Comment by felipemnoa | Hacker News Reader

Comment by felipemnoa | Hacker News Reader

The part that really called my attention is this one:

>>Cells pick up damage all the time, either through environmental exposures or simply as a byproduct of their normal metabolism. If the damage is sufficiently critical, the cell will respond by committing an orderly sort of suicide called apoptosis, which keeps it from causing any further problems. For lesser damage, there's a less drastic alternative called senescence, in which the cell remains active and contributes its normal functions to the organism's health, but it commits to no longer dividing.<<

Old people, lots of senescence cells no longer dividing, young people, lots of young cells still dividing. Aging kind of makes sense when looked at it this way. As long as cells are able to keep dividing you may be able to stay relatively young.

Knowing nothing else it seems that you must keep the number of senescence cells low to keep the effects of aging at bay. Of course, it is probably much more complicated than this. At a minimum this may be a piece of the puzzle to figure out long life.

The key aging problem is that DNA damage is accumulating over the lifetime. Some cells reach apoptosis, some reach senescence, some reach cancer, some keep on being normal for a while.

Culling senescent cells does not undo the accumulated damage. You are making room both for cancerous and normal cells. Normal cells are still damaged though. I'm guessing the net contribution is still positive, but the specter of cancer is still looming.

On the bright side, I hope that cancer can be managed purely mechanically. Imagine dropping by for your weekly ultra-targeted radiation therapy to kill this week's tumors before going for lunch.

Silly question: how difficult would it be to extract your DNA code into digital format and then create cells based on that digital formatted DNA and put them into your body?

Note: not at all a biologist as you can probably see from the way I phrase things :)

I'd rather have my cells replaced with transistors - one by one. That way I might have a chance to outlive that radio made in 1960...

I imagine it'd be far easier to just extract existing stem cells from the body, freeze them, and then every once in a while wake them up, culture some, and re-seed the body with them.

> Imagine dropping by for your weekly ultra-targeted radiation therapy to kill this week's tumors before going for lunch.

I suspect if we ever reach such a distant future, we'll consider most radiation therapy to be a very blunt and barbaric instrument (even if ultra-targeted) and use some kind of nanotechnology instead. Some engineered virus or bacterium or nanomachine that hunts down the carcinogenic cells.

Do you have a source on the claim, that accumulated DNA damage is key? As far as I know, DNA damage happens all the time, is usually no threat at youth, and the real problem is rather the ever increasing inability to repair, or kill defective cells with age. (Getting a tan comes from the signaling of DNA damage, so cells are well prepared for this, to some extent) This is were senescence becomes very important. It's not the senescent cells themselves that become cancerous, but other dysfunctional cells which can flourish in a "fog" brought on by senescence signaling havoc and intracellular trash, obstructing internal and external kill commands. The weakening immune system is part of this too. There are other parts which become cancerous just by chance, like the endless recombinations in antibody creation will ultimately result in rogue lymphocytes. But usually cells can detect damage and repair it, kill themselves when unable to, or get killed when misbehaving.

There’s this https://en.m.wikipedia.org/wiki/DNA_damage_theory_of_aging

Damage happens all the time, and unrepaired damage accumulated over the lifetime, hence aging.

You have an interesting point with prevalence of senescent cells can interfere with natural immune response to cancer.

Thanks. I think we meant the same, and it's rather a question where your argumentation's starting point is set, because Wikipedia concurs, that DNA damage is caused by decreasing repair or apoptosis.

Anyway, I think this is where some lifestyle fads can become interesting. Sure, there are definitely some aspects to aging that are unaffected by this, but I think better chances of reaching current max human age are in our hands somewhat. Balancing IGF1 and frequently giving the body a break to repair, kill, and remove trash, are sound targets IMHO. So for me that is: restriction of certein makros, in particular animal proteins and refined carbs, early and midlife to lower IGF1 (raising it seems beneficial in old people); short term fasting every now and then. Both have shown to increase apoptosis and repair. It's not even hard to do, if you stick to a blue zone typical diet (plantbased diets are associated with double digit reduction in overall cancer risk, which is huge considering lifetime death by cancer risk is 1/5) and have a daily fasting window of 13+ h (eg. Shown to reduce reoccurrence of breast cancer). I focused on cancer here, because intuitively it seems like a good marker for DNA maintenance.

"plantbased diets are associated with double digit reduction"

How about a source.

Can you imagine if one of the cures to aging is safely removing senescent cells from the body? I'm not going to say its easy by any means, but it does seem straightforward in an unexpected way ("right under our noses"). Very exciting times in biomedical research. My hope is that anti-aging quickly accelerates into an industry instead of basic research (requiring checks, balances, all that jazz to keep the snake oil salesman and quacks at bay), which should allow for orders of magnitude of funding to flow into finding protocols for treatment (from an aging populace).

Eagerly awaiting reasonattlm's take on this.

>>Can you imagine if one of the cures to aging is safely removing senescent cells from the body?

At a minimum it seems that we are on the right track. Pretty exciting times.

You have to be careful not to cause cancer in the process.

From what I read, a lot of the things the body does, which have aging as a side effect, are intended to block cells from becoming cancerous.

For example a senescent cell - it might be damaged, and if it dived it might become a cancer, so better stop it from dividing. But we still need it, so don't kill it off.

Now you might think - actually, let's kill it and let some other cell divide and replace it. But that creates more cell division, which are more opportunities for cancer.

Basically, it's a delicate balance.

I suspect a different balance is also possible (there are animals without cancer for example), but the hard part is you must change all the parts at once (into the new balance), and simply stopping one part of the process will cause cancer.

This is going to make the research very hand without truly understanding all the moving parts, and joining all the different treatments into a single working whole.

What's needed is a fast-living animal, that ages, and gets cancer, in the same way humans do. Then you can just experiment without understanding.

> What's needed is a fast-living animal, that ages, and gets cancer, in the same way humans do. Then you can just experiment without understanding.

A simulated human?

Sadly, no. Cells are very complex. Whole multicellular organisms are even more complex. We don't have models nearly good enough to replace laboratory experiments with E. coli, much less good enough to replace medical trials with humans.

Do we need to understand anything about how a multicellular organism works, if we have 1. a working model of biology on the intracellular level, and 2. a working model of stereochemistry outside the cell, and use these to just "play out" cell division from an initial gamete within a simulated womb?

(I know that's A Lot of computing power, but maybe an algorithm like HashLife could make this possible by, say, 2100?)

If it's possible to do something like this at all, I think it must be based on techniques largely yet-to-be-discovered. To accurately model biology on the intracellular level, you need a "map" of the cell down to the molecular level, plus fast, general, highly accurate methods for simulating molecular-level chemistry.

For the chemical simulation side of things, it would take many centuries of continued Moore's Law progress to make today's most accurate algorithms for fully quantum chemistry run fast enough. And the wild ride of Moore's Law already appears to be closer to its end than its beginning. We'd need fundamental algorithmic breakthroughs to make it feasible without relying on better simulation hardware solving the problem. That might be possible, but I don't when/how/if such algorithms may appear.

On the problem of getting a ground-truth molecular map of a cell in the first place, we know that there are many gaps in current models. We're not sure where all of them are. Even if you had the fast, efficient, vast molecular simulation capacity I sketched above, it would still take a lot of experiment/simulation comparisons to be sure that all the biologically relevant features had been captured in the original model.

Even now I'm probably badly understating all the problems on the biology side. I worked at the interface of chemistry, biology, and chemical physics, but I was more familiar with the software/physics side of things. I learned just about enough biology to be useful in my role and to be grateful that even my most complicated debugging sessions didn't involve 3 billion years' worth of undocumented legacy code running on wet nanotechnology.

I'm pretty sure that we're very far from that. We can't even simulate relatively simple processes in timely manner.

And all the much-heralded advances in AI still produce email notifications that are kind of like those old Ad-lib games where the blanks get filled in by gobbledygook.

And after listening to one sleep-inducing waterfall video for a single long night of sleeping the next day about 2/3 of my Youtube homepage's suggestions are about soothing, meditative, nature videos... what a laugh.

> Can you imagine if one of the cures to aging is safely removing senescent cells from the body?

Very rarely are things in biology so simple. Everytime we thought something was useless in the past (junk DNA, appendix, tonsils, ...) it turned out that removing it causes damage somewhere else.

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