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New universe of miniproteins is upending cell biology and genetics

sciencemag.org

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Re: New universe of miniproteins is upending cell biology and genetics

#101
post #49

Earlier quoted context omitted.

I recommend reading "Being Mortal" by Atul Gawande to get a good sense of how hopeless "curing aging" is. Although that's not the focus of the book it does a wonderful job describing the challenge. The way it reads to me as a lay person, the body just falls apart. Things go wrong. It's not one thing going wrong, it's a very long list of disparate problems that ultimately aren't survivable. Aging isn't a losing battle…

I never read the book, but during the last couple years I became more attentive to things in life. Nothing special, but just the general flow of life so to speak. I started noticing an interesting pattern. There is pretty much always exists a single solution to any problem. A core solution. A polymorphism in programming could be an example of what I mean. Say you have a program with a bunch of similar entities and a…

The human genome is full of harmful mutations. While many are widespread and some are shared by everyone, we each still have our own unique collection of them. I often wonder how much longer we'd live with every obviously harmful mutation reverted.

Re: New universe of miniproteins is upending cell biology and genetics

#102
post #83
post #7

Earlier quoted context omitted.

This is why you should be very skeptical of anyone who claims transparency between genetics and complex phenotypes.

Which is why I have zero interest in things like 23 and me. I worked in a genetics lab and the longer I worked there, the more I realized how little we understand.

Sure, we don't understand much detail but we know a whole lot of things like "you're x% more likely to get y disease", and if y is something that can be monitored or tested for, this can literally save your life.

BRCA and heart disease come to mind.

Re: New universe of miniproteins is upending cell biology and genetics

#103
post #77

""" Later in life, myoregulin steps in to help regulate muscle activity. When a muscle receives a stimulus, cellular storage depots spill calcium, triggering the fibers to contract and generate force. An ion pump called SERCA then starts to return the calcium to storage, allowing the muscle fibers to relax. Myoregulin binds to and inhibits SERCA, Olson's team found. The effect limits how often a mouse's muscles can c…

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Re: New universe of miniproteins is upending cell biology and genetics

#104
post #73
post #40

Earlier quoted context omitted.

Wow. I understand that you are a layperson, but that’s a very strong statement in my view. What do you base it on? Or did you just pull it ”out of a hat”?

First, the goal I'm shooting for is the conquest of aging, effective biological immortality, not just living 150-200 years. When understanding a complicated existing system, like a program, with the intention of making changes to it or fixing it, I find there are characteristic phases to it. There's the part where you have no handle on it at all. At this point you think there maybe isn't that much to the system. Then…

Just to your first sentence: even if we had biological immortality, the current estimate is that you can only make it about 250 years before on average you suffer a fatal accident.

Beating aging isn't really enough - we have to beat death.

Re: New universe of miniproteins is upending cell biology and genetics

#106

Earlier quoted context omitted.

This is "the andy grove fallacy": it's not clear that you actually can , because code and computational hardware was designed by humans and biology emphatically was not. http://blogs.sciencemag.org/pipeline/archives/2007/11/06/and...

I'm starting to wonder if there are physical limits to cognition and if we've already hit them. Maybe it's impossible for the physical universe to understand its own complexity.

We've hit them long ago. We're now using massive parallelization to go forward.

Re: New universe of miniproteins is upending cell biology and genetics

#107

Earlier quoted context omitted.

i've been doing biological/biomedical research for about 20 years now (god, that's a scary thought...) I don't think that biology is well modeled by "being a meat computer", in general, but as far as the analogy goes ... : What we are debugging is 4.5 billion years of grad student code in at least a few dozen languages, with no documentation, method names that are outright lies, no separation of concerns at all, the…

I...doubt that's an accurate characterization, because the things that you are describing lead to fragile software. Biological systems are hard to understand and to modify, but maybe that's more due to redundancy that has evolved than to systems that are coupled like bad software systems. After all, if they broke like buggy software, we wouldn't have so many diseases to study; living things would just crash and stop.

It's extremely fragile, couple molecules of bad input and the whole thing comes crashing down!

Re: New universe of miniproteins is upending cell biology and genetics

#108
post #84

Earlier quoted context omitted.

Indeed. The whole "One Gene, One Protein [One Phenotype]" [1] dogma went out quite some time ago. ... But people and genetic testing companies seem to want to keep it going. [1] - https://embryo.asu.edu/pages/george-w-beadles-one-gene-one-e...

> But people and genetic testing companies seem to want to keep it going. You can still get alot of mileage out of a simplified, inaccurate model. If you just say to yourself, "well, this whole gene thing is hopelessly complex", then you'll never get anywhere outside of a lab or personal project. Applied biology especially, and medicine in particular, seems to require grossly simplifying assumptions in order to make…

You are basically saying "lying to people can make you some money". Indeed…

Re: New universe of miniproteins is upending cell biology and genetics

#109

Earlier quoted context omitted.

i've been doing biological/biomedical research for about 20 years now (god, that's a scary thought...) I don't think that biology is well modeled by "being a meat computer", in general, but as far as the analogy goes ... : What we are debugging is 4.5 billion years of grad student code in at least a few dozen languages, with no documentation, method names that are outright lies, no separation of concerns at all, the…

I...doubt that's an accurate characterization, because the things that you are describing lead to fragile software. Biological systems are hard to understand and to modify, but maybe that's more due to redundancy that has evolved than to systems that are coupled like bad software systems. After all, if they broke like buggy software, we wouldn't have so many diseases to study; living things would just crash and stop.

Do not doubt experts on this field. What he's saying is true.

> Biological systems are hard to understand and to modify, but maybe that's more due to redundancy that has evolved than to systems that are coupled like bad software systems.

No, it's not. It's all highly interconnected. There are no nice decoupled modules. If someone is showing you a module from biology which seems to have no interactions, he's leaving out information.

The only reason biological systems are not as fragile (although they also are. E.S. Collizi did some interesting research on why) as you think is precisely because they are so interconnected and redundant.

Furthermore, you seem to misunderstand why we don't see fragility. It's not because we get sick instead, but because nearly all of the nontrivial mutations are highly lethal, and the fetus dies in utero and you get a miscarriage. Most miscarriages happen so early the mother doesn't even notice.

Re: New universe of miniproteins is upending cell biology and genetics

#110
post #91
post #24

Earlier quoted context omitted.

I think the real challenge is mind boggling complexity of interactions. Suggesting it’s a question of funding etc is vastly understating the actual issues. Curing cancer for example is a vastly simpler problem.

Not only simpler, curing cancer is also necessary for curing aging.

Absolutely. There is already a great deal of work on the metabolic side, such as removing biofilms of cancer with AGE (aged garlic extract), slowing or stopping metastases with bio-availability enhanced Curcumin, up-regulating autophagy and cell apoptosis with the up-regulation of NRF2 via cycling Sulforaphane and Myrosinase, starving cancer cells by removing all glucose and processed carbs via Keto and intermittent fasting, 5 day FMD (fast mimicking diet). All of these things highly complement Chemo, increasing the effectiveness and mitigating much of the damage caused by Chemo Therapy.

On the repair pillar, quite a bit of work is being done with CRISPR to attack cancer cells. There is also research on targeting specific cells using sound (11th harmonics) and destroying them.

Sorry I don't have any links to share. I must get back to work. :-)

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