Review of Anti-Aging Drugs

Taurine and Vitamin E are readily available and seem prudent.

For melatonin, tryptophan plus niacin would maximize the serotonin pathway (note this is dangerous when used with SSRIs).

How many of these are easily available? I had no idea that royal jelly is sold as a supplement.

If we really manage to crack the code on aging, How certain are we that it's merely something to be delayed? Apparent age is at least somewhat reversible via lifestyle factors e.g. diet/exercise/sobriety.

While autophagy does correlate with fasting and some studies link it to health markers, it should be noted that it usually takes at least 18 hours of continued fasting to even start and only goes into full swing after 48 to 72 hours. It is also an extreme cell response that is associated with high levels of cellular stress, which might have understudied long term detrimental effects. A simple calorie reduction either by eating fewer highly processed meals or regular intense exercise is much more universally accepted as longevity boosting, because it combats overweight, which is by far the most common disease that shortens general lifespan in the western world. There's really no good reason to force your body through these extreme diets. Don't be overweight, don't smoke, don't drink alcohol, maybe go easy on junk food and maybe do some exercise. And get your regular medical check-ups. Then you're already at the pinnacle of clinical longevity science. There is no actual anti aging drug yet that has a proven effect on humans. Best we have are some moderately promising monkey and small mammal studies, but they generally don't translate well.

Latest research (as in only ~2m old) dispels that narrative a bit but not entirely. Looks like spermidine is the autophagy signal but they’re not sure fasting does t always increase spermidine

Also…lifting light weights for like 10 minutes a day at home is a lifechanger in the early days

Fasting without any exercise has a hidden downside: you’re not just burning fat, you’re also burning muscle. Less muscle → lower glucose disposal capacity → systemic insulin resistance. The problem is that insulin resistance doesn’t stop in muscle — the brain is highly insulin-sensitive, and once central insulin signaling gets disrupted you start seeing network-level dysfunction and cognitive impairment (there’s a reason Alzheimer’s is sometimes called “type 3 diabetes”).

So yeah, autophagy is real, but pairing fasting with at least some resistance work is critical if you don’t want the “anti-aging hack” to backfire by accelerating muscle loss and brain decline.

See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462531/ for brain insulin effect

Associating weight loss with the healthiness of oneself is a mistake.

One can subsist on Oreos at a "healthy" weight if they consume <2,000 calories worth of cookies per day. They will not be a healthy person.

Do you get acid reflux?

I mean this guy is not a scientist. He's an enthusiasts aping scientific process. Look at how he talks about the "10-20% flexibility". Hypothesis assumed true, no supporting evidence. Same with his idea of being young longer. No evidence supports this, yet his comments proceed as if it's a gospel truth

In the absence of actually lengthening the telomeres, everything falls short in the anti-aging department.

Most lifestyle habits contribute to shorting the telomeres as little as possible, which guarantees good health no matter the age, but still aging, albeit slower.

Given the current technology trajectory, many people including me, think that we are very close to totally stopping aging, and even reversing it.

> don’t smoke, keep your weight down, move often, sleep properly, keep blood pressure and cholesterol in check, and go easy on the booze.

And UVs, don't forget UVs.

GLP-1s are the first hint of that.

This is just another way of saying there have been no big advances in clinical anti-ageing. And that's probably because little serious effort is going into it, compared with say, military spending.

What side effects cause people taking Metformin to discontinue it? I'm taking, but haven't noticed any, but... you don't notice your baseline, I suppose!

I'm surprised at the lack of intersectional shitposting when it comes to this subject, something along the lines of "FAANG intern tech bros making $1.5m TC are microdosing on ivermectin for health benefits." Get Wired or some other shit rag (the Altnatic?) to run with it complete with fancy full-viewport animations and gushing narrative intro over how it all started when someone's pitbull decided to take a shit in jeff bezos office.

Scaling mouse doses to human by body weight is a common rookie mistake.

A better estimate for dose scaling uses body surface area. Even with that, inter-species differences don’t allow prevent extrapolation.

Scaling by body weight leads to the common mistake of dismissing mouse studies because the casual observer does the match (by weight) and thinks the dose used was excessive.

It’s such a basic topic in medicine and scientific research that I don’t trust anyone who scales by body weight.

lol, that one was really a howler.

You're spot on. But for the rest of the forum:

The most commonly accepted mouse-to-human conversion is: (D)*(3/37) = H

Where D = the mouse dose in mg/kg. H = human dose in mg/kg.

So if a 25g mouse eats 0.1% of its bodyweight in taurine, that comes out to 1000mg/kg. It translates to 81mg/kg for a human. If you weigh 100kg, an equivalent daily dose for you is 8.1 grams/day.

The rat equation is similar, but 6/37 rather than 3/37.

Lack of pharmacology background doesn't seem like the biggest issue when extrapolating from mouse to human.

I just learned this the other day, but its called allometric scaling. Definitely far off linear.

> Be careful when reading such blogs

I followed a link to another blog post of theirs in which they go on a rant claiming there was a conspiracy to suppress chloroquine and ivermectin as COVID treatments. I dont think anyone should be taking health advice from this person

Your overall mortality is actually best when you are overweight but not obese.

Life expectancy at overweight bmi > standard bmi > obese bmi > underweight bmi.

A few extra pounds when you are older helps you survive illness.

The data is really really clear and replicated on this.

And if diet alone isn't getting you to a healthy weight, the GLP-1 drugs are miraculously effective and don't have a lot of downsides aside from cost.

Also this:

> The best reason to take multiple life extension supplements is to hedge our bets, because we really don’t know which of them are effective in humans.

And earlier:

> Personally, I take large doses of rapamycin 2 days a week, 8 weeks per year. For personalized recommendations, you can consult your favorite life extension doc.

And sleep

Diet and exercise are well know for the effect you're looking for. Its just not easy

The text says yes. Also the text says other studies supposedly shown decrease in lifespan in humans: "but the conclusion of this study was that supplementation with vitamin C depressed lifespan, probably by inhibiting production of the body’s native antioxidants, including glutathione and SOD=superoxide dismutase."

If 100 year olds were truly healthy, then I strongly suspect we'd see a shift in societal structure and expectations for retirement. Societies tolerances for a permanent upper class of retirees and a permanent lower class of workers would likely not last - worker's would likely be unwilling to do the same job for a century.

Realistically you can maybe get another couple year from what I can tell. Is it worth it?

I'd focus more on qulalitiy of your life. not everyone will die of something all these can help with, the obese person I used to know enjoyed eating - and we can now say in hindsight that diet changes would not have helped him live longer.