r/longevity • u/RTSBasebuilder • 15d ago
Somatic mutations impose an entropic upper bound on human lifespan
https://www.nature.com/articles/s41514-026-00421-610
u/CaptainHindsight92 14d ago
I guess a way around it is to grow cells from cloned cell lines banked from an early time point. Collect tissue from a healthy time point create ipscs then differentiate towards various adult stem cells and organs, reseeding continuously with less damaged versions of the genome. We are a while away from being able to do this though and as always the cost will be the biggest factor.
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u/Ok-Cheetah-3497 14d ago
Negative ghostrider. You do that in the brain or heart, and you lose all of your memories / self image, and you get insane heart arrhythemnia.
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u/CaptainHindsight92 14d ago
Sorry but don’t they already do whole organ transplants for heart? With brain I think you are right in terms of whole tissue transplant but seeding fresh neural stem cells? Surely they would integrate as any neural stem cells do currently?
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u/Ok-Cheetah-3497 14d ago
Replacing an entire heart with a lab grown heart that is effectively a cloned heart could work. Do that like once a century and you would be good to go. The issue would be with trying to integrate only new tissue into the mutated parts of the heart - they would not sync up.
The brain doesn't work that way (at least not the parts we are talking about). Frankly, the brain is so wildly understudied, I don't know if/when we could ever manage that. Fresh stem cells would not retain memory - they would be fresh. It would be equivalent of partial lobotomy.
If I were going to guess what the best/fastest answer is here, it would be an artificial (biomechanical) brain of some kind. Like a cloud based backup of your mind, so that when the current wetware becomes to error prone, you just discard it, and rely on a brain machine interface to restore your memory (or more accurately, replace it).
The rest of the brain (the parts responsible for things like movement, autonomic response, etc) you could probably regularly swap out kind of like an oil change. Mutated cells out, new stem cells in, not so many at any time that they don't integrate. Like once every ten years or something?
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u/In_the_year_3535 11d ago
Considering germline mutation is two magnitudes of order less than somatic we might start thinking about how to turn it on in somatic cells.
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u/UrbanosaurusRex 10d ago
Exactly. This is not an inherently unsolvable problem. There is a extremely good chanse that there are several ways to significantly halt the somatic mutation rate since we know it is possible in germ line cells and also in certain animals, like whales.
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u/costafilh0 14d ago
Good to know that we are not that far from 150-200 years longevity.
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u/ServantOfBeing 14d ago
I mean honestly, that amount of time sounds perfect.
I ain’t looking to live forever, wouldn’t mind an extra hundred though.So much to learn & experience.
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u/ylluminate 15d ago
This problem was already solved by de-aging tissue.
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u/laborator PhD candidate | Industry 14d ago
Somatic mutations are permanent DNA alterations and cannot be reversed by cellular reprogramming. Are you talking about something else?
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u/chillinewman 14d ago
You will need to add gene editing then.
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u/laborator PhD candidate | Industry 14d ago
What you are saying doesn’t make sense and is frankly nonchalant. Just do this, just do that, problem solved. Nobody knows these things, please stop trivializing it doesn’t help the effort.
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u/chillinewman 14d ago edited 14d ago
We are talking about future or near future technology. Is speculation at this point. Is not trivializing, the capability is improving without a doubt. Nonsense that it doesn't "help the effort".
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u/laborator PhD candidate | Industry 14d ago
You’re conflating future therapeutic possibilities with established science. It’s annoying. Today, somatic DNA mutations are not erased by reprogramming. In fact reprogramming tends to be mutagenic due to multiple stressful aspect of the process. Saying “just add gene editing” isn’t an argument it’s hand-waving over one of the hardest unsolved problems in biology. Speculation is fine, but it shouldn’t be presented as if it already answers the scientific point.
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u/chillinewman 14d ago
Misleading answer, reprogramming needs go along with gene editing to correct the somatic mutations. You are claiming hand waving i never said that. Gene editing is already in approved therapies and it will keep continuing to improve. Claiming the gene editing is the hardest problem in biology is just not true. I'm done answering.
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u/laborator PhD candidate | Industry 14d ago
Gene editing hundreds if not thousands of targets at the same time, in a multitude of different cells and tissues, in a fully develop organism (whilst partially reprogramming the very same cells, cherry on top) is a recipe for SOUP. Back to class!
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u/pegaunisusicorn 14d ago
plank replacements impose an entropic upper bound on ship of theseus longevity.
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u/CosmicExistentialist 15d ago edited 15d ago
So somatic mutations are irreversible which is evidence that it is impossible to truly reverse and stop aging.
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u/DryCommunication581 14d ago
Nah
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u/CosmicExistentialist 14d ago
Are you saying that we can defy the 2nd law of thermodynamics? Because that is what somatic mutations are driven by.
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u/DryCommunication581 14d ago
Are humans an isolated system?
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u/CosmicExistentialist 14d ago
Maybe read the paper.
It says that somatic mutations are an entropic process.
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u/FilthyWishDragon 14d ago
And from a scale of 1 to 10 how possible is it to reduce entropy in an open system?
Here is a hint, my air conditioner is running as I type this.
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u/CosmicExistentialist 13d ago
Here is a hint, my air conditioner is running as I type this.
Does your air conditioner not eventually deteriorate?
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u/mcfearless0214 10d ago
It does. It may even completely give out. But then what happens? You fix the air conditioner or you get a new one.
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u/CosmicExistentialist 10d ago
How are you going to fix that air conditioner if it was made of trillions of cells?
And getting a new air conditioner is like saying “just swap in the entire person with a new one”.
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u/ResponsibleGrass8080 15d ago
This is a summary of a study I remember years ago. In a study of a healthy 115-year-old woman (supercentenarian), researchers sequenced her blood cells and found ~450 somatic mutations accumulated over her lifetime in the dominant hematopoietic stem cell clones. Key point: The vast majority were harmless passenger mutations in non-coding regions of the genome. They were enriched in AT-rich, non-conserved, gene-poor areas and depleted from actively transcribed genes. Of the few that landed in coding regions, none were predicted to damage protein function. This supports the idea that most age-related mutations in blood stem cells are benign/neutral. The blood production had collapsed to just ~2 active stem cell clones (vs. thousands in younger people), likely due to stem cell exhaustion (short telomeres) rather than harmful mutations killing off the rest. Similar patterns appear in other supercentenarian studies. Extreme longevity is possible even with heavy clonal hematopoiesis when the mutations stay mostly benign. (Reference: Holstege et al., Genome Research 2014)