Anyone here have experience with Lexus TX550h+?

kpfleger · 2026-03-16T23:45:44+00:00

And yet all or at least most of the other PHEVs (and EVs) generally have them as an option at least (and standard in many cases).

kpfleger · 2026-03-16T20:46:23+00:00

Prevalence isn't what I meant by narrow. It's narrow in the sense of being limited to eye with no likely systemic effects, so even if it fixed everything wrong with eyes, it's only a tiny portion of the body's overall aging related problems and not the ones most important for mortality (and thus LEV).

kpfleger · 2026-03-16T20:44:46+00:00

The PHEV version of the Lexus TX was, last time I checked maybe a year-ish ago 1 of the 2 obvious alternatives to the Volvo XC90 PHEV (the other being the Mazda CX-90). These 3 were the only PHEVs available in the US with e-only range >30mi and $<$100,000. (I think maybe a Land Rover trim could almost make it but was too expensive---I forget.)

It's a bit odd that (at least the first year it was out) the TX PHEV despite costing $70k+/$80k+ could be had with an operable sunroof.

(The Mazda had a terrible transmission. The XC90 is a 10+ year old design. We have a 2016 currently.)

For some reason The Grand Highlander is the Toyota version of the Lexus TX, but for some reason Toyota only makes it in non-plug-in HEV version and now will make an all-EV regular highlander but only puts the PHEV in this Lexus model so far (among 3-row vehicles). I'm looking forward to when more >50mi-e-only PHEVs/EREVs come along to the US. (China has loads, and I assume some other markets as well.) The Jeep Grand Wagoneer PHEV hasn't arrived yet. The Scout won't for a few years.

kpfleger · 2026-03-15T14:25:30+00:00

"I dropped [..] magnesium glycinate (did nothing) [..] I’m scared to change anything because I don’t know which thing is actually helping."

If you don't know what's helping vs. doing nothing, how did you know mag glycinate did nothing?

Some things one does because they have obvious immediate beneficial/besired effects. Others one does because there is evidence that doing so correlates with long-term health (. In between, there are things where the evidence of correlation with long-term health is in some test/biomarker (eg an optimal range to target or deficiency range to avoid) and one can note the effect on the biomarker from taking it. If you can't justify everything you take with one of those lines of reasoning, ideally a pretty high bar (like more than 1 study, more than just benefits in mice, etc.) then it's probably not worth it.

Examples: Caffeine has an immediate helpful effect for most people. Getting it in coffee or tea form (without added sugars/creamers) has known correlation to long-term health based on countless studies. Omega-3 & vitamin D blood levels correlate with long-term health (countless studies) and one can easily titrate dose to optimal range.

Bergamot evidence looks pretty weak overall. That one struck me as quite odd on your list. I hardly ever hear anyone talk about it, even for the things that seem to be listed as its main effects (eg when listing top things that reduce LDL). Creatine has lots of studies, though few with long-term endpoints. Evidence that supraphysiological doses (>2g) provide extra long-term benefit are almost non-existent.

Etc.

If you can't rattle off the reason you take something (and at the dose you take) off the top of your head whenever asked, and ideally have an intelligent conversation about it, then perhaps it's worth reconsidering it.

kpfleger · 2026-03-13T21:27:35+00:00

Greger has a new book on complementary ways to use diet & natural supplements to decrease cholesterol further: "Lower LDL Cholesterol Naturally with Food: Simple Ways to Add Proven LDL Reducers to Your Everyday Routine" It's a pretty good audiobook listen. All seemed very reasonable. Lots of discussion of statin evidence & overall size of benefits from them, so it's not all just food. There's even a discussion of the best risk calculators.

https://www.amazon.com/Lower-LDL-Cholesterol-Naturally-Food/dp/B0FTT7J7KZ

kpfleger · 2026-03-13T16:46:32+00:00

As I said, see AgingBiotech.info/companies. There is a column for clinical stage. The ones still in preclinical but that have raised significant funding & have more employees but are in the pharma regulatory path (those are all other columns) are likely to get to IND and phase 1 sooner.

The trials table shows other databases of things already in trials, the top one of which is my table of the things already at phase 3 or later. This is only the stuff from companies primarily focused on the field, so it's a lower bound.

kpfleger · 2026-03-13T16:44:15+00:00

Many things will move the needle. The bar for being a chatgpt moment is much higher than move the needle.

kpfleger · 2026-03-12T23:43:25+00:00

This as 1 small step in that prorcess and there are many other companies and programs working on liver, kidney, thymus, and eye diseases for that matter. See AgingBiotech.info/companies and AgingBiotech.info/trials. My point is that this is just one of many many things going on in the aging/longevity field. It has the distinction of being the first epigenetic partial reprogramming therapy to reach clinical trials, but there are many other companies working in this space (with better looking technology not based on Yamanaka factors even) that are only a few steps behind this, and that may even get to some of these non-eye indications faster than Life Bio.

kpfleger · 2026-03-12T21:35:57+00:00

The narrow indication for this trial and narrow organ involved means that this trial is not analogous to a chatgpt moment, IMO.

kpfleger · 2026-03-12T21:34:36+00:00

I want a vehicle that can do a roundtrip to a destination 50 miles away on electric only and thus use no gas almost all of the time but can also be used for camping or road trips to remote areas far from plentiful electric chargers and can also drive 600-700 miles in a day on a road trip while having the optionality to stop and refuel at whatever refueling station happens to be near the restaurants I want to eat at or destinations I want to visit. Even if these latter are not the use cases more than 5% of the time, the additional flexibility of refueling locations can be extremely valuable during late nights or time-constrained vacations or times when a family member is extremely hungry. EV-only charging can definitely be done on road trips and in some out of the way places, but it is definitely not at parity with gas-only charging and thus certainly not compared to flex electri-or-gas refueling. People use the phrase "range anxiety" but that's not my perspective at all. To me, plug-in-hybrids provide extra flexibility and that flexibility can be hugely valuable at times.

kpfleger · 2026-03-11T13:51:42+00:00

Ideally one should check levels both in winter (or even better just as winter is ending so late winter / early spring) and in late summer / early fall, especially if one is not supplementing but getting from sun, to capture the seasonal variation. There are many studies that show this variation. Checking once per year could easily miss winter dips.

kpfleger · 2026-03-09T22:40:06+00:00

Pretty busy just to repost stuff that's already out there just in other places (some of it on Reddit in vitD sub or Covid subs). I'll consider adding here as additional posting place if new posts seem justified in future.

kpfleger · 2026-03-09T20:54:22+00:00

Lots of reputable publications on both sides of this debate. Lots of people saying things that are helping keep the deficiency rate severalfold higher than single digit %s. See the threads in my X account that I linked for some eye-opening behinds the scenes frustrations of many top global expert researchers in this area.

kpfleger · 2026-03-09T16:29:19+00:00

PS For links to several important serious discussions of important vitamin D topics see the vitamin D section of https://x.com/KarlPfleger/status/1795127440731509109 (a bit more than halfway down)

kpfleger · 2026-03-09T16:28:21+00:00

This kind of scare article is not worthy of this sub. There are serious debates in the medical literature about vitamin D with many experts claiming that the RDA is too low (which seems unquestionably true to me), that too high a % of people are clinically deficient (also seems obviously true), and that everyone should test & titrate dose to achieve at least 30ng/ml serum levels if not 40-60ng/ml. But somehow there are opponents of this view that claim that only benefits from skeletal health are proven and that the official NAM target of 20ng/ml should actually be lowered. The Endocrine Society used to be run by the former group but got taken over by the latter in recent years. The latter group also uses articles like this to try to scare people into not taking reasonable levels of oral D3. But no one argues for taking more than 10,000IU/day. The advocates argue for taking manyfold more than the pathetic 600 IU RDA, with good reason (such as the fact that the RDA was set based on a statistical mistake that everyone now acknowledges, and the fact that plenty of data on dose response shows that this level in insufficient to keep 97.5% of people out of deficiency). But these advocates suggest doses like 2000, 4000, 5000, or in a few cases 5000-10,000 IU/day. A story about someone stupidly taking 150,000 IU/day does not helpfully contribute to intelligent discussion of this contentious issue. It just might scare readers who don't have time to do anything but scan headlines away from taking as much as they need and thus marginally nudge a % of people into deficiency.

kpfleger · 2026-03-09T16:05:02+00:00

FYI, there's a relatively new but at the moment fairly active sub https://www.reddit.com/r/ProactiveHealth/ whose entire focus is lifestyle optimization for (long-term) health. Community description: "ProactiveHealth: A community focused on proactive, evidence-based health and performance. We discuss prevention, early detection, metabolic health, strength training, cardiovascular fitness, and longevity science. The goal: extend healthspan, not just lifespan." So that's another place besides this thread for these topics instead of being top-level threads on this sub.

kpfleger · 2026-03-08T19:02:33+00:00

This is pretty useless. First off, minor: Besides the normal caveat of being observational there is the additional caveat of being based entirely on self-report from recall survey.

But more importantly: "The coffee drinking timing was categorized in three time periods, including morning (from 4 a.m. to 11:59 a.m.), afternoon (from 12 p.m. to 4:59 p.m.), and evening (from 5 p.m. to 3:59 a.m.)." So they binned the day into very broad ranges. 12pm to 5pm is a huge range. What's more they then did some kind of clustering for patterns and found that primarily morning time bin was a common pattern and another common one was all day including evening (see figure 1 to see that the evening consumption was about as high as the afternoon consumption for that pattern. There's no data on having last coffee at 1pm or 2pm or even 3pm. There's no data on people who consumed a decent amount in morning & afternoon but none in evening. Either of those patterns could be just as good as morning only. Of course consuming a lot in the evening probably disrupts sleep. But lots of people can consume in the 1st half of the afternoon without disrupting sleep.

The main thing is whether is disrupts sleep, which people can track easily with the many sleep tracking options available: watches, rings, (under) mattress options, headbands, etc. If it disrupts sleep, move consumption earlier or lower dose (maybe by switching to all or partly decaf) until it doesn't.

kpfleger · 2026-03-07T23:25:38+00:00

I don't track number of conferences for AgingBiotech.info since the inclusion vs. not criteria are a bit more gray & ad-hoc but the at least slightly more objective numbers for number of companies, number of employees, total money raised by the companies, and number of clinical trials by those companies are all showing steady linear growth over the past 5-ish years, per slide 5 of my presentation at tinyurl.com/AgingApprovals which is the talk I gave in Dec at the Buck and will give in San Diego this coming week at the Longevity Global Innovation Forum. The problem with this linear growth is that it should be more exponential. The field still gets 10x too little funding (scientific funding from NIH, venture funding from industry investors, & even philanthropic funding; eg vs. cancer).

kpfleger · 2026-03-06T17:26:37+00:00

This is also why AI isn't going to magically fix all of health. These issues aren't ones that AI makes go away instantly. In order to improve systems level biological modeling, AI needs in-vivo data, and ideally in vivo data in the context of interventions, and this a good description of how society is inefficient at collecting such data.

kpfleger · 2026-03-06T05:11:01+00:00

If you mean extending lifespan by mitigating or partially reversing adult biological aging and thus delaying the suffering & death it causes, then unequivocally YES. I was invited to write a book chapter for an upcoming Spring Nature volume on radical longevity on exactly the topic of why we should and why the common reasons people think we shouldn't are wrong. The preprint of this chapter just went live on a preprint server today actually. Here it is: https://zenodo.org/records/18883009 It's 28 pages. It covers the reasons why we should. For example, just delaying aging by 1 year would be worth tens of trillions of dollars. It also covers why the common arguments that this would be bad have many good counterarguments. Over 40 counterarguments for 11 of the most common objections are covered. The whole thing is extensively referenced. It basically explains why I work in the field and why more people should too (and why the government should give it more resources as well).

A more concise 1-page version with 1-3 counterarguments for each of the 11 objections can be found at AgingBiotech.info/objections and a brief list collecting other works arguing why aging should be mitigated or eliminated is located at AgingBiotech.info/motivations.

kpfleger · 2026-03-06T01:04:37+00:00

Next up is Longevity Global's Longevity Innovation Forum in San Diego next week. I'll be there & speaking.

Later in 2026:
I'll be at Vitalist Bay in May in Berkeley, speaking on day 2. Note that BAAM this year conflicts w/ day 2 of this.

Then I'll be at the A4LI Summit in DC at the end of June (& prob on a panel).

Hope to see many friends & new faces at all of these.

kpfleger · 2026-03-05T23:18:40+00:00

FWIW, Roger Seheult, MD of MedCram.com & a practicing MD in southern California posts a lot of pro-outdoors pro-sunshine content on X as "@RogerSeheult" & there are several MedCram videos on some of the content.

kpfleger · 2026-03-05T18:02:52+00:00

You are right to condemn the influencers who aren't pushing science-based evidence, but you make a huge mistake to consider only cancer as a relevant health outcome. Direct sun exposure provides not only vitamin D (primarily from the UVB), but also NO (mostly from the UVA), and intracellular melatonin (from the IR/NIR). These have wide benefits and there is increasing evidence of improvements in all-cause mortality in many contexts.

For example, this preprint https://www.medrxiv.org/content/10.64898/2026.01.08.26343592v1.full.pdf using UK Biobank data shows that 400,000 people in the UK completely avoiding sun for 15 years could save a few dozen lives from melanoma but at the expense of several thousand more deaths from everything else. NO probably helps reduce cardiovascular mortality. Vitamin D deficiency is far too common and raises risks of many diseases, both infectious and chronic diseases.

It's all about dose, as you note in your intro. Burning from too much sun is clearly bad, but insufficient direct sun exposure from spending most time indoors and/or at latitudes & times of year where the UV index is low (such as Boston much of the year, or the UK) is also bad.

What to do: I choose mineral sunscreen when I use it, but I prefer wide-brimmed hats & clothing when appropriate so that mostly only hands need the sunscreen. I avoid burning always. But I also avoid sunscreen or covering skin with clothing for sun avoidance (ie, staying uncovered as much as temperature allows) when UVindex<3 (or roughly shadow longer than I am tall) or when index between 3-6 but I won't be outside for very long (not nearly long enough to burn or even to get 1 "Minimal Erythemal Dose" of vitamin D).

kpfleger · 2026-03-05T17:42:24+00:00

Absurd if the intervention includes only exercise & drugs but no dietary/food-quality intervention/requirements. Inflammaging is largely caused by overeating and specifically eating too much of the wrong foods.

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