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kpfleger

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  1. Don't forget that that applies only to some of the interventions these companies are working on. CR and other lifestyle habits at most slow aging relative to population average. They don't stop it. So many of the anti-aging efforts will be important to even those on the most optimal levels of CR. CR in humans probably slows aging by at most 30% (and that's probably wildly optimistic). Senolytics, partial epigenetic reprogramming, stem-cell therapies (which may work through signaling that does reprogramming), therapies to protect mitochondria from damage, persistent AGE cross-link breaking, immune system regeneration, etc. will all probably be beneficial to even those on CR.
  2. Thanks, I hadn't seen those. There were only ~26 companies mentioned (vs ~110 that I already had). There were a couple new to me so I added them to the sub-tab of my table that has companies to consider adding when I get a moment. In some ways the site I made is the answer to the site he said at the top of his part-ii post that he couldn't find anywhere. And my counts sub-sheet answers some of the money questions he lays out in his first paragraph (of part ii). I added a comment to his post but it's waiting for him to approve it.
  3. I made a website to track all aging/longevity companies, in an interactive (sortable, etc.) and quantitative way: agingbiotech.info The aging/longevity field has grown to where it's hard to follow. There are books, journals, blog, some industry reports, and a few website with forums like this one, but few structured info sources for broad context or targeted queries, particularly few focused on aging defined as the underlying molecular causes of multiple age-related diseases. The web had no comprehensive & precise list of companies with therapies or diagnostics for underlying aging in this sense. Hope this is helpful to some. For those here, it's particularly worth noting that many interventions being pursued within the aging/longevity communities (both in academic labs and companies) are focused on correcting or making up for age-accelerating factors, either genetic disorders that accelerate some aspect of aging or lifestyle factors that do so such as bad diet, lack of exercise, etc. including their downstream manifestations such as obesity. There is even a new buzz-phrase that succinctly describes a subpart of the field focused on these kinds of things: metabesity (with a conference this month in the DC area even). Interventions that are best categorized into this bucket include category buzz-phrases like CR-mimetics, exercise-mimetics, Rapalogs, etc. Metformin probably goes in this bucket. For those on a CR diet, or even just eating high micro-nutrient, obesity-avoiding, relatively healthy diet (much healthier than average Westerner), there is a question about how much such interventions will do to improve health & healthspan. The website includes companies working on such interventions, but also many working on things that should be important even to those on CR or living close to optimal long-term-health preserving lifestyles. Figuring out the exact boundary of that split is debatable and will only be answered definitively with further science so until then you have to decide which companies and which of their clinical trials are more worth paying attention to than others. But there is certainly important work being tracked. Hopefully this site is a useful way to check out the current state every now and then. Feedback welcomed (see contact link at the site). Karl
  4. Yes, I saw that he wrote an long post about it, didn't notice any discussion of FOXN1 nor of error bar methodology for small n use of methylation clocks (but I didn't read the whole thing carefully after seeing no discussion of FOXN1).
  5. There is a lot to like about Fahy's trial and a lot to dislike. The main 2 points made in this thread so far are both right: (1) It's nice to have this data in humans despite the obvious negatives of small n and uncontrolled and (2) the press regrettably but predictably over-hyped its coverage. Let's move on from those points and let me add a few other points that haven't been brought up in this thread: I'm disappointed that Fahy thought that the right order in which to do this science was human n=1 trial followed by uncontrolled human n~=10 trial without any work in mice or any other mammal. The thymus involutes in mice too. A controlled mouse trial with much larger n could have been could have been done for less than (I presume) the cost of the n~=10 human trial, and it could have included followup for a long fraction of mouse lifespan to watch for long-term negative effects (or even been a lifespan study with similar total real-time study duration, eg, start with 2-year-old naturally aged mice like the Oisin trial and follow until death roughly a year later). A big question in this work is how long will the regenerated thymus remain more effective before re-shrinking. It's possible the negative effects of GH/DHEA are not so bad if only pulsed every 5 or 10 years, but if the thymus recovery is very short-lived then that is much more worrying. Followup with scans multiple years later will be very important. (And a mouse study would have been because this could have been tested on timescales relevant to how quickly the thymus shrinks in that model organism.) Fahy is attempting to commercialize this protocol to make it available as widely as possible as quickly as possible through the company Intervene Immune. Good luck to him and his team! They observed that FOXN1 was up-regulated as one of the consequences. FOXN1 is known from other work to stimulate thymus growth. Repair Biotechnologies (disclaimer: I am an investor) is working on thymus regeneration more directly via FOXN1 upregulation (via gene therapy). If all the benefit observed in the TRIIM trial is through the intermediate of FOXN1 increase,. then other direct interventions through that can avoid the HGH/DHEA/etc. Clearly an important space to watch in coming years. A lot was made about the Horvath age-clock reversal. Morgan Levine (former Horvath lab member now Yale professor doing great work on pushing methylation clocks forward) has said that she believes that though DNA methylation clocks are useful on a population level, she thinks they are too noisy on an individual level for changes in the age they report for an individual across a time interval to be reliable. She thus believes it's not useful to have one's methylation clock age tested and then retested after an intervention. If this is right (and she's clearly an authority), then it's not clear for n~=10 how much change you would expect to get due to random chance. Presumably Horvath himself could characterize this math but I haven't seen that done and presented for comparison to these results. I didn't read the paper directly. Did it present error bars on its Horvath clock averages (and cite the data and methodology by which they were computed)? Karl
  6. TomBAvoider, Michael Rae's post that started this thread provided a pretty long list of links that look pretty scientifically respectable. That post by itself seems to disagree with any claim that this is all hype hype hype. I come at this with default skepticism about the therapeutic effects and view those as just bonus if they do exist. To me this is the long-awaited successor to the Zeo headband, the first sleep measuring device that actually had EEG. This and its Philips competitor (which seems to require regularly replacing something consumable and thus seems less desirable to me) are the first sleep things that can potentially do a reasonable job at sleep phase classification. After a big analysis of all the best sleep things on the market a couple years ago, including taking 2 of the same model of one of the best devices and measuring them against each other) I concluded that movement + pulse and the other things one gets easily from wrist-based on under-mattress type sensors are just not going to be able to classify sleep phases accurately. I default assume that this will be more accurate than the Oura ring, any watch, or any ballistocardiography device. I think this is a reasonable default position until data says otherwise (rather than requiring data to prove this). Even if it's not perfect and classifying deep vs. shallow vs REM perfectly, the EEG should mean it is better at hitting sleep vs wake than the other categories of device. Why is good passive recoding of sleep important without therapeutic effect? Because there are dozens of known ways to influence sleep quality (blue-light blocking glasses, get bright light during the day, don't eat late, keep bedroom dark, keep bedroom cool, just go to bed earlier, etc.---just Google sleep hygiene, or if more time read Why We Sleep by Walker). A tool to measure how you are doing and track that over the years as you age and sleep quality naturally gets worse with age is useful to help dose doing all of these things. Karl
  7. Dreem2 headband is now on sale for $500. This appears to be the summary list of changes from Dreem 1.
  8. This is surprising: the study did report results at finer-grained breakpoints (8 sleep ranges instead of 3), but it was not a U-shaped curve with mortality. The lowest and highest sleeping groups survived much better than the 2nd lowest and 2nd highest, and not that much worse than the groups in the middle ranges (with confidence intervals that don't go way into bad territory so it doesn't look like just randomness due to low n). The differences between adjacent groups may not have been statistically significant, but when graphed the overall 8-group bar-chart still represents a striking departure from what you would expect for a U-shaped dose-response (see attached bar chart, fig 1 of the paper). In numbers, those sleeping >7.5hr (n=15) had 89% survival (95% CI 81-91%) vs those sleeping 7-7.5hr (n=31) having 58% (45-71%). The 81-91% range for >7.5hr doesn't seem that much worse than the 85-94% CI for the pooled 5-6.5hr group. If this were some weird quirk due to the low n, I would expect a bigger CI that ranged down further into bad survival %s. I didn't see any discussion of this turning down of the ends of the U curve in glancing very briefly through the later parts of the paper. But this doesn't match any of the other sleep research I've ever heard about. It seems so odd, it's hard for me to take this paper as a reason to think that >6.5hr is the point at which more starts to become bad, as suggested by their pooled 3-group analysis (and the figure 2 that Ron posted above). So until I see some study that replicated this, I'm still going to go with 7.5hr of actual sleep measured by a tracking device as the rough amount where more sleep may start to become a negative, as suggested by the hunter gatherer research reported in the Walker book and the studies described by Parsley. My own sleep averages around 6.5hrs (measured w/ Emfit QS under mattress + Garmin Fr235 at wrist). Karl
  9. Ron, thank you for the https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010336/#!po=1.21951 study. This is the best direct answer yet to the question I posed in the 1st post. As Michael said, it will be some time before we have lots of studies using actual sleep measurement and long-term health followup because we didn't have measurement a long time ago and what measurement we had (sleep studies) were very sleep disruptive. We obviously didn't have FitBits and Apple Watches in the 1970s, but even if whatever wrist actigraphs we did have were systematically different than what people use now, it is clearly a strict improvement on self-reported time-in-bed, and the study demonstrates exactly what I hypothesized in the 1st post: It's notable that getting too little sleep is much worse than getting too much, based on the pasted graph. It seems odd that the highest breakpoint they used was 6.5hrs. Given the other science suggesting 7-7.5hr as optimal (the studies Kirk Parsley described in the linked podcast above) or 6-7.5hr as optimal (some of the modern hunter-gatherer studies described in Matthew Walker's book I recommended above), it seems strange they wouldn't separate the above 6.5hr group with a breakpoint at ~7.5hr. I haven't had a chance to read the paper yet, but will look at this when I do. Maybe there weren't enough subjects in the above 7.5hr range. But if there were, one hopes their outcomes don't drag down those in the 6.5-7.5hr range. Tangentially, I note that Dreem's website homepage says the Dreem2 is available now, but when you click through to the order page, it still says not available yet and has a place to register your email to be notified when that changes. Karl
  10. FYI, 2nd generations of the Dreem and Philips sleep enhancing headbands announced/shown at CES this week: https://www.usatoday.com/story/tech/columnist/2019/01/08/sleep-tech-ces-2019/2505688002/ ...along with a new 3rd sleep enhancing headband called Urgonight from another French startup, this one interestingly designed to be used during the day in order to enhance slow-wave sleep at night. The USA Today article I happened upon didn't include references to scientific studies supporting the idea the way a post from Michael would. 🙂
  11. Great find Michael---thanks for sharing. All cause mortality would be nice instead of just CVD. Is there a price in terms of increased diabetes or dementia, or increased death from infectious diseases?
  12. kpfleger

    Cadmium contamination in cacao products

    It's true that I expect both the bad heavy metals and the good flavanols to vary and CL doesn't explicit address this variability that I noticed. I'm sure it's expensive to run the lab test and thus to test everything multiple times to get a range would be harder. It'd be nice if they tested some example products multiple times (eg buying national brands in different geos and over different seasons and showing a distribution to get a sense of the kind of variability) but I haven't seen it if they have done this. Still, they do often test the same products in different years and I trust them a lot more than I trust some customer service representative from Trader Joe's. In fact, they tested Trader Joe's unsweetened powder and found it exceeded acceptable thresholds in both 2014 and 2017 (1.2+ mcg cadmium / g of powder both years). I don't know what their quoted "ppm" means in this context but either it's a misleading metric or their quality control isn't as good as the rep claims. Navitas Naturals nibs only had 0.32mcg/g of cadmium. Since Trader Joe's 85% bar had 0.73mcg/g (vs Endangered Species 88% with 0.06mcg/g and several other bars with low levels), this doesn't seem to be an issue isolated to their powder. I personally will stay away from Trader Joe's branded chocolate, at least until they improve on future updates of these reports.
  13. One more with evidence of making flu vaccine more effective: ginseng: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659611/ (but also a study just in mice) Still, add this to AHCC and Rapamycin (and maybe fasting/CR). And probably sleep around the immunization is important too though I haven't seen a study on that, but intuitive given the other reading on sleep and immune system. Note: Timing is different for each of these. Eg, AHCC was given for a few weeks after immunization vs. Rapamycin was given for weeks but stopped 2 weeks before vaccination.
  14. I believe the science showing immune boosting of healthy sleep (equivalently the immune compromising of lack of sufficient sleep) is more compelling than for cold exposure, and probably more compelling than for exercise, so I'd put the list as healthy diet & sufficient sleep, then moderate exercise, then if you want to include it (not a topic I've dived into personally yet) cold exposure. Eg, see the sleep book I recommended IIRC in another thread recently: Why We Sleep by Walker. But it's probably easy to find primary studies too.
  15. I read a bit about why it didn't work in previous years. The short version is that it has live but weakened viruses, multiple strains. They have to carefully balance the strains so that some don't get outcompeted in the body and thus not provide protection by not being present in sufficient number for an immune response to be learned. For a few years one of the strains got out of whack and outcompeted some or all of the others. They think they've fixed this and the CDC is convinced this year based on data so far, but the AAP is not convinced and wants to wait until the data is more numerous and so these 2 orgs recommendations don't agree on this form of the vaccination this year. But even AAP agrees that the mist is better than not getting either form.
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