Is it reliable? Responsive to CR?
3 Likes
[they use the painless tasso, i still dont know if this is evaluated to be legit by 3rd parties
===
But even when we focus on klotho and the role it plays in ageing, we rub against a common problem in biomedical research: what weâre using to look for klotho is not all that reliable. Antibodies are commonly used to detect a protein in the lab. The antibody is supposed to recognize a protein of interest (and only that protein). Once it is bound to it, it will be bound to by a second antibody that carries something visible or detectable, like a colour pigment or a fluorescent molecule. The issue is that many commercially available antibodies meant to be specific for one protein are revealed not to be, and tests done using an antibody from company A often do not match the same tests done using a similar antibody from company B, and antibodies sold for klotho detection have not escaped from this problem. Therefore, some of the knowledge weâve acquired about where klotho is in the body and what happens to its levels in this or that condition may not be correct. More rigour is needed to vet the very tools used to study klotho.
That hurdle hasnât stopped scientists from speculating about and, in some cases, testing actual therapies that involve increasing the levels of klotho in the body, often in laboratory animals. Here too, however, we face challenges. Simply ingesting the protein wouldnât work, as our digestive enzymes would chop it up into its building blocks, to be used to assemble different proteins in our body. Injecting people with the protein would be of no value in trying to reach the brain, for example, because klotho is so big, it is not thought to be able to move through the blood-brain barrier, a sort of anatomical border control that limits which molecules and microorganisms can enter the brain and potentially harm it. Scientists are thus experimenting with gene therapy and with small molecules that can increase the natural production of klotho protein in the body.
The issue is that many commercially available antibodies meant to be specific for one protein are revealed not to be, and tests done using an antibody from company A often do not match the same tests done using a similar antibody from company B, and antibodies sold for klotho detection have not escaped from this problem. Therefore, some of the knowledge weâve acquired about where klotho is in the body and what happens to its levels in this or that condition may not be correct. More rigour is needed to vet the very tools used to study klotho.
That hurdle hasnât stopped scientists from speculating about and, in some cases, testing actual therapies that involve increasing the levels of klotho in the body, often in laboratory animals. Here too, however, we face challenges. Simply ingesting the protein wouldnât work, as our digestive enzymes would chop it up into its building blocks, to be used to assemble different proteins in our body. Injecting people with the protein would be of no value in trying to reach the brain, for example, because klotho is so big, it is not thought to be able to move through the blood-brain barrier, a sort of anatomical border control that limits which molecules and microorganisms can enter the brain and potentially harm it. Scientists are thus experimenting with gene therapy and with small molecules that can increase the natural production of klotho protein in the body.
3 Likes
I ordered the Klotho test from Longevitylabsolutions.com, but havenât taken the test yet.
I also ordered a Jinfiniti Aging SOS Advanced panel that includes alpha-Klotho and my results from the blood draw on Jun-17-2024 came back recently and my Klotho number was 0.7ng/ml (Jinfiniti supplies a reference range of 5 - 30 ng/ml for youthful & healthy Klotho levels and anything under 3ng/ml listed as very deficient). Since most published results for alpha-Klotho have normal ranges of 0.8 - 2.0 ng/ml, I emailed Jinfiniti to find out why their normal ranges are so much higher : The founder She responded with:
" We use a very different assay and reference ranges are established by our own studies that have more subjects and with a variety of health conditions. Your Klotho is very low relative to what we see in most individuals. Low Klotho levels are usually associated with some health conditions in most individuals with very low Klotho. In your case, it may be related to diabetes, hypertension and related kidney suboptimal function.".
This confirms what AlexKChen quoted about antibody (ELISA) based Klotho tests not being very repeatable, so each ELISA panel may produce results that need to be scaled differently to estimate absolute ng/mL values, and those scaling factors are often wrong. So each test labs needs to generate their own reference ranges to interpret the Klotho test result.
3 Likes
Have you received the longevitylabsolutions results yet? Iâd rather not spend over $1,000 on the Jinfiniti for just this metric!
1 Like
Thereâs a new longevity company for klotho gene therapy (Jim OâNeill is on it), idk delivery method or further details.
3 Likes
I will be doing mailing in my Longevitylabsolutions sample 8/26/24.
Longevity Labs took almost 4 weeks to process the klotho test (I paid $199, but the current price is $229) and my result was 1156 pg/mL, which is at the upper end of the reference range (750-1250) for the 19-39 age group. This is exactly the opposite of the results I got from Jinfiniti on Jun-17-2024, which had me well below their reference range for youthful Klotho levels.
Here are the full reference ranges along with my test result from Longevity Labs:
SOLUBLE KLOTHO 1156 pg/mL
<548.8 is associated with 52% increased risk for all-cause mortality
<660.9 is associated with 58% increased risk for cardiovascular mortality
18-39 years: 740 â 1250
40-59 years: 550 â 1000
60-79 years: 350 â 750
over 79 years: 200 - 600
4 Likes
Longevity Labs disappeared, what happened?
I cannot access longevitylabsolutions.com either, but the usual website down detectors claim the website is up and so the problem is likely some blacklisting by anti-virus software or a temporary issue over the busy Black Friday weekend.
Iâve talked with Jinifinity and they will do a stand alone Alpha Klotho level and will soon be offering more range of panels. I can order it as of today including all processing/shipping ~$300. Their panel that currently has this is $1200, but has a lot of other things on it.
1 Like
Longevitylabs has two klotho blood tests - one is way more expensive than the other. Is there any real difference in usefulness between the two?
sent my sample in today⊠now how do i get injectable klotho?
====
Short answer
Longevity NutriCareâs âSoluble Klotho Blood Testâ is run in a CLIA-accredited laboratory (CLIA # 45D2297805, Longevity Lab Solutions, Spring TX) (www.hipaaspace.com), so the lab is legally permitted to report human diagnostic results in the United States.
That is a necessary baseline for reliabilityâbut it is not sufficient. The real-world accuracy of any α-klotho measurement still depends on three things you should verify before you spend $235:
| What to ask for | Why it matters | Typical red flags |
|---|---|---|
|
Assay platform & kit. âą Which manufacturer (e.g., IBL-America ELISA, Finostics TRF-immunoassay, MSD electrochemiluminescence)? âą Is it FDA-cleared, RUO, or an in-house LDT? |
Commercial ELISAs for klotho differ by up to an order-of-magnitude, and some show poor correlation with eGFR or each other (PubMed, PMC) | âResearch-use-onlyâ kit with no validation summary; no mention of duplicate wells or calibrators. |
| Validation data. Ask for the labâs summary of limit of detection, linearity, recovery, and intra-/inter-assay coefficient of variation (CV). | Good clinical labs publish or furnish these numbers (CV †8 % intra-run; †10 % inter-run is typical). | âProprietaryâ or unavailable performance metrics. |
| Sample-handling protocol. âą Venous serum vs. finger-prick-dried blood spots. âą Use of EDTA tubes + protease inhibitors. âą Max shipping time and temperature. | Klotho is a 130 kDa protein that degrades with freezeâthaw and proteolysis; DBS has not been formally validated for this marker. | Home finger-stick kit with no cold-chain requirement or stabilizer. |
If Longevity NutriCare cannot document those points, your result may have more analytical noise than biological signal.
How does it stack up against other options?
| Option | Regulatory status | What you get | Practical notes |
|---|---|---|---|
| Longevity NutriCare | CLIA-accredited independent lab (www.hipaaspace.com) | Home collection kit â soluble α-klotho report | Small lab (â10 employees) (LinkedIn); kit details and assay manufacturer not disclosed on the website (longevitynutricare.com) |
| Academic reference labs (eg, ARUP, Mayo) | CLIA + CAP; large QA teams | Most do not yet list clinical α-klotho; tests are offered only under IRB protocols or as research assays | |
| Research kits you run yourself | RUO only | ELISA plate, standards | You still need duplicate wells, calibrators, and a plate readerâand results remain non-diagnostic |
Bottom line
Longevity NutriCare looks legitimate from a regulatory standpoint, but the α-klotho assay itself is still an emerging, high-variability biomarker.
Before ordering, insist on seeing the assay validation summary and make sure the sample-handling protocol has been stress-tested. If the lab can provide robust CVs, established reference ranges, and documentation that the home-collection method preserves klotho integrity, the test can be a useful data point. Otherwise, you may be paying for a number that is difficult to interpret or reproduce.
(If you need help formulating specific questions to send the labâor want alternative ways to monitor renal-klotho biology such as FGF-23, phosphate, and eGFR panelsâjust let me know.)
3 Likes
KLOTHO LEVEL (pg/mL): 1,164.6
thank god, itâs high for any age group. And I donât need to supplement (for now). But I have to figure out a more surgical intervention for my FOXO3âŠ
1 Like
1 Like
https://x.com/DrDominicNg/status/1956827607221035357
well I drink very heavy quantities (I never knew how to do it until early this year, which removed the need for me to do other stimulants) and itâs not low. I donât think the effect size is huge among people
But effects are nullified at high doses
1 Like
Looks like the negative effects of coffee intake (on Klotho levels) is much stronger in women and women typically have higher levels of Klotho than men in the absence of coffee intake. The authors speculate that this is due to coffee interfering in the beneficial effects of estrogen on Klotho levels and hence the effect is stronger in women.
1 Like
Im curious. Which stimulants were you on before?
Would you trust a paper from Wuhan? I wouldnât. Not for all the tea in China.
1 Like
Short answer: Probably not. At a serum αâklotho of ~1123 pg/mL you already sit in the high end of population distributions. In human datasets, cognitive and aging signals generally improve when moving people from low klotho into the middle/upperâmiddle range; above that, benefits plateauâand in at least one large cohort the highest levels were linked to higher, not lower, mortality risk. There are no human trials showing that pushing klotho higher from an alreadyâhigh baseline boosts cognition or slows aging. In animals, lowâdose klotho can sharpen memory in older brains, but effects are doseâsensitive and donât map cleanly to healthy humans. (PMC)
Where 1123 pg/mL sits
- In NHANES analyses (U.S. population, ages 60â79), the top quartile of serum klotho begins around ~960â983 pg/mL; median values in adults are near ~800 pg/mL depending on assay and cohort. Your 1123 pg/mL is firmly above the 75th percentile. (Assay differences matter, but these give the scale.) (PMC)
Does âmore klothoâ correlate with better human cognition?
- Crossâsectional cohorts: Moving from the lowest quartile up is associated with better test performance (e.g., Digit Symbol Substitution), but gains largely flatten beyond the midâhigh range; the bottomâquartile is the group that consistently looks worse. (PMC)
- Genetics (polymorphisms): Early reports that KLâVS heterozygotes perform better have not replicated in very large datasets; a UK Biobank analysis of >300k adults found no association between KL variants (including KLâVS) and cognitive level or change. (Brunel University Research Archive)
- Causality (Mendelian randomization): Instruments for higher circulating klotho do not show a causal reduction in Alzheimerâs disease risk; observational associations may reflect confounding. (Nature)
- Brain pathology vs blood levels: In biomarker studies, higher CSF klotho tracks with lower Alzheimerâtype pathology and better cognition, but plasma/serum klotho correlates only weakly with CSFâso raising blood klotho may not translate to brain klotho. (PubMed)
Bottom line for cognition: In humans, evidence supports avoiding low klotho; it doesnât show that pushing alreadyâhigh serum klotho higher leads to more brainpower.
Does âmore klothoâ slow human aging?
- Mortality: Several population studies link low klotho to higher allâcause mortality. Importantly, a large U.S. cohort showed a Uâshaped curve: the lowest and the highest klotho groups had higher mortality risk than the middle. That argues against âthe more, the better.â (PMC)
- Longevity genetics: In very large cohorts, KL variantsâincluding the KLâVS haplotypeâdo not robustly associate with living longer, further tempering the longevity claim. (PMC)
What animal data do (and donât) say
- Nonâhuman primates: A single low dose of recombinant klotho improved working memory in aged rhesus macaques; high dose did not. That suggests an invertedâU, doseâsensitive biologyânot âmore is always better.â Translation to healthy humans is unknown. (Nature)
- Mechanism hint (platelets/PF4): In mice, klothoâs cognitive effects appear partly indirectâit raises platelet factors (notably PF4), which then act on the brain. This is promising but preclinical. (Nature)
Safety and physiology considerations if you tried to raise it anyway
- Mineral metabolism: αâKlotho is the coâreceptor for FGF23 and helps govern phosphate/vitamin D handling. Overâactivating this axis could, in theory, push toward phosphate wasting and bone effects. Assay and context matter, but the biology argues for caution. (Frontiers)
- Formulation matters: Different klotho forms behave differently in animals; some engineered forms that strongly drive the FGF23 pathway lowered serum phosphate and calcium, underscoring that âraising klothoâ isnât a single thing and could carry tradeâoffs. Human safety data are lacking. (Nature)
- Clinical-stage therapies: As of now there are no approved human klotho treatments for cognition or aging. Gene/protein approaches are in preclinical/early development for neurological disease, not for healthy people. (PMC)
Practical takeaways for your level (â1123 pg/mL)
Youâre already high. Population data donât show further cognitive benefit above this range, and one large cohort hints that the very highest levels might not be ideal for survival. I would not try to push it higher on purpose. (PMC)
Focus on maintaining, not amplifying. If you want to support brain health via klothoâfriendly, evidenceâbased levers:
- Exercise regularly. RCTs and metaâanalyses show endurance/interval training raises circulating klothoâwhile independently benefitting brain and vascular health. (PubMed)
- Mind the FGF23âphosphate axis. Keep kidney health optimized; avoid chronic high phosphate additive intake (processed meats, cola/processed foods), which is tied to adverse FGF23/klotho signaling in experimental work and CKD contexts (extrapolation, but low risk). (PMC)
- Measure carefully. Klotho assays vary; repeat measurements (same lab/assay, similar timing) and interpret alongside kidney function, minerals, and vitamin D. (Frontiers)
If pursuing interventions, do it in trials. Experimental klotho therapies are being developed for diseases (e.g., ALS), but not validated for healthy cognitive enhancement or antiâaging. (BioProcess International)
Why this conclusion?
- Human observational data: benefits concentrate in raising the low; little sign of incremental gains above the upperâmiddle range. (PMC)
- Human genetic/causal data: do not support the idea that lifelong higher circulation of klotho reduces dementia risk or broadly raises intelligence. (Nature)
- Animal data: show potential, but with doseâsensitivity and mechanisms that may not require pushing serum klotho to very high levels. (Nature)
- Risk balance: A Uâshaped mortality association argues for moderation rather than maximization. (Frontiers)
If youâd like, I can map your result to the specific percentile for your age and assay and suggest a monitoring plan (labs to pair with klotho and how often).
1 Like