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Comment by bob1029 | Hacker News Reader

> 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 reversing aging. Your body engages in a process called autophagy when nutrient-sensing pathways are down-regulated. When you are stuffing your face constantly (i.e., every ~8 hours), there is less opportunity for this mechanism to do its job.

https://en.wikipedia.org/wiki/Autophagy

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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.

Autophagy research is all over the place and its hard to understand this stuff or make blanket statements, instead we just have to be flexible with it. Autophagy is always working and the ramp up happens pretty quickly for a lot of people. I think aiming for the 48-72 hour peak isn't helpful. Most people cant or wont fast that long. A lot of people on 16-18 hour daily fasts see benefits that suggest autophagy working well.

Also biology isnt computers, its not exact and all our bodies are very different. For example, say your standing autophagy rate is 3. 16-18 hours fasting its 7 out of 10. But at 48 hours its 10. The difference between 7 and 10 might not even be very meaningful on a practical health level. The difference between never getting to 7 because of "it takes 48 hours" thinking and never trying is then huge. Just a couple hours a day at level 7 autophagy or whatever could be life changing. I do about 14-16 hours a day and am happy I made that decision for myself. I do see benefits that are real seeming to me.

From what I've seen there's no real downside to 14-18 hour daily fasting and in theory incredible benefits. Its also worth mentioning for a lot of people just sleeping with an empty belly means a higher quality of sleep, so there's secondary benefits as well. Your gut 'taking a break' during those hours may also be another benefit in terms of gut health as well, but I'm more skeptical of that claim.

Personally I'd add 'consume and make tons of fermented food' to that list and also eat lots of prebiotics. Gut health is key to so many aspects of a healthy life - I have to imagine it helps with longevity (and lower stress). Nobody likes having stomach pain!

People love their probiotic pills but I'm not convinced - the amount of beneficial microbes is measured at bottling or production and who knows how many survive by the time they get to you. Not to mention how many survive into your gut once consumed.

Homemade sauerkraut or natto though? Pretty much guaranteed to be teeming with the stuff. And your grandparents and their parents were probably eating it their whole lives. It's a whole forgotten art / science that is thankfully making a comeback.

Anecdotally (obviously sample size of 1 so big grain of salt here) every person in my personal life who I saw live to a super long age and also maintain good mental fitness followed what you are saying above plus made their own fermented food into their elderly years.

At the worst it does nothing for longevity and you end up with more unique tasty food for yourself and your friends :-D

Probiotics fall into the same category as all other supplements: i.e. they can have some short term effects if your diet is really bad or you are recovering from GI disease, but there is not much evidence regarding general health improvement. And you also have the same issues as with all food supplements in that they are not FDA regulated or approved. So even if you think you actually need a particular dosage, you can't rely on what is written on the packaging. A balanced diet is a much better and healthier approach without any downsides.

I have personally reduced my a1c from 6.2 to 5.3, mostly by fasting for 36 hours per week.

I already cut refined sugar out of my diet several years ago.

> reduced my a1c

And therefore ?

Prediabetes is 5.7 to 6.4- this is a significant improvement.

All cause mortality or gtfo.

hopefully the OP is still alive, so we'll need to get back to you on that one.

Is exercise really a maybe?

Even stuff like "don't be overweight" is a maybe. This meta-analysis famously found that being overweight actually has a moderate protective effect: https://pmc.ncbi.nlm.nih.gov/articles/PMC4855514/

This is a BMI-only study and should be treated carefully. They also found a protective effect for one of the obese categories, which seems extremely weird (unless you consider bodybuilders or strength athletes, in which case it would be reasonable). If you replace "don't be overweight/obese" with "don't have excess amounts of fat" (in particular vascular fat) it is certainly not a maybe.

I feel like at the very least being overweight is harder on joints.

Also overweight is not obese.

> autophagy [...] usually takes at least 18 hours of continued fasting to even start

False. That would mean cellular debris would pile up unconstrained for pretty much everybody, which is clearly absurd.

> It is also an extreme cell response that is associated with high levels of cellular stress

Also false. It is a very essential cellular process. Read up on it, please.

You should read up on the literature. There isn't much, but this part is pretty well established.

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

This. Burning muscle also means losing tendon strength, which has downstream effects on your joints.

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

What do you mean by 'the early days' ? And how is it a life changer?

Early days as in the first ~4 months of the journey (which is lifelong…a formerly obese person will always be highly likely to regain the weight)

It’s a life changer because when you’re at a significant caloric deficit, your body sheds both fat and muscle. When you lose muscle, your metabolic rate drops, also lowering your rate of fat loss

If you lift even a little, your body will hang on to muscle more effectively, making it easier to lose and maintain weight over a longer period

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.

You can't meet your daily protein / caloric requirements in one meal. Also many vitamins / minerals compete for absorption so you don't want to consume all of them at the same meal either.

You are overstating the benefits of fasting. While it can be an effective weight loss strategy for some people, for those of us at a healthy weight there is no reliable evidence that it will improve lifespan compared to eating the same nutrients spread out across multiple meals.

I'm a large man and fairly active so I have to consume ~3000 kcal/day to maintain weight. If I try to eat that much in one meal it will make me physically sick. My digestive system just can't handle that much in one bolus.

Autophagy sounds like a great idea... if you completely ignore the Hayflick limit - non-cancerous human cells don't divine indefinitely!

> "human cells don't divine indefinitely!"

I apologize about the typo, but it's true that cells don't divine without a (Hayflick) limit due to telomere shortening. Excessive autophagy is detrimental. The best strategy is to prevent cells from becoming senescent.

No worries!

Not all cells divide (neurons and some muscle cells don't divide); some cells divide very slowly. And in some cases telomeres may be repaired but this increases the risk of cancer [0]

https://biologyinsights.com/what-is-telomere-repair-and-is-i...

I'm fully aware of cancer risks with substances such as astalagus extract, but maybe telomerase activators can be combined with anti-cancer strategies such as fasting, etc.

What I mean is that the Hayflick limit is a concept from the laboratory; it applies to cells that divide quickly, like skin cells, but it has limited practical use for strategies aimed at extending an animal's lifespan, because as the animal or human ages, it will lose neurons and muscle strength (including heart muscle).

In other words, 100% of humans relying only or mainly on telomere repair will be faced with Alzheimer’s, Parkinson’s, and/or ALS, as well as cardiovascular diseases, before they reach 100 years old.

I thought we're past the times when we thought cartilage, neurons, and other tissues cannot regenerate. Didn't we, for example, find that BDNF activators can trigger neurogenesis?

How do you create a well-connected motor neuron with a 3-foot or one-meter-long axon? Or brain neurons that are highly connected to other areas?

I would appreciate any pointers to a scientific article that describes this.

Peripheral neurons can regenerate [0]. Heart muscle also can repair through other factors [1].

[0]: https://pmc.ncbi.nlm.nih.gov/articles/PMC6336700/

[1]: https://www.sciencealert.com/new-study-reveals-more-about-ho...

Do you get acid reflux?

Simple solution: take an antacid, like Tums.

Which happily, is totally devoid of side effects.

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