?

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    Fat loss is often misunderstood, with many believing it simply “vanishes” through exercise, is simply excreted in solid form in the bathroom, or materially disappears when converted for energy. However, the principle of conservation of mass plays out here, in that the mass in fat doesn’t disappear—it changes its arrangement:

    In and out

    Fat is composed of carbon, hydrogen, and oxygen atoms, with an example common form of fat in the body being C55H104O6. That’s a lot of Cs and Hs, and a few Os.

    When fat leaves the body, it has been primarily converted into carbon dioxide (CO2) and water (H2O).

    According to a 2014 study by the University of South Wales, 84% of the mass of fat exits the body as CO2 exhaled through breathing, while 16% leaves as water through sweat, urine, and other bodily fluids (all of which contain H2O).

    You’ll notice there are a lot more Os going out, proportionally, than we originally had in the C55H104O6. For this reason, the process requires oxygen intake; for every 10 kilograms of fat burned, by simple mathematics the body needs around 29 kilograms of oxygen.

    Physical activity plays a crucial role in fat loss. When the body exerts itself, it naturally switches to a higher oxygen metabolism necessary for fat breakdown. This effect is amplified during intermittent fasting, which boosts human growth hormone (HGH), a hormone that aids in fat metabolism.

    However, simply hyperventilating won’t work; exercise is essential to activate these processes—otherwise it’s just a case of oxygen in, oxygen out, without involving the body’s chemical energy reserves.

    Consequently, one of the best diet-and-exercise combinations for fat loss is intermittent fasting with high-intensity interval training.

    And, as for what to eat, this video says raw vegan, but honestly, that’s not scientific consensus. However, a diet rich in unprocessed (or minimally processed) fruits and vegetables definitely is where it’s at, with the plant-heavy Mediterranean diet generally scoring highest—which can be further improved by skipping the mammals to make it pesco-Mediterranean. Current scientific consensus does not give any extra benefits for also omitting moderate consumption of fish and fermented dairy products, so include those if you want, or skip those if you prefer.

    For more on all of this, enjoy:

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    Are You A Calorie-Burning Machine? (Calorie Mythbusting)

    Take care!

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