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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How Science News Outlets Can Lie To You (Yes, Even If They Cite Studies!)
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Each Monday, we’re going to be bringing you cutting-edge research reviews to not only make your health and productivity crazy simple, but also, constantly up-to-date.
But today, in this special edition, we want to lay out plain and simple how to see through a lot of the tricks used not just by popular news outlets, but even sometimes the research publications themselves.
That way, when we give you health-related science news, you won’t have to take our word for it, because you’ll be able to see whether the studies we cite really support the claims we make.
Of course, we’ll always give you the best, most honest information we have… But the point is that you shouldn’t have to trust us! So, buckle in for today’s special edition, and never have to blindly believe sci-hub (or Snopes!) again.
The above now-famous Tumblr post that became a meme is a popular and obvious example of how statistics can be misleading, either by error or by deliberate spin.
But what sort of mistakes and misrepresentations are we most likely to find in real research?
Spin Bias
Perhaps most common in popular media reporting of science, the Spin Bias hinges on the fact that most people perceive numbers in a very “fuzzy logic” sort of way. Do you?
Try this:
- A million seconds is 11.5 days
- A billion seconds is not weeks, but 13.2 months!
…just kidding, it’s actually nearly thirty-two years.
Did the months figure seem reasonable to you, though? If so, this is the same kind of “human brains don’t do large numbers” problem that occurs when looking at statistics.
Let’s have a look at reporting on statistically unlikely side effects for vaccines, as an example:
- “966 people in the US died after receiving this vaccine!” (So many! So risky!)
- “Fewer than 3 people per million died after receiving this vaccine!” (Hmm, I wonder if it is worth it?)
- “Half of unvaccinated people with this disease die of it” (Oh)
How to check for this: ask yourself “is what’s being described as very common really very common?”. To keep with the spiders theme, there are many (usually outright made-up) stats thrown around on social media about how near the nearest spider is at any given time. Apply this kind of thinking to medical conditions.. If something affects only 1% of the population (So few! What a tiny number!), how far would you have to go to find someone with that condition? The end of your street, perhaps?
Selection/Sampling Bias
Diabetes disproportionately affects black people, but diabetes research disproportionately focuses on white people with diabetes. There are many possible reasons for this, the most obvious being systemic/institutional racism. For example, advertisements for clinical trial volunteer opportunities might appear more frequently amongst a convenient, nearby, mostly-white student body. The selection bias, therefore, made the study much less reliable.
Alternatively: a researcher is conducting a study on depression, and advertises for research subjects. He struggles to get a large enough sample size, because depressed people are less likely to respond, but eventually gets enough. Little does he know, even the most depressed of his subjects are relatively happy and healthy compared with the silent majority of depressed people who didn’t respond.
See This And Many More Educational Cartoons At Sketchplanations.com!
How to check for this: Does the “method” section of the scientific article describe how they took pains to make sure their sample was representative of the relevant population, and how did they decide what the relevant population was?
Publication Bias
Scientific publications will tend to prioritise statistical significance. Which seems great, right? We want statistically significant studies… don’t we?
We do, but: usually, in science, we consider something “statistically significant” when it hits the magical marker of p=0.05 (in other words, the probability of getting that result is 1/20, and the results are reliably coming back on the right side of that marker).
However, this can result in the clinic stopping testing once p=0.05 is reached, because they want to have their paper published. (“Yay, we’ve reached out magical marker and now our paper will be published”)
So, you can think of publication bias as the tendency for researchers to publish ‘positive’ results.
If it weren’t for publication bias, we would have a lot more studies that say “we tested this, and here are our results, which didn’t help answer our question at all”—which would be bad for the publication, but good for science, because data is data.
To put it in non-numerical terms: this is the same misrepresentation as the technically true phrase “when I misplace something, it’s always in the last place I look for it”—obviously it is, because that’s when you stop looking.
There’s not a good way to check for this, but be sure to check out sample sizes and see that they’re reassuringly large.
Reporting/Detection/Survivorship Bias
There’s a famous example of the rise in “popularity” of left-handedness. Whilst Americans born in ~1910 had a bit under a 3.5% chance of being left handed, those born in ~1950 had a bit under a 12% change.
Why did left-handedness become so much more prevalent all of a sudden, and then plateau at 12%?
Simple, that’s when schools stopped forcing left-handed children to use their right hands instead.
In a similar fashion, countries have generally found that homosexuality became a lot more common once decriminalized. Of course the real incidence almost certainly did not change—it just became more visible to research.
So, these biases are caused when the method of data collection and/or measurement leads to a systematic error in results.
How to check for this: you’ll need to think this through logically, on a case by case basis. Is there a reason that we might not be seeing or hearing from a certain demographic?
And perhaps most common of all…
Confounding Bias
This is the bias that relates to the well-known idea “correlation ≠ causation”.
Everyone has heard the funny examples, such as “ice cream sales cause shark attacks” (in reality, both are more likely to happen in similar places and times; when many people are at the beach, for instance).
How can any research paper possibly screw this one up?
Often they don’t and it’s a case of Spin Bias (see above), but examples that are not so obviously wrong “by common sense” often fly under the radar:
“Horse-riding found to be the sport that most extends longevity”
Should we all take up horse-riding to increase our lifespans? Probably not; the reality is that people who can afford horses can probably afford better than average healthcare, and lead easier, less stressful lives overall. The fact that people with horses typically have wealthier lifestyles than those without, is the confounding variable here.
See This And Many More Educational Cartoons on XKCD.com!
In short, when you look at the scientific research papers cited in the articles you read (you do look at the studies, yes?), watch out for these biases that found their way into the research, and you’ll be able to draw your own conclusions, with well-informed confidence, about what the study actually tells us.
Science shouldn’t be gatekept, and definitely shouldn’t be abused, so the more people who know about these things, the better!
So…would one of your friends benefit from this knowledge? Forward it to them!
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7 Steps to Get Off Sugar and Carbohydrates – by Susan Neal
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We will not keep the steps a mystery; abbreviated, they are:
- decide to really do this thing
- get knowledge and support
- clean out that pantry/fridge/etc and put those things behind you
- buy in healthy foods while starving your candida
- plan for an official start date, so that everything is ready
- change the way you eat (prep methods, timings, etc)
- keep on finding small ways to improve, without turning back
Particularly important amongst those are starving the candida (the fungus in your gut that is responsible for a lot of carb cravings, especially sugar and alcohol—which latter can be broken down easily into sugar), and changing the “how” of eating as well as the “what”; those are both things that are often overlooked in a lot of guides, but this one delivers well.
Walking the reader by the hand through things like that is probably the book’s greatest strength.
In the category of subjective criticism, the author does go off-piste a little at the end, to take a moment while she has our attention to talk about other things.
For example, you may not need “Appendix 7: How to Become A Christian and Disciple of Jesus Christ”.
Of course if that calls to you, then by all means, follow your heart, but it certainly isn’t a necessary step of quitting sugar. Nevertheless, the diversion doesn’t detract from the good dietary change advice that she has just spent a book delivering.
Bottom line: there’s no deep science here, but there’s a lot of very good, very practical advice, that’s consistent with good science.
Click here to check out 7 Steps to Get Off Sugar, and watch your health improve!
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Buffed-Up Buffalo Cauliflower
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This is a tasty snack that also more protein than you’d think, because of the garbanzo bean flour. It also has plenty of health-giving spices, as well as blood-sugar-balancing vinegar, no added sugar, and very little salt.
You will need
- 1 medium head of cauliflower, cut into florets
- ½ cup garbanzo bean flour
- ½ cup water
- ⅓ cup hot sauce (we recommend a low-sugar kind; Nando’s hot sauce is good for this if available where you are, as it has no added sugar and its main ingredient by volume is vinegar, which is good for balancing blood sugars)
- 2 tbsp extra virgin olive oil, plus more for the pan
- 2 tsp garlic powder
- 2 tsp nutritional yeast
- 2 tsp black pepper, freshly ground
- 1 tsp smoked paprika
- ½ tsp MSG, or 1 tsp low sodium salt
For the ranch sauce:
- ½ cup raw sunflower seeds
- ⅓ cup water
- ⅓ cup milk (plant milk being healthiest if you choose one that’s unsweetened)
- 2 tbsp apple cider vinegar
- 2 tbsp extra virgin olive oil
- 1 tsp onion powder
- 1 tsp dried thyme
- 1 tsp dried oregano
- 1 tsp dried dill
- ½ tsp MSG, or 1 tsp low sodium salt
Method
(we suggest you read everything at least once before doing anything)
1) Preheat the oven to 400℉/200℃.
2) Blend the ranch sauce ingredients until smooth, and set aside.
3) Mix the buffalo cauliflower ingredients except for the cauliflower, in a big bowl.
4) Add the cauliflower to the big bowl, mixing well to coat evenly.
5) Bake the buffalo cauliflower florets on a baking tray lined with baking paper, for about 25 minutes, turning gently if it seems they are at risk of cooking unevenly.
6) Serve hot, with the sunflower ranch on the side!
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
- An Apple (Cider Vinegar) A Day…
- 10 Ways To Balance Blood Sugars
- Our Top 5 Spices: How Much Is Enough For Benefits?
Take care!
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The Problem With Sweeteners
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The WHO’s new view on sugar-free sweeteners
The WHO has released a report offering guidance regards the use of sugar-free sweeteners as part of a weight-loss effort.
In a nutshell, the guidance is: don’t
- Here’s the report itself: Use of non-sugar sweeteners: WHO guideline
- Here’s the WHO’s own press release about it: WHO advises not to use non-sugar sweeteners for weight control in newly released guideline
- And it was based on this huge systematic review: Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis
They make for interesting reading, so if you don’t have time now, you might want to just quickly open and bookmark them for later!
Some salient bits and pieces:
Besides that some sweeteners can cause gastro-intestinal problems, a big problem is desensitization:
Because many sugar substitutes are many times (in some cases, hundreds of times) sweeter than sugar, this leads to other sweet foods tasting more bland, causing people to crave sweeter and sweeter foods for the same satisfaction level.
You can imagine how that’s not a spiral that’s good for the health!
The WHO recommendation applies to artificial and naturally-occurring non-sugar sweeteners, including:
- Acesulfame K
- Advantame
- Aspartame
- Cyclamates
- Neotame
- Saccharin
- Stevia
Sucralose and erythritol, by the way, technically are sugars, just not “that kind of sugar” so they didn’t make the list of non-sugar sweeteners.
That said, a recent study did find that erythritol was linked to a higher risk of heart attack, stroke, and early death, so it may not be an amazing sweetener either:
Read: The artificial sweetener erythritol and cardiovascular event risk
Want to know a good way of staying healthy in the context of sweeteners?
Just get used to using less. Your taste buds will adapt, and you’ll get just as much pleasure as before, from progressively less sweetening agent.
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Does intermittent fasting increase or decrease our risk of cancer?
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Research over the years has suggested intermittent fasting has the potential to improve our health and reduce the likelihood of developing cancer.
So what should we make of a new study in mice suggesting fasting increases the risk of cancer?
What is intermittent fasting?
Intermittent fasting means switching between times of eating and not eating. Unlike traditional diets that focus on what to eat, this approach focuses on when to eat.
There are lots of commonly used intermittent fasting schedules. The 16/8 plan means you only eat within an eight-hour window, then fast for the remaining 16 hours. Another popular option is the 5:2 diet, where you eat normally for five days then restrict calories for two days.
In Australia, poor diet contributes to 7% of all cases of disease, including coronary heart disease, stroke, type 2 diabetes, and cancers of the bowel and lung. Globally, poor diet is linked to 22% of deaths in adults over the age of 25.
Intermittent fasting has gained a lot of attention in recent years for its potential health benefits. Fasting influences metabolism, which is how your body processes food and energy. It can affect how the body absorbs nutrients from food and burns energy from sugar and fat.
What did the new study find?
The new study, published in Nature, found when mice ate again after fasting, their gut stem cells, which help repair the intestine, became more active. The stem cells were better at regenerating compared with those of mice who were either totally fasting or eating normally.
This suggests the body might be better at healing itself when eating after fasting.
However, this could also have a downside. If there are genetic mutations present, the burst of stem cell-driven regeneration after eating again might make it easier for cancer to develop.
Polyamines – small molecules important for cell growth – drive this regeneration after refeeding. These polyamines can be produced by the body, influenced by diet, or come from gut bacteria.
The findings suggest that while fasting and refeeding can improve stem cell function and regeneration, there might be a tradeoff with an increased risk of cancer, especially if fasting and refeeding cycles are repeated over time.
While this has been shown in mice, the link between intermittent fasting and cancer risk in humans is more complicated and not yet fully understood.
What has other research found?
Studies in animals have found intermittent fasting can help with weight loss, improve blood pressure and blood sugar levels, and subsequently reduce the risks of diabetes and heart disease.
Research in humans suggests intermittent fasting can reduce body weight, improve metabolic health, reduce inflammation, and enhance cellular repair processes, which remove damaged cells that could potentially turn cancerous.
However, other studies warn that the benefits of intermittent fasting are the same as what can be achieved through calorie restriction, and that there isn’t enough evidence to confirm it reduces cancer risk in humans.
What about in people with cancer?
In studies of people who have cancer, fasting has been reported to protect against the side effects of chemotherapy and improve the effectiveness of cancer treatments, while decreasing damage to healthy cells.
Prolonged fasting in some patients who have cancer has been shown to be safe and may potentially be able to decrease tumour growth.
On the other hand, some experts advise caution. Studies in mice show intermittent fasting could weaken the immune system and make the body less able to fight infection, potentially leading to worse health outcomes in people who are unwell. However, there is currently no evidence that fasting increases the risk of bacterial infections in humans.
So is it OK to try intermittent fasting?
The current view on intermittent fasting is that it can be beneficial, but experts agree more research is needed. Short-term benefits such as weight loss and better overall health are well supported. But we don’t fully understand the long-term effects, especially when it comes to cancer risk and other immune-related issues.
Since there are many different methods of intermittent fasting and people react to them differently, it’s hard to give advice that works for everyone. And because most people who participated in the studies were overweight, or had diabetes or other health problems, we don’t know how the results apply to the broader population.
For healthy people, intermittent fasting is generally considered safe. But it’s not suitable for everyone, particularly those with certain medical conditions, pregnant or breastfeeding women, and people with a history of eating disorders. So consult your health-care provider before starting any fasting program.
Amali Cooray, PhD Candidate in Genetic Engineering and Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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The Obesity Code – by Dr. Jason Fung
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Firstly, if you have already read Dr. Fung’s other book, The Diabetes Code, which we reviewed a little while ago, you can probably skip this one. It has mostly the same information, presented with a different focus.
While The Diabetes Code assumes you are diabetic, or prediabetic, or concerned about avoiding/reversing those conditions, The Obesity Code assumes you are obese, or heading in that direction, or otherwise are concerned about avoiding/reversing obesity.
What it’s not, though, is a weight loss book. Will it help if you want to lose weight? Yes, absolutely. But there is no talk here of weight loss goals, nor any motivational coaching, nor week-by-week plans, etc.
Instead, it’s more an informative textbook. With exactly the sort of philosophy we like here at 10almonds: putting information into people’s hands, so everyone can make the best decisions for themselves, rather than blindly following someone else’s program.
Dr. Fung explains why various dieting approaches don’t work, and how we can work around such things as our genetics, as well as most external factors except for poverty. He also talks us through how to change our body’s insulin response, and get our body working more like a lean machine and less like a larder for hard times.
Bottom line: this is a no-frills explanation of why your body does what it does when it comes to fat storage, and how to make it behave differently about that.
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