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Review of Anti-Aging Drugs

scienceblog.com

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Re: Review of Anti-Aging Drugs

#41

Post by A_D_E_P_T »

pama wrote: post #15

Be careful when reading such blogs: > Note that the dosage in the mouse experiments is quite high — 0.1% of the body weight every day, meaning about 2 ounces a day for me (70 kg). Mouse and human metabolism are very different. A better starting estimate would be 5g/day, not 57g/day. I hope people dont accidentally overdose themselves because of lack of a pharmacology background.

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.

Re: Review of Anti-Aging Drugs

#42

Post by Aurornis »

pama wrote: post #15

Be careful when reading such blogs: > Note that the dosage in the mouse experiments is quite high — 0.1% of the body weight every day, meaning about 2 ounces a day for me (70 kg). Mouse and human metabolism are very different. A better starting estimate would be 5g/day, not 57g/day. I hope people dont accidentally overdose themselves because of lack of a pharmacology background.

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.

Re: Review of Anti-Aging Drugs

#43

Post by sigmoid10 »

bob1029 wrote: post #20

> Fast for short intervals regularly, and longer fasts as they feel good to you. You can effectively do this every day if you just eat once per day. When I was properly obese, this technique resulted in rapid weight loss. Zero exercise was required to see results, which was good at the time because the not eating part was about all I could handle. Being in a fasted state is as close as you can get to actually reversi…

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.

Re: Review of Anti-Aging Drugs

#44

Post by Aurornis »

starchild3001 wrote: post #39

This is a great discussion on longevity, though the main article focuses heavily on mouse studies. To add to that, I've been thinking about a framework that prioritizes the existing human evidence. My take, which I wrote about in the linked post, is to use a tiered approach: 1. Top Priority (Human RCTs): Start with what we know works in human randomized trials. This is our most solid ground and includes sustained wei…

> appropriate TRT for men with low T

You lost me here since this doesn’t appear in the linked article at all. You seem to be speaking about your own link, not the linked article on Hacker News.

Be especially careful with TRT advice on the internet or from local clinics that push TRT treatments. The definition of “low testosterone” used in the longevity studies is very different than the definition used by TRT clinics looking to grow their customer base.

There was an alarming study recently that showed a high percentage of men on TRT didn’t even have baseline testosterone bloodwork showing a deficiency. The clinics “diagnosed” them based on vague symptoms or questions, which is how they get around the fact that most men seeking TRT are not clinically deficient these days. Taking TRT will suppress natural production of testosterone and can lead to a lifetime need for TRT. Inappropriate dosing (which is common at the TRT clinics who want their customers to feel something early on) can also be net harmful and lead to cardiac complications or even psychiatric side effects like anxiety.

TRT should be a last resort for people with true clinical deficiencies after eliminating the typical contributing factors (alcohol, sleep, obesity, etc). It’s not appropriate to mix into a list of supplements to take because it’s on the short list of medicines that can make you permanently dependent by causing testicular atrophy. This isn’t a concern in patients who already have testicular damage leading to hypogonadism, but it should be a huge concern for the average guy walking into a TRT clinic because they heard it was going to give them an edge or help in the gym.

Re: Review of Anti-Aging Drugs

#45

Post by Aurornis »

cm2012 wrote: post #24
cj wrote: post #2

From the conclusion paragraph: > Your primary life extension program is diet and exercise. Choose a diet that works for you. Stay slim. Considering heart disease is the #1 killer, doing whatever you can to not die from heart disease is the best place for most people to start. Even in 2025, diet and exercise are still king.

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.

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

This doesn’t mean being slightly overweight from age 20 through 60 is an advantage.

Re: Review of Anti-Aging Drugs

#47

Post by Aurornis »

These articles really need a lot of context to parse as they paint some of the compounds as having potential upside without downsides.

Metformin is amazing in people with diabetes, but among non-diabetics taking it for vague life extension claims it’s often discontinued due to side effects.

Rapamycin has fallen out of favor among many in this space because they felt it was producing net negative effects as well as causing very annoying side effects like blisters in the mouth.

I’ve followed supplement and fitness forums for years. It’s amazing how frequently a prescription medication will be held up as a wonder drug, but then people who try it discover it isn’t helping them or is even causing other problems they didn’t think about.

EDIT: There are some serious scientific errors in this blog (dose conversions from mice studies). After clicking around the author appears to be into some quackery and conspiracy theory stuff as well. I flagged this submission because it’s not as scientific of a source as it claims.

Re: Review of Anti-Aging Drugs

#48

Post by nutribueno »

Aurornis wrote: post #47

These articles really need a lot of context to parse as they paint some of the compounds as having potential upside without downsides. Metformin is amazing in people with diabetes, but among non-diabetics taking it for vague life extension claims it’s often discontinued due to side effects. Rapamycin has fallen out of favor among many in this space because they felt it was producing net negative effects as well as ca…

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.

Re: Review of Anti-Aging Drugs

#49

Post by obloid »

adamgordonbell wrote: post #3
cj wrote: post #2

From the conclusion paragraph: > Your primary life extension program is diet and exercise. Choose a diet that works for you. Stay slim. Considering heart disease is the #1 killer, doing whatever you can to not die from heart disease is the best place for most people to start. Even in 2025, diet and exercise are still king.

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.

I recently saw a patient with overwhelming MRSA sepsis with multiple foci of infection including epidural abscess (around the spinal cord), and meningitis. This person was taking rapamycin presumably for "life extension" purposes. Almost certainly the immunosuppression from the rapamycin made the infection much worse.

I'd be very wary of taking an immunosuppressive drug as an otherwise healthy person for theoretical life extension properties.

Re: Review of Anti-Aging Drugs

#50

Post by hn_throwaway_99 »

I thought this was an informative post, but for many of these compounds the simple "life extension" metric is the one that is least interesting to me.

I have no problem dying in my 80s or 90s, but I just want to ensure that as much as possible that I have a solid mind and body right up until I die. For example, my father has been taking metformin for nearly 30 years after surviving a heart attack in his 50s (he has type 2 diabetes). He's now in his mid 80s and has basically no significant cognitive decline, despite that his father and both of his brothers had severe dementia when they died. Obviously this is just one anecdote and I'm not arguing anything about the specifics of metformin, I'm just saying that the fact he is able to enjoy such an active life in his 80s is the biggest gift - if he died tomorrow I think he and all of his family would just be so grateful at the vibrant life he had.

Heck, for me I'd be fine with a drug that slightly reduced my lifespan if it gave me better quality of life up until the end.

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