humans have been searching for the magic pill for Aging for eons thousands of years ago it was the Water of Life that supposedly made you young again but today is various supplements and pharmaceuticals that are touted as having longevity benefits how do you know if a supplement is going to make you live longer well you can't because it's virtually impossible to do that kind of an experiment in humans however we do have a bunch of animal studies on rodents worms and flies that have found life extension effects with different compounds in this video I'm going to go through through the findings of the National Institute of aging's intervention testing program and see what supplements and molecules they've found to work in extending the lifespan of mice by 20 30 and up to 60% so what is the interventions testing program or ITP for short it's considered the world's most rigorous peer-reviewed program for investigating longevity molecules and their effects on mice they started in 2002 so the program has ran for over 20 years and have tested dozens of different compounds you can read all their supported into ditions and Publications at the National Institute of aging's website over the 20 years the ITP has identified nine molecules that have extended lifespan in mice they are acaros aspirin canag flosin captopril glycine nordi Hydro gutic acid ndga protm rapamycin and 17 Alpha estrad that's not a very large amount of compounds from the dozens of compounds that have been tested which kind of shows that most supplements don't have life extension effects even in animals this doesn't mean that the list is conclusive either because the ITP is continuously testing new molecules so let's take a look at these molecules more closely the first one is a carbos a carbos is a diabetes drug that blocks glucose absorption the ITP studies on a carbos found that it extended median lifespan in male mice by 22% and by only 5% in female mice maximum lifespan increased by 11% in males and 9% in females this is quite interesting and you would predict that these life extension effects were because of lower ing blood sugar levels however the ITP studies done on Metformin which is another diabetes drug and also lowers blood sugar levels have found that metformin doesn't extend Lipan unless it's paired with rapamycin so it's rapamycin that does the extension effects not meformin metformin does reduce the risk of heart disease mortality in people with diabetes but it hasn't been found to have any longevity effects in otherwise healthy humans either so in my opinion the life extension effects of a carbos might have to do more with the reduction in glucose absorption rather than lowering of the blood sugar levels if you absorb less glucose you also absorb fewer calories and we know that calorie restriction is the most proven non- gentic method of Life Extension in animals does this mean that taking a carbos is going to be beneficial for human longevity a carbos does reduce the risk of heart disease and hypertension in people with impaired glucose tolerance a carbos also induces weight loss through reduced glucose absorption as well as by increasing the expression of glp1 which is the mechanism by which OIC works the problem is that a carbos also appears to to have some negative side effects type two diabetics who take a carbos see a decrease in muscle mass hand grip strength and walking speed metformin has also been seen to blunt the muscle growth signal in response to resistance training in older adults muscle mass and muscle strength are both very important for longevity and in appears that acaros and Metformin could be harmful for older people who have low muscle mass and low strength it might be that with acaros you can mitigate the negative effects on muscle mass by just lifting weights because in these studies the patients didn't do any form of resistance strange however in the metformin study the people did lift weights and they still saw the reduction in the hypertrophy response from the training so I would predict that it might happen the same with a carbos metformin has been seen to decrease V to Max an aerobic capacity as well which is a bad thing for cardiovascular function a higher V to Max is linked to longevity when it comes to acaros then acaros hasn't been seen to reduce V to Max and in one 2006 study they found that exercise combined with a carbos treatment actually increased V to Max whereas exercise alone didn't that is very interesting but obviously we would need more studies to confirm that so overall acaros as well as metformin can be life-saving for diabetics if you're otherwise healthy you don't have impaired glucose tolerance then taking these medications might have negative effects on your Fitness taking these Pharmaceuticals recreationally for ler purposes is also somewhat of a mixed bag on one hand we have the ITP results showing that a carbos works but on the other hand the human evidence suggests that a carbos can result in loss of muscle and strength but honestly I think you can mitigate it with resistance training and a higher protein intake it's the same with OIC you lose muscle because of not lifting weights and you're undereating protein personally I'm not taking at carbos I don't have any plans to take it in the future right now but I do think that it's quite interesting the next one is canag gloin canlin is another FDA approved diabetes drug that supports skinny function and cardiovascular function it also inhibits the sodium glucose Transporter 2 by blocking renal uptake and intestinal absorption of glucose in the ITP study can flow in extended median survival of male mice by 14% Kaa also increased the age for 90th percental Survival by 9% however they found no effects in female mice although their glucose tolerance still improved this drug appears to be very similar to a carbos it works through reduced glucose absorption and it improves glucose tolerance but does it have the same negative side effects on muscle growth there's no studies in humans but in mice canic Flows In does downregulate certain proteins and muscle stem cells next up we have aspirin which is a non idal anti-inflammatory drug or Nate you can get it over the counter which makes it very easily found in the ITP study aspirin treatment extended median survival in male mice by 8% but it wasn't very significant there are other animal studies as well that find how aspirin extends their lifespan the effects are probably because of aspirin's anti-inflammatory effects however in humans daily intake of aspirin has been actually seen to be linked to a higher risk of Alla morality primarily because of increased cancer related deaths this applies to elderly people who see an increased risk of cancer metastasis from aspirin treatment and accelerated cancer progression as shown by several randomized control trials there have been previous studies that found that aspirin treatment reduces the risk of cancer but those studies were mostly done on younger populations whereas the recent clinical trials were done on the elderly people and in those people aspirin treatment appears to increase the risk of cancer the reason why there's a discrepancy between younger and older people might be because of the age related decrease in the immune system older people have weaker immune systems and aspirin might modulate the immune system in a negative way that enables the proliferation of cancer more easily so it looks like aspirin isn't a good idea later in life historically aspirin has been used for primary prevention of cardiovascular disease which means preventing a heart attack or preventing the onset of atherosclerosis taking baby aspirin or small amounts of 50 to 100 milligrams of aspirin per day has been very common for decades for this reason so the question is does Micro doing baby aspirin every day reduce the risk of heart disease the American Heart Association says low do aspirin could be considered for primary prevention of AOS scerotic cardiovascular disease in adults aged 40 to 70 who are at a high risk of atherosclerosis but with no increased risk of bleeding because aspirin increases the risk of bleeding they don't recommend it for people over the age of 70 or for anyone who's at increased risk of bleeding what about secondary prevention which means preventing getting a second heart attack here daily lowd dose aspirin has more benefits and is generally recommended by the American Heart Association for people who aren't at increased risk of bleeding next supplement is glycine which is an amino acid that supports collagen turnover gathan production creatin synthesis and heem synthesis the 2019 ITP study found that glycine supplementation increased maximum lifespan in both male and female mice by 4 to 6% the mice consumed a diet comprising of 8% glycine which is quite a large amount and another 2011 study found that a diet comprising of 8 to 12% glycine extended the median lifespan of rats by 28% the rats lived on 113 weeks instead of 88 maximum lifespan also increased by 30% from 91 to 119 weeks the reason why glycine extends Lipan is thought to be because of mimicking methine restriction methine is another amino acid you get primarily from animal protein and methan in restriction has been often seen to extend lifespan in animals glycine counterbalances methan in toxicity and has been seen to have the same life extension effects as methine restriction without restricting methine that's why in these studies you see that a very large intake of glycine 8 to 12% of their diet extends lifespan in humans the evidence is obviously more limited but the average person's diet is very high in methine and it doesn't contain that much glycine muscle meat eggs dairy chicken fish Etc they're all very high in methine and very low in glycine glycine you can get from tendon Meats collagen fish skin chicken skin and gelatin powder this creates a scenario where most people could theoretically improve their longevity by balancing their methan in ratio with more glycine they would either need to reduce their methan intake or increase their glycine intake but most people would benefit from both there are no hard outcomes observed from high methan and low glycin intake but there are a few benefits that have been seen in clinical trials in older adults they have found that low plasma glycine levels are a marker of visceral adiposity independent of sex age body composition or chronic diseases serum glycine is also negatively associated with intramuscular atos tissue which is the fat inside the muscles methan in restriction on the other hand appears to reduce visceral fat in both animals and humans and glycine is also useful for other things such as collagen production for the skin and Joints glut thean production for antioxidant fence and inflammation sleep blood sugar and creatine synthesis so although we can't say whether or not glycine supplementation is going to extend lifespan in humans we can be pretty sure that most people are eating too much methine and not enough glycine that's why I'm also taking 10 grams of glycine as a supplement every day and I'm eating plenty of glycine rich foods next on the list is captopril captopril is an Angiotensin converting enzyme ace inhibitor used to treat high blood pressure in the ITP study captopril extended median lifespan of female mice by 4 to 5% hypertension is one of the most common co-morbidities in the world and it's called the silent killer that increases the risk of heart disease kidney disease and neurod degeneration if you have elevated blood pressure then you should try to normalize it as fast as possible because the longer your blood pressure stays elevated the more damage it can cause to your body ACE inhibitors have some nasty side effects which is why I think the recreational use of captopril is probably not worth it furthermore the life extension benefits in the ITP study weren't that big it was only 4 to 5% and it was only absorbed in the female mice so if you were ever going to take any pharmaceutical for recreational purposes to support your longevity then you would be probably better off by taking something like a carbos or rapamycin instead of CapTel the next compound is nordi hydro WTIC acid ndga it's a ligant found in croso Bush or grease wood in the TP study it resulted in 10% increase in Lipan in both sexes ndga is basically a herbal compound that's been seen to increase Nrf2 activation and thus reduce inflammation it's not a very common compound although it's being investigated for clinical purposes at the moment and I haven't found any supplements that have ndga in it so that's pretty much all I have to say about this compound prandom is another herbal supplement that contains a patent and mix of five herbal ingredients that support nf2 activation it has termic root green tea milk thisle bopa moneri and ashwagandha in the ITP study Protandim resulted in 7% increase in median survival of male mice but there was no significant difference in survival at the age at 90% mortality the company selling pandum Life Vantage has gotten into some trouble with the FDA because of their misleading and illegal marketing claims that claim pandum can help with different conditions like cancer and diabetes there's no evidence that pendum or the specific ingredients in the supplement could help with those conditions the ITP study did find that pendum resulted in 7% increase in median lifespan but there was no difference at the end of life so in my opinion taking this supplement isn't worth it the problem is also that it's a patented proprietary blend which means that you don't know exactly how much of each ingredient is in the blend and it's also $66 for 30 capsules which is over $2 per day next up we have the most successful life extension molecule and the one with the greatest potential rapy it's been known to have life extension effects in animals for decades and in the it PP studies it has done so by 14% in females and 9% in males even if Romy was given late in life Romy increases median Survival by 10% in males and 18% in females and it attenuates age related decline in spontaneous activity in males but not in females in another 2016 study treating middle-aged mice with rap ayin for only 3 months extended their life expectancy by 60% and improved Health span that's very interesting because they treated the mice with rap ayine for only 3 months a mouse usually lives 12 to 18 months so they got repy in only about a quarter of their life and they still saw a large life extension effect for humans the equivalent duration would be something like 20 years which is a very long time but it's still not your entire lifespan but are there any longevity studies about rapamycin in humans if you don't know then rapamycin is used for organ transplantation rejection as it suppresses the immune system if taken chronically however there are now several clinical trials showing that rapamycin actually enhances immune system function when used transiently it appears that rather than using rapy daily you would have to pulse it something like once a week or once every two weeks to avoid the immunosuppressive effects and by doing that the elderly people actually see an improvement in their immune system function many longevity enthusiasts are taking Ramy off label in hopes of extending the lifespan a 2023 study by Matt caban and colleagues looked that 333 such people they found that at an average dose of 3 to 6 Mig per week rap a didn't have any adverse side effectss on health with the most common side effects being abdominal cramps and mouth Alters most people also didn't know if the drug was working but they did self-report improvements in their health brain function youthfulness coldness and general aches and pains the problem is that the placebo effect can be very big in these people who are taking rapamycin thinking that it's going to extend their Lipan you can't just buy rapamycin from the pharmacy you need to go out of your way to get it and if you are doing that then you probably have some expect that is going to improve your health so it wasn't a placebo controlled study overall I do think that out of all these compounds rapy is the most promising one I think it has the greatest potential of being the first geroprotective drug we obviously need a lot more clinical trials on humans to see what the effects are but many of the leading longevity experts do think that rapamycin does work in extending lifespan I'm personally not taking Romy at the moment I don't have any plans in the near future either I'm waiting for more of these clinical trials to come out in the next next few years the last compound is 17 Alpha estradi which is also called non-feminizing estrogen in the ITP study in increased media male lifespan by 19% and by 11% when fed late in life this is quite interesting and estrogens are known to have cardioprotective and neuroprotective effects it's even thought that estrogen might be one of the reasons why women live on average 5 to 10 years longer than men as you've seen repeatedly throughout this video most of the compounds extend lifespan in male mice more so than they do in female fale mice that's very interesting and it might be partly because of the six differences between male and female animals and in the ITP study 17 Alpha estrad didn't extend female lifespan what other Studies have also found is that the life extension effects of 17 Alpha estrad go away in castrated male mice which suggests that it works in the presence of elevated male hormones and androgens androgens and testosterone tend to shorten Lipan and they're associated with increased risk of heart disease which is why it looks like 17 Alpha estral counteracts those effects in males who have testicles it doesn't do so in females who don't have testicles and it doesn't do so in castrated males interestingly castrated males having also seen to live longer than regular males in different human cohort studies I'm pretty sure most men would like to keep their testicles and they would much rather take something like 17 Alpha estr rather than castrate themselves 17 Alpha estr is called non-feminizing estrogen because it doesn't have any of the feminizing effects of estrogen such as breast tissue growth or other feminizing effects it's obviously very early to say if 17 Alpha estral is going to extend lifespan or longevity in humans especially in male humans but I'll be interested to see the future clinical trials there you go these are the compounds that have been shown to extend Lipan in the ITP program they've tested many other popular molecules like reservatrol methylin blue nicotinum at riboside corcumin and MCT oil and those compounds didn't increase Lipan what's the Practical takeaway from this well personally me I'm going to macro do Glycine and I might think about using rapamycine in a few years but not right now if if you want to know about the non- phological evidence-based methods to slow down aging and add healthy years to your life then check out my new book the longevity leap in the description thanks for watching this video make sure to click a like And subscribe to future videos about living longer and staying healthier my name is seam stay optimized stay empowered