For the past year, BioLongevity Labs has been working on a top-secret project.

An extraordinarily ambitious feat involving the best minds in biochemistry and therapeutic peptides.

We attempted to synthesize and manufacture two compounds that we believe will be the de novo standard for all future longevity optimization treatments.

When combined together, they will enhance metabolic rate and cause (potentially) permanent skeletal muscle gain.

And naturally extend both the years you live and the number of quality years you can live, of course.

Those of you who have been tuning in to my weekly live shows, FOH LIVE to to the public and my weekly AMA’s in the private Fully Optimized Health membership group, you already know what they are.

If you don’t, prepare to be amazed.

I AM talking about Klotho and Recombinant Follistatin, a foundational anti-aging protein and a popular underground hypertrophy-inducing protein that was once a dead end but has been re-engineered from the ground up.

They are not only exceptional when used alone, but the synergy when both are stacked together will lead to effects beyond your imagination.

Today’s article focuses on Klotho, one of the strongest anti-aging molecules known to man and the next big thing coming to the longevity space.

Part 2 will then focus on Recombinant Follistatin.

Let’s dive in!

Special credit goes to BioLongevity Labs’ Chief Science Officer Bryan Moskow and our unnnamed in-house chemist for putting their heads together to create both products and supply us with all the technical information required to write this article.

What is Klotho?

 

What you’re about to se is the next big thing coming to the longevity space, and arguably one of the strongest anti-aging molecules known to man.

The name “Klotho” is derived from Greek mythology:

“Klotho was one of the three Fates in Greek mythology. Klotho and her two sisters, Lachesis and Atropos, controlled the thread of life of each human being.

Klotho was responsible for spinning the thread of life. She also possessed the power to choose who was saved or put to death. 

…Lachesis, the second of the three Fates, was responsible for measuring the length of the thread and deciding how much time of life was allowed for each human being.

The third Fate Atropos was the oldest of the three sisters. She was the one who chose the mechanism of death and how the life of a mortal ended by cutting the thread of life with her shears.

It was said that the three Fates appear within three days of someone’s birth to decide their fate. Klotho’s place in Greek mythology alongside her sisters was significant.”

The name was therefore fitting for a gene that was discovered in 1997 by Japanese researchers, in which a mutational defect within the gene’s expression led to accelerated aging in mice:

“Mutations of klotho cause rapid aging in mice homozygous for the mutant.

While these mice develop normally through three to four weeks of age, they have a greatly shortened lifespan and eventually display a series of diseases characteristic of human aging: arteriosclerosis, osteoporosis, emphysema, and skin atrophy. The animals also are infertile.

Introduction of a normal klotho gene into these mice results in mice with normal aging.”

The researchers went on to say that the mice with the mutation in the Klotho gene should be regarded as a model of premature aging syndromes in humans because their displayed phenotypes matched much of the existing pathophysiological criteria that defines human aging.

More importantly, there was no lab mouse in existence at the time that would develop the syndrome observed in the mice with the Klotho gene defect independent of how long they would live.

And the reverse is also true: When the Klotho gene in mice is overexpressed, you see an extension of lifespan and a slowing down of the aging process.

But with this background story established, let’s talk more about what Klotho actually is…

Humans have a gene called “KL” that encodes three variations of the Klotho protein, which are known as “subfamilies”: α-klotho, β-klotho, and γ-klotho.

The former is what we are particularly interested in, which itself ALSO has 3 types: an α-Klotho that is a full-length transmembrane protein (i.e. membrane-bound), a truncated soluble α-Klotho (i.e. hormonal in nature), or an α-Klotho that is secreted.

The second one is what lies in our interest, so let’s focus on that one: Soluble α-Klotho, the one circulating in blood with an estimated 7.5 hour half-life.

In terms of its origin within the body, α-Klotho is primarily expressed within the kidney, specifically the distal convoluted tubule.

However, you’ll find it in several tissues and cell types that include: The sex organs (ovary, placenta, testis), the choroid plexus within the brain, parathyroid gland, and the renal proximal tubule within the kidney.

Another important thing to know about α-Klotho is it acts as a co-receptor for FGF23 (Fibroblast Growth Factor 23):

“Endocrine FGF23 regulates phosphate and vitamin D homeostasis by reducing the cell surface expression of sodium phosphate co-transporters and by repressing transcription of rate-limiting enzymes for vitamin D biosynthesis in the kidney.

FGF23 exerts its metabolic functions by binding and activating FGFR tyrosine kinases in an α-klotho co-receptor dependent fashion”

(NOTE: A co-receptor simply defines a receptor on a cell’s surface that binds to both a primary receptor and a signalling molecule and results in a cascade of biological processes)

I want to make one more distinction here between membrane-bound α-Klotho and soluble α-Klotho:

“Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis by activating complexes of FGF receptors and transmembrane klotho co-receptors. A soluble form of klotho also acts as a ‘portable’ FGF23 co-receptor in tissues that do not express klotho”

(Source)

This then leads to Klotho regulating the  metabolism of vitamin D, calcium, and phosphate (we’ll see why this is important later).

The next question for us to ask is what exactly happens to α-Klotho levels in the body as we get older.

As with most beneficial compounds endogenously produced in the body, its production goes down with time  in healthy adults:

• 18-35 years old: 932.6 pg/mL (~0.9ng/mL)
• 35-55 years old: 796.7 pg/mL (~0.8ng/mL)
• 55-85 years old: 612.1 pg/mL (~0.6ng/mL)

NOTE: pg = picogram. 1000 picograms = 1 nanogram (ng), 1000ng = 1 microgram (μg), 1000 μg = 1 milligram (mg). Just to show you how RIDICULOUSLY small this number is.

This trend occurs regardless of sex, and is entirely attributed to “physiological decline derived from the aging process”.

If we do some rough math, this adds up to a range of 2.5μg to 15μg in the body.

Older people will have 2.5μg of circulating soluble α-Klotho or slightly higher and be at the lower end, whereas younger people who are gifted will have readings that go up to a maximum of 15μg.

So if one were to theoretically provide an older individual with exogenous α-Klotho, we would be doing so to get them in that upper range.

Our final question for now is how dangerous it is to be α-Klotho deficient as you get older.

The answer is quite clear:

• In older adults, “a strong association between lower Klotho levels and increased disability in activities of daily living, increased risk of frailty, lower performance in the short physical performance battery (SPPB), lower grip strength, and lower knee strength” (Source)
• “Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with [chronic kidney disease]” (Source)
• In middle-aged adults, there is an inverse relationship between Klotho levels and low muscle mass (i.e. higher Klotho levels are assocaited with a lower risk of muscle loss) (Source)

As one article so succinctly puts it:

“An insufficiency of the klotho protein has been associated with kidney problems, cardiovascular disease, cancer, neurological issues like cognitive deficits and Alzheimer’s disease, as well as lung, bone, and metabolic problems, like osteoporosis and diabetes.

That does not make klotho the cause of these varied diseases, though; its low levels have simply been found at those metaphorical crime scenes, like those of so many other molecules.”

(Source)

Of course, while exercise itself can increase Klotho levels, in our neck of the woods we want something much more.

And we firmly believe we’ve stumbled upon something that works better than anything out there.

How is Klotho From BioLongevity Labs Different From Normal Klotho?

 

At BioLongevity Labs, we have created something called “α-Klotho MAB”

For technical purposes, other synonyms we use in-house include “α-Klotho-albumin binding construct” or “Modified Klotho with glycine-serine linker”

There’s a lot to digest here, so let’s explain every part one at a time…

This is a patented and modified version of the recombinant Klotho protein that takes α-Klotho (1012 amino acids) and combines it with a proprietary 29-amino acid long albumin binding construct (GGSGGSGGSGGRLIEDICLPRWGCLWEDD).

Here’s what you get when all of this happens:

• Molecular weight = ~133-135 kDa
• Albumin binding affinity (Kd) = <20 nM
• Native FGF23 binding activity = 15-30 nM (optimized: 16.2 nM, relative to the binding affinity between soluble α-Klotho and human FGF23 being 13-18nM as measured by its dissociation constant)
• Half-life = up to 19 days for a smooth pharmacokinetic curve (compared to the 7.5 hours for native α-Klotho)

(Yes, we have full analytical documentation and extensive independent 3rd-party testing that supports all of the numbers above)

The “MAB” stands for “modified albumin binder”, a small but important distinction as this acronym is often shorthand for “monoclonal antibody” in many other contexts.

And the patented albumin binder is our secret sauce, one that has been developed, perfected and patented over many years by our in-house chemist (who will remain unnamed for now).

This albumin binder is what allows us to create a version of Klotho with improved efficacy, better absorption, prevention of metabolic breakdown (i.e. better stability), and an extended half-life to result in a controlled release instead of a bolus dose.

(NOTE: This is the same albumin binder that will be end up being used in Recombinant Follistatin, so you’ll be reading about it again in our next article). 

Benefits

I AM convinced our proprietary formulation of the human Klotho gene will be something any man or woman 35 years of age or older focused on living and stronger will want to use.

Clearly, having low levels of Klotho in your body will negatively impact multiple biological systems due to its strong link with accelerated aging.

So what happens when we have high levels of Klotho instead?

You’re about to find out while discovering why Klotho will be the next “IT” thing in the longevity space.

Mitochondrial Biogenesis

Those of you who have read my past writings about the mitochondria are familiar with the term “mitochondrial biogenesis”, which defines the process by which new mitochondria are generated while the DNA within mitochondria (mtDNA) are maintained.

In other words, you increase both the mass and density of mitochondria within the cell.

Klotho comes in by up-regulating mitochondrial biogenesis when its circulating levels are high.

We know this happens because its expression or enhancement thereof is what consistently leads to improvements in mitochondrial dysfunction.

This happens through a wide variety of biological cascades, of which the technical names are not particularly important for now.

What does matter is WHY this benefit is listed first.

There are several disease states that stem directly from and/or are strongly linked to mitochondrial dysfunction: Cardiovascular disease, kidney disease, and metabolic disease overall… all symptomatic diseases of aging.

When you fix mitochondrial function, you increase the body’s ability to perform.

You boost the efficiency of your cells and you therefore boost everything we associate with a healthy and vital organism.

This leads to the effects of Klotho being felt across all organ systems, especially the ones with high-energy requirements such as lungs, heart, brain, kidney, and muscle.

In practice, you are giving each organ more mitochondria to help them meet their energy demands.

And on the flipside, when you lose mitochondrial density, each of these systems will be negatively affected dramatically and equally (i.e. the heart will be as affected as the kidney).

And this is unlike the mitochondrial peptides SS-31 and MOTS-C, which can influence mitochodrial health in the long-run but nowhere near the degree Klotho can as they cannot stimulate mitochondrial biogenesis.

(Not to mention MOTS-C is also banned by WADA)

Thanks to soluble α-Klotho circulating through the body, its effects are systemic and not specific to the kidney.

Hopefully it’s starting to become clear how Klotho is directly related to the underlying health of every single major organ system in the body!

Better Cognition

One interesting thing about soluble α-Klotho is that it cannot penetrate the blood-brain barrier (BBB), but yet it somehow has a direct effect on cognition.

How exactly we don’t know, but we do know that Klotho over-expression leads to higher levels of low-density lipoprotein receptor-related protein 1 (LRP1), which correlates to excretion of and elimination of proteins associated with Alzheimer’s Disease:

“Endothelial LRP1 plays a vital role in removing [amyloid-β plaques], and its expression decreases with age.

This decrease is more pronounced in Alzheimer’s  patients and animal models, where BBB LRP1 levels are almost undetectable.

The downregulation of LRP1 is strongly correlated with impairment of the BBB and cognitive decline.

Proper regulation of LRP1 levels in endothelial cells is crucial for preventing the progression of Alzheimer’s Disease”

We also have other pieces of evidence, such as this patent whereby Klotho injections done intraperitoneally directly improved cognition in aged animal models and interfered with neurodegeneration.

And this Nature study that made headlines in 2023, involving the same person (Dena Dubal) who authored the patent I just mentioned.

She took older-aged monkeys and measured their cognitive capabilities via a spatial memory test before and after a Klotho injection, finding their memory was correct 45% of the time before the injection and 60% of the time after the injection.

What was really cool about this study is that low doses were effective but not high doses, and the improvements in cognition and synaptic plasticity lasted for two weeks following the single injection!

Lastly, it’s not surprising to see studies in humans where low soluble α-Klotho levels are consistently associated with worsening cognitive outcomes.

Restored Kidney Function

If you recall my introduction of Klotho, you’ll remember soluble α-Klotho and FGF23 are co-factors in binding to the FGF receptor, which leads to the excretion of phosphate and then allows for the balance of other micronutrients and minerals such as calcium and sodium.

As you can imagine, low Klotho levels are bad news bears for anybody concerned about kidney health:

• Independently associated with arterial stiffness in patients with chronic kidney disease (Source)
• Downregulated in patients with chronic kidney disease, with its levels implicated in the progression of the disease (i.e. as the disease gets more advanced, Klotho levels go down) (Source)
• Low levels are inversely correlated with estimated glomerular filtration rate (eGFR) (Source)

Fortunately, it is indeed possible to explore Klotho as a therapeutic treatment for kidney damage.

Some preclinical studies have shown the use of exogenous Klotho to upregulate and/or maintain its levels in the body can attenuate injury to the kidney, slow down the progression of chronic kidney disease, and improve overall kidney function.

But I want to turn our attention to a condition that kidney disease sufferers are often afflicted with, and it’s called vascular calcification (i.e. buildup and accumulatio of calcium deposits in the arteries and veins):

“Vascular calcification (VC) appears early in the course of CKD (chronic kidney disease) but becomes much more prevalent as kidney function deteriorates, creating a strong risk of cardiovascular mortality and morbidity in patients with CKD and ESRD (end stage renal disease). 

VC can be classified based on the vascular site of abnormal mineral deposition, including intimal calcification, medial calcification, and valvular calcification, which are all highly prevalent in the CKD population”

Klotho comes in because — you guessed it — low levels can cause more VC to happen alongside higher circulating phosphate levels.

One of the test you can do to measure how much calcium is accumulating in your arteries is called a coronary artery calcium test (CAC), where a higher number indicates a higher risk of a heart attack.

But with Klotho levels elevated, you can reduce VC and stop your arteries from hardening any further and make them more flexible, while the excess mineral load can be redirected into supporting bone health.

Improved Blood Flow

On the topic of blood, Klotho is also known to enhance the production of nitic oxide and act as a protective factor of the endothelial system against dysfunction.

What does this mean for you?

As you vasodilate the blood vessels and release nitric oxide through the endothelial system (i.e. the interior layer lining your blood vessels), you can further push oxygen and nutrients into the far reaches of your body that require them.

There’s probably some anti-inflammatory mechanisms of Klotho that contribute to this phenomenon as well.

In addition, you can also remove the toxins generated by your organs every time they function with more efficiency, which allows the whole organism to function more effiiciently.

Likewise, if we look at the downside of low Klotho levels, we see they can serve as not only a prognostic for essential hypertension, but probably contribute to its pathogenesis as well.

Fixed Lung Function

Related to the topic of vasodilation we just discussed, it is clear Klotho also impacts how your lungs operate:

“Acquired circulating α-Klotho deficiency, for example, in renal disease, predisposes to secondary lung injury and exacerbates coexisting hemodynamic, metabolic, and pro‐inflammatory factors contributing to lung dysfunction.

In rats with ischemia‐reperfusion kidney injury and severely reduced plasma α-Klotho level, acute lung injury develops quickly; repletion of circulating αKlotho alleviates pulmonary complications independent of the severity of kidney injury.

By inference, age‐related decline in renal α-Klotho synthesis may also heighten susceptibility to lung injury in the elderly.”

Despite α -Klotho not being normally expressed in lung cells, it is nevertheless critical for overall lung health:

“As renal α-Klotho production declines with age or disease, an imbalance between pulmonary toxin delivery and cytoprotective capacity is created that predisposes to lung degeneration and dysfunction.

Local or systemic diseases, for example, diabetes mellitus and cardiovascular disorders, that cause renal impairment further reduce αKlotho synthesis and accelerate widespread age‐exacerbated organ degeneration in the lung.

Primary acute or chronic lung disease may secondarily impair renal function and reduce circulating αKlotho level, thereby aggravating lung degeneration in a vicious cycle.

Thus, circulating αKlotho delivery to the lung is a plausible mechanism of pulmonary‐renal crosstalk and explains an important aspect of reciprocal interdependence between these two organs”

One of the first signs of aging is having not only kidney dysfunction, but pulmonary dysfunction as well.

As you decrease Klotho levels, lung function also decreases dramatically.

And it’s in the lungs where we exchange oxygen with the exterior environment; through vasodilation of the capillaries, we allow proper oxygenation of the blood and for the blood to be carried away with all this oxygen.

That’s why studies show higher Klotho levels are positively correlated with better pulmonary function.

Klotho, despite its small size, modulates almost EVERY organ’s function in the body!

Better Sex & Physical Endurance

I’ll put these two benefits together as I don’t have a whole lot to say about them.

On the matter of physical endurance, it makes sense augmenting Klotho leads to augmenting of mitochondrial biogenesis, which then augments the body’s endurance capabilities.

While we don’t have the human studies to verify this, in mice we consistently see that Klotho-deficient animals have a markedly reduced ability to run on the treadmill compared to mice without the deficiency.

There’s also the boost in basal metabolism… again, human data is absent to say exactly what that means in measured calories burned in a real-world setting, but mice studies (here and here) seen to point toward increased energy expenditure.

On the subject of sex, a few weeks of Klotho use has led to a huge boost in energy and pheromone response for me and my wife.

My chemistry and excitement are on a completely different level now… we’re both much more attracted to each other than usual, almost like you’re 18 again for the first time.

Higher sex drive and stronger erections are two things I will NEVER say no to!

Some evidence suggests a positive correlation between Klotho levels and testosterone levels, along with soluble α-Klotho being strongly associated with sexual desire and function in sedentary middle-aged adults.

Not definitive proof by any stretch of the imagination, but just an on-the-field observation.

Dosing Klotho For Best Results

Pay very close attention because the instructions I AM giving you specifically pertain to BioLongevity Labs’ “α-Klotho MAB” and nothing else.

So if you attempt to use what you’re going to see with another formulation of Klotho on the Internet… there’s nothing I can do for you.

The proper dose of α-Klotho MAB is a subcutaneous or IM injection of 10mcg (10 micrograms) done once every 2 weeks. 

That is literally it — no need to cycle or do anything else

As a healthy individual in their 30-80s, effects will be subtle but noticeable within a week due to improved endothelial functioning ie. noticeable and improved sensitivity to feel, taste, smell etc.

Perhaps 2-4 weeks if you are looking for improvements in endurance.

For a more diseased individual, especially one suffering from renal issues, expect symptom improvements within 4-6 weeks (along with high-performing athletes looking for performance bumps as the effects may be more subtle)

If you are an older individual, you’ll feel the effects faster than a younger individual as they are already in the upper range of optimal Klotho levels.

This dose allows you to optimize Klotho levels in a range that keeps it within the parameters of good health (the same range of 2.5-15 mcg mentioned at the start of the article).

And it’s all possible thanks to a couple of things.

First, there is the albumin binder mentioned earlier which extends the half life and improves systemic efficacy allowing for the doses to be spread out every two weeks.

Second, there is the fact exogenous Klotho use actually has been shown in several studies (here, here and here) to not only retain endogenous Klotho expression, but also restore down regulated Klotho expression, up-regulate it in some cases (here and here) and could raise serum Klotho levels at the same time.

All you’re really doing is replacing your body’s declining values of Klotho without any negative feedback loop.

This is much different than what you see with hormonal treatments such as therapeutic testosterone whereby the hypogonadal axis is disturbed once exogenous testosterone replaces the body’s own supply.

The only thing I should give you a heads-up on is if you stop using Klotho, your levels will decline back to where they were before you started.

But frankly, you should view Klotho use as foundationally as you view testosterone.

We don’t know for sure if Klotho will increase lifespan in humans, but it sure as hell will improve your health dramatically.

If you are an aging man or woman desiring to live longer and stronger, supplementation with Klotho should be priority #1.

Side Effects

If there was any one major side effect I would warn potential Klotho users about, it would be DO NOT DOSE MORE THAN WHAT IS RECOMMENDED!

The range of Klotho we were discussing earlier, is EXACTLY where you want to be if you want to improve health and athletic performance as you age.

There’s a reason why we set things up the way we did with the tiny dose and the extended half life.

Understanding the human body only makes about 4mcg of Klotho daily, our product is designed to provide a slow yet steady release instead of a massive bolus dose.

When one goes above our recommended doses and exits the upper end of the healthy range of Klotho levels, bad things start to happen.

Especially since we now know exogenous use of Klotho also activates the genes in your body to potentially increase its endogenous production of it.

For starters, nitric oxide is a great vasodilator but it is also a free radical… so too much of it can lead to oxidative stress and this will end up being counterproductive.

That can then lead to very deleterious outcomes including kidney damage and vascular damage due to endothelial malfunction.

Next, supraphysiological levels of Klotho can do the opposite of the health benefits described earlier: Promotion of vascular calcification, excreting massive amounts of phosphates (hypophosphatemia) and potassium (hypokalemia).

You see this all the time in bodybuilders who take dangerous amounts of diuretics, and they often end up suffering from cardiac irregularities (arrythmia) along with kidney failure because you’re overstressing it with the tremendous amount of energy it would take to excrete all the excess metabolites and nutrients.

(For this reason, it probably wouldn’t hurt to supplement with electrolytes while using Klotho to avoid putting yourself in a depleted state)

Even taking milligrams, or way too many micrograms if you get the math wrong, could be too much for your system to handle!

Don’t come complaining to me or BioLongevity Labs if your recklessness puts your health in a compromised state.

Aside from that major warning, I’ll just mention two more minor side effects in brief:

• You’ll find yourself more energized than usual, so attempt to relax an hour before bed and prepare for a good 7-8 hours of sleep. Use something like melatonin to help yourself fall asleep if you have to
• Your body may feel slightly warm (i.e. a burning sensation) due to the mitochondrial biogenesis happening. Your basal rate metabolism may go up to the point where putting on muscle is a bit harder due to the energy expenditure, so you’d have to increase caloric intake to compensate (but for that same reason, the side effect is EXCELLENT for fat loss)

Where To Buy Klotho

Due to the ongoing chaos within the world of Trump Tariffs, α-Klotho MAB is currently wait list only at BioLongevity Labs. 

After tomorrow’s article on Recombinant Follistatin (FLGR242) launches, both of these revolutionary products will be available for presale within 36 hours.

As soon as they arrive in our warehouse, you’ll be the first one to get the notification if you’re subscribed to my email list and on the Klotho and Follistatin wait lists

What I can promise is.. you will be able to buy either one in isolation or both of them at once, and there will be a massive incentive for anybody who buys a year’s supply of both products.

Klotho is the one peptide you’ll want to use forever and ever as an aging human being.

And when you feel its incredibly amazing biological effects  like Monica and I both do every single day, you might start wondering how you can invest into BioLongevity Labs? 😍

But let me be the first to warn you about your future purchase.

When it comes to ANY peptide, quality makes all the difference.

Just as you wouldn’t put low-grade fuel in a precision engine, you sure wouldn’t put anything less than the purest peptides in your body.

That’s why source quality and manufacturing standards matter.

I’ve personally vetted dozens of peptide suppliers, and I can tell you this without hesitation:

BioLongevity Labs sets the benchmark for authentic USA manufactured research peptides and small molecules along with our brand new USA manufactured Khavinson bioregulators.

Each product is made with a ruthless focus on stringent third-party testing and top-notch customer service.

BLL consistently delivers the highest quality products, trusted by researchers for both personal and clinical use.

Whether you’re looking to elevate your performance or integrate these products into research applications, BioLongevity Labs is a reliable source you can count on.

👉 Click here to place your online order at BioLongevity Labs👈

Use code JayC to get 15% off your order!

I also invite you to join me and other like-minded biohackers in The Fully Optimized Health Private Membership Group.

This is where we dive deep into using peptides to optimize health, especially for those in their 30s and beyond. We’re also talking about cutting-edge biohacking and the latest and greatest in elite health optimization strategies.