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Comment by cj | Hacker News Reader

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.

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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.

This only really holds for older people, who have basically no ability to recover lost muscle mass after a serious illness which makes it difficult them to continue to exercise.

The correlation is unambigous. The causation is a different story, e.g. illnesses often cause weight loss.

Which segments of these populations have high BMI because of muscle mass instead of excess body fat? Which segments have low BMI due to childhood malnourishment or current or chronic illness? These are just some of the very obvious questions that have already been used to relegate your conveniently concise "fact" to "interesting, but not instructive".

> 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.

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.

Is way too early to know about any downsides of these drugs. I’m afraid too many people are gonna find out the downsides when it’s too late.

These drugs have been around since 2005. Exenatide was approved by the FDA for use in 2005.

We've had plenty of time. Only their approval for weight loss is new

Exenatide was a very small population base. The approval for weight loss means this drug is being taken by millions of more people which leads to a larger sample size. The larger the sample size the more negative effects will be revealed. I’ll just leave this here for the future m. I have no evidence other than common sense that it is ridiculous to think that injecting a hormone randomly in your body does not lead to side effects.

Besides, who is going to be the one that links thyroid cancers and pancreatic cancers to these drugs? My father died of pancreatic cancer, no one really thought to ask why.

The majority is gaining literal years of healthy lifespan. It would take a lot of damage to even approach this gain for the average person. Like we used to do very invasive and impactful gastric surgery to try and get weight loss and nobody batted an eye, no?

> The majority is gaining literal years of healthy lifespan

You’re saying this like it’s true already. Let’s give it 10 years.

> You’re saying this like it’s true already

Because it is true already? You take an obese person who has a lower quality of life because of their obesity and give them a drug that helps them lose that weight and keep it if, they're literally gaining function and a higher quality of life from it. Today.

Phen-fen helped people lose weight.

Yeah, and? Fen-phen was a drug controversially approved in April 1996 and withdrew from market September 1997.

GLP-1s aren't remotely similar. Their approval was 20 years ago and have been in used by diabetics since.

I think for myself, regardless of what the downsides are - the likely alternative was death, which is still an option.

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.

Rapamycin modulates the immune system. I get that he's probably consulting a doctor but can you imagine taking this risk during a pandemic or even in older age? It makes me uncomfortable to play around with these very powerful drugs.

These roads people go down always arrive at eating collidal silver...

Get with the times, methylene blue is the new it girl.

As a party trick, it'll make people pee blue. But don't do this, it isn't safe. Especially without consent

The dosage for longevity is supposed to be low enough that this risk is minimized. Lots of things you do modulate your immune system (including e.g. exercise). It's a risk/reward thing, every time you get into your car you're also taking a longevity risk.

I think there are some proper human trials happening but the jury is still out.

> I think there are some proper human trials happening but the jury is still out.

That's exactly my point. No one really knows the risk that they are taking.

Surprisingly, many people seem to think that pushing a few random pills into a machine optimized over some million years of evolution will tune it so it works better. Go figure...

It works for the majority of modern medicine, so it's not all that black and white.

Yes, although even for modern medicine curative and preventative strategies are very distinct. Sure, they'll give you pills to compensate for a problem you already have. But there are few meds that protect you against stuff you'll maybe catch in the future. Vaccines and antibiotics are obvious examples, but I'm not aware of many others. The rest of preventative strategies overwhelmingly consists in correcting deficits or excesses (calories, vitamins, sleep, exercise etc.)

People are still getting nerve damage from too much vitamin B6 in energy drinks and vitamin supplements, and that's a well known and widely taken vitamin. The idea that you can take experimental drugs your entire life at little risk is optimistic.

I had no idea. At points in my life I consumed a lot of nutritional yeast.

How to hedge a bet 101:

1.you bet on risky stuff using something of value (money, health,...)

2.since you're unsure whether your bet will pay off, you bet some more on some other risky stuff, just to be sure.

BTW if you were wondering, of course all those proposed weird life-prolonging treatments are totally devoid of side-effects.

Oh there's plenty of people selling "side effect free" life extension supplements. But there's another name for side effect free medication: effect free.

Never put 100% of your savings into a single slot machine. Take 10% of your savings to 10 different casinos and distribute them to 10 slot machines in each, in order to hedge.

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.

Don't come and spoil our nice individualism with populational effects, you filthy rationalist !

What was the dose and frequency? I bet it was rather high. Or do you really think that 1 mg once per week will suppress the immune system?

And sleep

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