Genetic circuitry boosts cell longevity | Hacker News Reader

Genetic circuitry boosts cell longevity

science.org

68 pointsbirriel17 comments

A technical feat, strengthening the notion that ageing is not inevitable.

At the same time, I don’t think it is particularly controversial to say that if we start modifying our own genetics we could eliminate most diseases, including many aspects of ageing. The ‘problem’ if you like is that 1) there seems to be no ethical/careful way to do this that doesn’t amount to experimenting on children; 2) we will cease to be a homogeneous species. Intermediate solutions are post-germline genetic manipulation… but how feasible is it to gene edit a majority of adult neurons, for example?

The average child is born with about 60-70 mutations. A couple tweaks won't break up the species.

Do you have a citation for this?

That number seems within the same order of magnitude as I was expecting, but the fact that this has been quantified is fascinating.

Are there similar numbers for mutations per cell division or averages per year of life?

Rates of Spontaneous Mutation (Drake et al., 1998)[1] says that a human's genome accumulates around ~64 new mutations per generation through meiosis alone. Those mutations are propagated into every cell of the newborn baby. Over a lifespan, all cells in the body will mutate at a rate proportional to their division rate, leading to thousands upon thousands[2] of uncorrected mutations per individual, among the trillions which are ultimately corrected by DNA polymerase[3].

[1] https://doi.org/10.1093/genetics/148.4.1667

[2] https://doi.org/10.1038%2Fs41586-022-04618-z

[3] https://doi.org/10.1126/science.aaf9011

https://www.sanger.ac.uk/news_item/increased-mutations-in-ch... here's the most comprehensive article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/ also has some numbers

Note there's a selection bias here: any lethal mutation that causes a fetus to spontaneously die before a child is born is uncounted here. There are many tweaks that are fatal during development, you just don't count them if you only look at born children.

But is that selection bias relevant here? The tweaks we're comparing against are not lethal ones. The category is genetic spread among living humans, so mutations in living children should be the correct number to use as a baseline.

It's true that that selection bias exists, but so do a hundred other kinds of selection bias in earlier steps. As long we we're not looking at those steps, and any bias in them is already factored in to our number, we don't need to worry about those details.

It's not feasible to edit a majority of most adult cell types; it's not practical at this time. You'd need a very effective vector (high sensitivity and specificity). More likely, you'd want a vector that targeted neuronal stem cells and transform a large fraction of them. Those cells would then go on to make new, modified cells.

I do want to point out that were are absolutely very far from modifying germlines to eliminate most diseases. That's a common conceit, and as somebody who's worked in the field for 30 years: temper your expectations. A single person died in a single gene therapy trial 25 years ago and that pretty much stopped gene therapy in its tracks for a long time. Societal expectations for safety when modifying genes is far more stringent than any other medical technology.

Not to mention the socio-economic impact of who is chosen and who isn't. The movie Elysium comes to mind. That said, I think research on samples and growing tubes is fine. I hope for the day when we can just grow a new heart or lungs or pancreas for people who have cancer or something. Taken from their own "good" cells so there's no rejection.

"Not to mention the socio-economic impact of who is chosen and who isn't."

Yawn. The most boring and lazy complaint to this technology that I can imagine.

If we can edit, then in time there is no reason why the technology will not become affordable for the vast majority of the population.

Like insulin?

I think you might still run into rejection with that since its like not in sync with their immune system. So it would probably be better to temporarily have them on a pacemaker or mechanical heart while you grow a heart inside of them to replace the old one. Or the equivalent for other organs.

What does it mean to be "in sync" with an immune system?

AFAIK the immune systems works through antigen detection, the antigens that your immune system recognise as your own are innate to your own cells and are expressed automatically

Take that, “… in mice” people. This is in yeast!

In multicellular organisms, apoptosis actually promotes longevity.

Haha. Point taken.

To the second sentence though, you are referring to senolytics after the Hayflick limit of 50 cell divisions? Because after that cells secrete inflammation?

How does a cell secrete inflammation?

TLDR: Prompt:"Cellular aging in yeast (Saccharomyces cerevisiae) was shown to be controlled by a genetic circuit... On page 376 of this issue, Zhou et al. (3) reveal that introducing designed genetic circuitry to rewire these dynamics increased cellular longevity by 80%."

GPT: GMed Potato is able to last for 1yr in your fridge.

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