Extending lifespan (lessons from the ITP)
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- Опубліковано 21 лип 2024
- Video sponsor; Longevity.Technology - longevity.technology/?...
The Interventions Testing Program (ITP), funded by the National Institute on Aging, are testing different inventions to see if they prevent disease and extend lifespan in mice. The main goals are to provide preliminary evidence on compounds that have translational potential for human use to increase healthspan as well as to further understand the aging process through the protein targets of the compounds they identify as being effective. Since the initiation in 2003 and the testing of more than 40 compounds, 7 compounds have been identified to be extending the mouse lifespan significantly. However, this is to varying extents and some show sex-specific effects. So, in this video I will explain the lessons we can take from the ITPs work so far, take a look at their key principles, including their genetically heterogeneous mice, to ensure validity of
their results, and then the compounds that have been shown to extent lifespan, have no effect or are yet to be published.
TIMESTAMPS:
Intro - 00:00
What is the ITP? - 00:45
Key principles - 02:45
ITP experimental design - 05:40
7 compounds - 06:40
No extension/still being investigated - 13:30
Human translation? - 14:49
Outro - 14:00
REFERENCES
Mouse Phenome Database - phenome.jax.org/
ITP website - www.nia.nih.gov/research/dab/...
Nice review (The road ahead for health and lifespan interventions - doi.org/10.1016/j.arr.2020.10...
Latest ITP update - doi.org/10.1016/B978-0-12-815...
Rapamycin dose-dep - doi.org/10.1111/acel.12194
Glycine paper - doi.org/10.1111/acel.12953
NDGA paper - Tezil, T., Chamoli, M., Ng, CP. et al. Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy. npj Aging Mech Dis 5, 7 (2019). doi.org/10.1038/s41514-019-00...
Check out the latest video by @LifespanNews • The Dog Aging Project ...
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So, what compounds would you like to see tested by the ITP?
xylitol, but I don't know if it would be toxic to mice (it is to dogs).
I have not watched your video yet, I will do so when washing dishes later today, am looking forward to it, and there's another in my queue from NUS on reproductive aging - something about ants. I'm going to try to guess the list - acarbose, metformin, rapamycin, that estradiol derivative? analogue?, maybe spermidine... hmm... can't think of the other; I would say glucosamine or hyaluronic acid but I don't think those were either tested or found to be efficacious by ITP. Can't wait to wash dishes and find out ;)
I came across something interesting about sacoglossan sea slug regeneration and maybe you would be interested in it; researchers cut the heads off the poor things and three of the 16 regrew their bodies (and one of the three managed to do it a second time). When I told my family about it they had two great questions - how do the slugs manage to have enough resources to regrow their bodies - the researchers stated it may relate to their photosynthetic ability derived from chloroplasts from the algae they eat. Second question was whether the new body's age is younger or the same age as the head - no info on that. I would post a link but YT is deleting a lot of my comments when I cut/paste or use external links.
@@rhyothemisprinceps1617 cool, thanks, and yeah, i miss a lot of great comments as youtube remove them!
doxyclycine or minocycline? would like to see those tested if they have not been already.
And lovastatin, due to its effect on NO.
Interval training. Their limit on only compounds rather than the whole package is underwhelming.
ISRIB.
My favorite thing about this presentation is what you pointed out about how rapamycin is shown to increase incidence of cataracts and/or testicular degeneration. A close second is how metformin has no significant effect on aging when administered alone, but greatly boosts the longevity benefits of rapamycin when administered alongside it. People are very eager to learn of compounds which might slow aging or even lessen biological age, and are even willing to ingest agents at the first hint of promise. The things I cite/appreciate here, however, go to show just how much gamble is involved with that. A chance gain easily can be accompanied by an unexpected loss. And even if an agent is shown to have only positive benefits, you can't know that this will continue to hold true when it's mixed with an agent which wasn't a part of the study. Eat well. Fast and supplement in an informed way. Exercise wisely. Get adequate rest. Avoid stress. Live life with a sense of purpose and adventure. Laugh a lot. These are the things which promote longevity. Leave the guinea-pigging to the actual guinea pigs. Thank you for making caveats a key part of all your presentations.
Thanks again for the video. I must say I absolutely love how rigorous this study was!
The info you want starts at around 7:30.
Thank you. Your presentation is just science with no anecdotal evidence and no wishful thinking. This is very hard to find for people who are not medical professionals. Keep up the good work.
Aging is the biggest risk factor for old age. It’s absurd that they won’t treat old age as a disease.
They are.
wow I'm watching your sub-count rise like crazy; you'll be at 10,000 in no time.
Always edifying content on this channel.
Great video! Thanks for keeping us updated on this research. Glycine is a supplement I have been taking for years. I will look into it more. Looking fwd to your next video.
@Life & DIY Hey Lovely!🙆🏻♀️🌟💜
@@chersworldchannel Cheryl! Too funny we keep finding each other on the same videos! 🤗
Sheekey, Do you take any special compounds such as NR, NMN, etc?
I wonder how soon we will have highly reliable, affordable, and accessible treatments or over the counter options for aging, and extending both healthspan and lifespan. I hope it is soon because I want my mother to be able to benefit from such treatments (and she is 64 years old, prediabetic, arthritic, asthmatic, and obese).
My parents are 68 and I've convinced them to undergo NAD+ IV therapy like I did for drug dependency two years ago, when they are vaccinated. I found out through experience that NAD also has incredible rejuvenation effects. It's expensive though. A nasal spray, powder or pills are also options.
Great as always.
Thanks!! 😊
Pretty sure that the Protandim that was tested is different than the hodgepodge of herbs sold now. The company used the same name to capitalize on the research.
@Sheeky , can you please answer my question regarding resveratrol ?
Sheekey, are you considering a video on exosomes' effect on longevity?
I wasn't..., should i? 😉
What are your thoughts on the issue of the severe telomere mutations shown in all laboratory mice breeding groups? Since nearly every "strain" has been effectively bred from a very small group of females with this mutation type. Do you think this has a significant effect on these kinds of studies?
Bret Weinstein has a much better explanation for it tho.
Yes, is a problem especially in terms of human translation. The ITP try and take this into consideration by using their genetically heterogenous mice but comes to a cost/logistics issue..all a bit of a trade off
I know mice studies are a necessity, but they do not seem to be a good proxy for humans. When calorie restriction was examined in a short lived species ( like mice, they were mouse lemurs), we saw an approximate 50% increase in lifespan. When it was examined in longer lived species (monkeys), I recall that we saw little or no increase in lifespan in one study and up to a 10% increase in another study. Therefore, we should not expect a dramatic benefit that occurs in mice to transfer over to humans.
does acarbose blunt glucose rise from fruit?
I would very much like to test Cdc42 inhibitors (CASIN (Cdc42 activity-specific inhibitor), niclosamide, Pyrvinium); Arachidonate 5-lipoxygenase inhibitors (zileuton); Rho-associated protein kinase (ROCK) inhibitors (Fasudil, Thiazovivin). Especially their combinations. in The Interventions Testing Program (ITP)
Why the interest in g protein signalling!?
@@TheSheekeyScienceShow Glycation?
Interesting.
great
I cannot get past "testicular shrinkage" for rapamycin, and I am not even male. WTH?
Yeah pretty crazy.
Rapamycin seems pretty bullish
Can you talk about the skin aging and ingredients good for the skin
Cute mice images.
I suggest 1) a drug that increases the telomere length in all cells of the body 2) Reduce senescent cell-count because they message nearby cells to misbehave 3) Adjust acetylation and methylation in DNA and histones
Done
so they tested resveratrol and it didn't extend the life span of mice ? is that right ? does this show that resveratrol doesnot have any effect of human as well ?
Yeah, no life extension in itp study. And you can never fully translate mouse to human so ultimately the answer is unknown. Moreover, the itp focus initially on lifespan, not healthspan so there could still be benefits to resverstrol
@@TheSheekeyScienceShow Thanks Sheekey
Resveratrol has some interesting activities part from effects on SIRT1 which might be more relevant to humans, at least for healthspan, e.g., it may increase PON1 activity and may prevent eNOS uncoupling. However, the activity of polyphenols seems to depend a lot on conversion to active metabolites by the gut microbiome, so your millage may vary
It depends on what type of resveratrol, and if it's combined with NMN. If it's Trans-resveratrol, and combined with NMN, and it's getting absorbed, then it's helpful. Oleic acid can also be used, or pterostilbene. I bet most of the other substances listed as no effect. Single variable testing has it's drawbacks.
NIH National Institute of Hedging?
It seems that several drugs are directly affected by the presence of testicular hormones. Do you believe that, if these drugs became the 'most popular' ones, that there would be a separate variation found for women, or that the hormones would be included in treatments?
Good question, given the evidence so far i think it's definitely possible there would be separate "most popular" supplements for either male or female. Then it would go further in terms of personalised medicine. But, initially i think it could get avoided..
@@TheSheekeyScienceShow I am a little concerned about how that would work for intersex individuals, transgender individuals, and individuals whom just have naturally unusually high or low levels of specific hormones.
@@ArticBlueFox96 me too!
I just learned yesterday that apart from the sex organs themselves, the most sexually dimorphic organ is the liver - so this may have to do with differences in how the substances are metabolized. I don't know if the liver would favorably alter function in presence of added male hormones. Women with PCOS have high androgen levels and are at increased risk of NAFLD (2x); post menopausal women are also at increased risk of NAFLD.
oh ... and the CaAKG supplement sold by Ponce De Leon (Rejuvant) has men's and women's formulas - the men's includes retinyl palmitate, the women's has vitamin D.
Proper management of mental stress has been linked with longer telemeres and longer lifespan.
DId they test senolytics?
They are currently testing periodic fisetin
@@TheSheekeyScienceShow hey thanks for the info! I love your videos
In humans females generally outlive males. Does the same hold true for the female control mice? In which case is the apparent sex advantage for males of the intervention simply a matter of mitigating the inherent disadvantage of being male, or do the treated males outlive the females?
Re the lifespan vs healthspan issue, I think it's a fairly good bet that anything that improves lifespan also improves healthspan. It's not as if these mice are being kept alive by CABG, pacemakers and dialysis.
As a men i take allways a little dose of strogen. Is very good. You feel very well. Good for skin hair libido.
It's a shame that there is no outburst like that in France 🙂
It has nothing to do with the lifespan but colostrum seems to be great for your health.
Wrong.Colostrom opens up the growth hormone gland and is totally linked to longevity .
There's a pension time bomb approaching. The powers that be don't want us living longer, so I can't imagine why information promoting extended lifespans are being allowed. Get it while you can, I guess. Keep up the good work.
Nmn. Resveratrol. Akg. Fisetin. Olive oil is my stack
Awesome content and presentation, but that pfp is weird
EXELLENT YOU .SOUND REALL SMART AND REALL CUTE!
Quit all sugar!
Iodine reduction
🗿🗿🗿Rapamycin te rapa o te whenua...aśwagandha