After 8+ months of taking rapamycin, I am sleeping better than I have for many years.
Only 3 months ago I had a rather large sleep stack. Now I only take melatonin and magnesium before I go to bed. I would take melatonin and magnesium before bedtime in any case. I did not feel the profound effect of rapamycin on me until after about 7 months, then it just continued to improve. My journey began with 5 mg/weekly and varied increased doses, sometimes overdosing, and finished with 10-15 grams biweekly with grapefruit juice. This was surprising to me as sleep improvement wasn’t one of the effects I expected.
Sorry, I just had to use this opportunity to sing the praises of melatonin.
As for melatonin, the heavy weight of evidence is it is a good thing.
It also has significant promise for certain kinds of cancer protection.
I have been supplementing with it for forty-plus years and it is on my essential list of supplements.
“The broad inhibitory effects of melatonin in breast cancer make it a promising agent and may add it to the list of potential drugs in treatment of this cancer.”
Melatonin supplementation has significant effects on triglycerides and total cholesterol levels, which was more evident in higher dose and longer duration and also in a higher concentration of cholesterol levels. Further studies are required to determine the benefits of melatonin on lipid profile."
I made a post awhile ago, but as long as you arent taking very high doses , then its okay.
heres what I said to someone saying they took 60-80mg of melatonin.
I would really caution against this practice , as you honestly are wasting melatonin and its completely unnecessary. Most melatonin people take are extremely higher than endogenous levels and really if you need it for insomnia or trouble falling asleep you should take no more than 1-5mg, maybe 10mg at the highest( and that’s pretty high too).
I have never seen any research in animals suggesting that spiking melatonin beyond natural peak levels results in any significant additional anti-aging benefit.
I think this article below does a good summary of some side effects of taking melatonin]
Our own melatonin plays an important role in regulating our sleep-wake cycle. Recent evidence raises questions about whether we should be taking extra doses to try to improve our sleep.
Considering melatonin supplements for sleep help? Learn about the science of melatonin and the benefits and risks of melatonin supplements.
Est. reading time: 8 minutes
I would just really caution against this. I currently am doing my PhD in mechanisms of sleep and circadian rhythms, and honestly think this is unnecessary if you are practicing good sleep hygiene and probably are giving yourself a unnecessary risk in relation to the “gain” of taking these high levels of melatonin. I think you would be better off focusing on other aging factors and just let your natural circadian rhythm do the job for you as long as you are practicing good sleep hygiene.
Well, yes, you can overdose on any supplement, but it doesn’t make it bad.
I am currently using 3mg nightly. And, at my last medical eye exam, I had no significant macular degeneration. Forty years of taking melatonin have seemed to have served me well.
P.S. Melatonin was the first anti-aging supplement that I heard of. Though no longer touted as an anti-aging supplement, it was back in the 90’s.
Another example of the 90’s melatonin proponents:
“Melatonin: Breakthrough Discoveries That Can Help You Combat Aging, Boost Your Immune System, Reduce Your Risk of Cancer and Heart Disease, Get a Better Night’s Sleep”
Let me add that I know melatonin as a hormone with multiple effects fairly well, as I did a lot of intense research on Alzheimer’s as my previous white whale. It is not a sleep hormone only. It controls a lot of other things like onset of puberty.
Intermittent supraphysiological levels may be unsafe in the long run as high levels of melatonin are associated with dementia, cognitive deficits, and early death.
Especially in the elderly it is related to orthostatic hypotension and falls which can result in death. It’s not even good for sleep quality if you examine publication bias very carefully.
Not to mention, high myopia can worsen and cause retinal detachment and vision loss. Dopamine and melatonin work together in the eye with opposing functions.
New info, though I don’t believe that telomere length is a limiting factor in people’s lifespan:
Results of a new analysis indicate that alcohol directly damages DNA, by shortening protective telomeres.
Telomeres are repetitive DNA sequences that cap the end of chromosomes, protecting them from damage. Telomere length is considered a potential biological marker of ageing, since 50-100 base pairs are lost each time a cell replicates. Critically short telomeres prevent cell division, and can even trigger cell death. Based on studies using leucocytes (immune system cells), shorter telomere lengths have been associated with several ageing-related diseases including Alzheimer’s disease, cancer, and coronary artery disease.
Research Paper:
Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects
What you’re referring to is a correlation, not yet causation thing. Could be true - and we have to consider the whole model (flawed as it is), the whole system, not just one part.
Let me throw a wrench on telomeres - we know people with a lot of stress have shorter telomeres and getting telomeres right (especially in cells that divide a lot) may become a limiting factor. And I recall there was an experiment with rats with more p53+telomerase activators with low rates of cancer and longer life span.
Unfortunately, I don’t have enough evidence to believe in a single aging clock, hence I don’t believe in limiting factors vs nonlimiting factors for a single clock. A unified theory is what I believe is why others are going towards that singular approach and I get why - CR overall is pretty robust and replicated (although in specific circumstances may be neutral or shortened lifespan). CR mimetics - although useful - as afaik are not quite the same. Not only that - CR makes little sense if you need to account for say acute wound healing (although pre-acute wound CR often makes sense). I also remember I felt horrible for a short period of time at 6% body fat with a “cut” (not even a large caloric deficit and I was not under malnutrition) - on top of possible lower immune function (that’s with optimal immunonutrition).
And we probably won’t understand close to the full aging process anytime soon (although Google’s other technologies mixed in with what they are doing at Calico has been inspiring enough to change my mind). A single “central” clock concept is very helpful for aging research too such that focusing on high safety profile type of interventions on the clock may be the low-hanging fruit solution - enough to buy us additional time.
My current thoughts are controlling telomere length is still important enough - particularly in specific circumstances (heart or cancer) - but subject to change.
I take half a gram to a gram of NAC before consuming alcohol, and about a gram of BHT the next morning. I followed this protocol for decades. It must be protective cuz my lab test all look pretty good and did even before rapamycin.
Thank you, sir, for your many excellent and informative posts. This is not one of those. The reaction to cannabis varies greatly from person to person. Just because a majority of people experience a pleasant high after THC consumption, does not mean that all others will. And just because you did not benefit from CBD does not mean that most others will have a similar result. On alcohol: you are a better man than me since you stopped drinking at 35; I am nearly your age and just stopped (at least for now) a mere 4 months ago.
And marijuana seems like it might age people faster:
Conclusions
These findings suggest cumulative and recent marijuana use are associated with age-related epigenetic changes that are related to lifespan. These observed associations may be modified by alcohol consumption. Given the increase in use and legalization, these findings provide novel insight on the effect of marijuana use on the aging process as captured through blood DNA methylation.
I drink alcohol a few times a week. I tend to start by also taking Dihydromyrecitin (0.5-1g) plus 1g of pantethine roughly every 3 pints of beer equivalent.
Pantethine is a non rate limited version of B5 which is a CoA precursor and accelerates the conversion of acetaldehyde into acetate. It is acetaldehyde which causes most of the damage from alcohol.
I wish I had known this earlier.
Pantehine can, however, cause bleeding to last longer and hence push up Bilirubin. Best not to take it too often. If you have problems with bleeding I would think avoid taking it.
Vitamin B5 itself might help, but I think the rate limiting makes it less effective.
One area that alcohol harms is blood cell generation so if you have a high MCV that may be alcohol related. Copper supplementation can, however, assist with that.
I think the best way to change your desire for alcohol is to find something to replace it. When I go out with friends, I tend to get the unlimited lemon iced tea or coffee (without sugar). I can put down enough of those to give myself a caffeine buzz that lasts all night. Especially the really good coffee…
There are supplements which are supposed to reduce the desire for Alcohol. I must admit I quite like getting drunk and if my biomarkers are not indicating a problem - I am inclined to continue using it from time to time. ALP last time was 58 IU/L (Weds 26/10/22) with the normal range being 40-150.
I have in fact seen that. Over my life I have been a heavy drinker for quite a few decades. In the mid 2010s for example I might drink 4 bottles of beer (approx 1.5l) and 1 bottle of wine almost all the nights of the week. That was obviously too much. Now I am tending to drink on maybe 2 days a week. Still relatively heavily.
In the end the question is what your body’s systems of repair can handle. That depends upon many factors. However, my data indicates that my health is now a lot better than 2020. That involves losing various medical problems such as obesity, angina and indigestion. On the other hand I am some distance from being tea total although I don’t drink most days of the week.
What do you think the key reasons for this are?
I see this in my parents, but I think its primarily due to increased disease/disability and loss of friendships & family who have had shorter lives. If you stay disability/disease free and your friends and loved ones also survived in similar condition, I wonder if the desire to live would decrease at all…
I think quality of life is part of it. I find my senses are more subtle now than they were a couple of years ago which means for example things taste nicer. I am also more flexible and can turn around in the car when driving and move from the drivers seat to the passenger seat easily - something I had problems with only two years ago.
