The Emperor’s New Klotho, Or Something More?
Exploring how klotho, a gene-associated enzyme, plays a crucial role in aging and might influence treatments for age-related diseases, including Alzheimer’s.
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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Stop Cancer 20 Years Ago
Dr. Jenn Simmons shares vital tips on preventing cancer and inflammation, advocating for lifestyle changes and proactive health management at any age.
Get Abreast And Keep Abreast
This is Dr. Jenn Simmons. Her specialization is integrative oncology, as she—then a breast cancer surgeon—got breast cancer, decided the system wasn’t nearly as good from the patients’ side of things as from the doctors’ side, and took to educate herself, and now others, on how things can be better.
What does she want us to know?
Start now
If you have breast cancer, the best time to start adjusting your lifestyle might be 20 years ago, but the second-best time is now. We realize our readers with breast cancer (or a history thereof) probably have indeed started already—all strength to you.
What this means for those of us without breast cancer (or a history therof) is: start now
Even if you don’t have a genetic risk factor, even if there’s no history of it in your family, there’s just no reason not to start now.
Start what, you ask? Taking away its roots. And how?
Inflammation as the root of cancer
To oversimplify: cancer occurs because an accidentally immortal cell replicates and replicates and replicates and takes any nearby resources to keep on going. While science doesn’t know all the details of how this happens, it is a factor of genetic mutation (itself a normal process, without which evolution would be impossible), something which in turn is accelerated by damage to the DNA. The damage to the DNA? That occurs (often as not) as a result of cellular oxidation. Cellular oxidation is far from the only genotoxic thing out there, and a lot of non-food “this thing causes cancer” warnings are usually about other kinds of genotoxicity. But cellular oxidation is a big one, and it’s one that we can fight vigorously with our lifestyle.
Because cellular oxidation and inflammation go hand-in-hand, reducing one tends to reduce the other. That’s why so often you’ll see in our Research Review Monday features, a line that goes something like:
“and now for those things that usually come together: antioxidant, anti-inflammatory, anticancer, and anti-aging”
So, fight inflammation now, and have a reduced risk of a lot of other woes later.
See: How to Prevent (or Reduce) Inflammation
Don’t settle for “normal”
People are told, correctly but not always helpfully, such things as:
- It’s normal to have less energy at your age
- It’s normal to have a weaker immune system at your age
- It’s normal to be at a higher risk of diabetes, heart disease, etc
…and many more. And these things are true! But that doesn’t mean we have to settle for them.
We can be all the way over on the healthy end of the distribution curve. We can do that!
(so can everyone else, given sufficient opportunity and resources, because health is not a zero-sum game)
If we’re going to get a cancer diagnosis, then our 60s are the decade where we’re most likely to get it. Earlier than that and the risk is extant but lower; later than that and technically the risk increases, but we probably got it already in our 60s.
So, if we be younger than 60, then now’s a good time to prepare to hit the ground running when we get there. And if we missed that chance, then again, the second-best time is now:
See: Focusing On Health In Our Sixties
Fast to live
Of course, anything can happen to anyone at any age (alas), but this is about the benefits of living a fasting lifestyle—that is to say, not just fasting for a 4-week health kick or something, but making it one’s “new normal” and just continuing it for life.
This doesn’t mean “never eat”, of course, but it does mean “practice intermittent fasting, if you can”—something that Dr. Simmons strongly advocates.
See: Intermittent Fasting: We Sort The Science From The Hype
While this calls back to the previous “fight inflammation”, it deserves its own mention here as a very specific way of fighting it.
It’s never too late
All of the advices that go before a cancer diagnosis, continue to stand afterwards too. There is no point of “well, I already have cancer, so what’s the harm in…?”
The harm in it after a diagnosis will be the same as the harm before. When it comes to lifestyle, preventing a cancer and preventing it from spreading are very much the same thing, which is also the same as shrinking it. Basically, if it’s anticancer, it’s anticancer, no matter whether it’s before, during, or after.
Dr. Simmons has seen too many patients get a diagnosis, and place their lives squarely in the hands of doctors, when doctors can only do so much.
Instead, Dr. Simmons recommends taking charge of your health as best you are able, today and onwards, no matter what. And that means two things:
- Knowing stuff
- Doing stuff
So it becomes our responsibility (and our lifeline) to educate ourselves, and take action accordingly.
Want to know more?
We recently reviewed her book, and heartily recommend it:
The Smart Woman’s Guide to Breast Cancer – by Dr. Jenn Simmons
Enjoy!