Turning back the clock: Human skin cells de-aged by 30 years in trial
news.sky.com
news.sky.com
In short, we're still far away from using it in humans (10+ years). Currently, all companies working on this are in pre-clinical stage, with turn.bio as the closest, expecting to go into clinical trials late this year.
This tech is exciting but there are still a lot of limitations:
- Risk of cancer: this technology is based on the work of Yamanaka in 2006, who discovered 4 factors that can turn any cells into pluripotent stem cells. The work in the OP article basically used the same 4 factors, but only partially, so that the cells became "younger" without losing their identities (i.e. turning into stem cells). This requires understanding the right dosage for every cell type so we don't go overboard and turn them into dedifferentiated cells which could lead to cancer
- Cell specificity, microenvironment, etc.: reprogramming is finicky and the right dosage is dependent on the cell type or the environment around the cells. This is important because you have to figure out the right dosage for each cell type so as to avoid cancer
- Delivery: it's easy to deliver gene therapy to skin cells on a dish, not so much to other cell types or organs in the bodies -- that's why we have not seen very impressive results when this is used on live normal mice
To note, a huge market segment is are already paying thousands of dollars per yer, right now, on skin care (for instance the SK-II lineup sells well, and it’s 100-250$ a bottle)
My semi-cynical view would be that cosmetics companies don’t have any specific incentive to accelerate the natural march of research as long as they stay on the forefront of it and have top of the line products. Basically they’d only have issues with new players making bolstering entrances and disrupting their market with a revolutionary products they’re not ready to counter.
And the gap between some process being validated, and a product with that process being on the market is so huge, it’s hard to see a non entranched company start investing on that without getting noticed.
I’d see it as the same situation as Camera makers when digital was coming at the horizon. They only needed to be there when the tech is ready, and had no need to bet the farm on making it a reality sooner than necessary.
I looked at the Linkedin information for a few cosmetic companies and found that most of the employees work in marketing and channels, followed by business administration, and followed by a handful of cosmetician. My guess is that either research and development are outsourced or they are primarily marketing companies, which means there might not be any research to begin with.
The reason for this is simply sad. Imagine you are a woman in your forties, fifties and so on. For your whole life the society was communicating to you in different ways, directly and indirectly, that a large share of your value lies in your beauty. Now it is fading away and there is no going back. So you do what you can to slow this process down. If you believe it works, you simply feel better. And when you tell it to your friends, of course they will support you ("This cream really works miracles, you look so much younger"). Same with cosmetic surgeries, for some people it verges on the bring of psychiatric disorder, with one operation after another turning you into a monster, but when you look into the mirror you perceive yourself as more beautiful than before.
Is this really still true? I know of many female professionals who are respected for their skills alone
I notice that this beauty standard is mostly kept alive by women themselves. Men care a lot less about the appearances of professionals, especially if they're women. It also depends on the industry. Women in engineering seem only really to be judged by other women outside of engineering. Maybe this is why you haven't noticed it?
The societal biases that disappeared are almost excluse those that are so long gone that we have little chance to even know they existed.
If somebody came up with a product that actually did work, they know they would be in deep trouble.
One of the biggest investors in digital photography was Kodak, because they recognized the threat to their film model. Now they used their patents to stall the conversion to digital instead of using their lead to dominate a new market, but it's not uncommon for companies to invest hard in their replacement to secure IP. That's why MS was getting paid $5/android phone for a while.
I kind of hate to say it, but isn't this why patents exist? The first company to make a product with this tech will have exclusivity for 20 years. Shouldn't that be a sufficient incentive?
Instead, patents are used defensively, for obvious things and rent-seeking. Why is that?
I'm not sure, but I can imagine a combination of:
* You don't have to prove your invention works.
* Patents can be vague and broad, and the non-obviousness bar is depressingly low. Low effort patents have more power than real advances.
* It's hard to enforce patents on in-house processes and systems.
* Workarounds can be found after you've done the hard work.
* Basic research (e.g. algorithms) can't be patented, and basic research is the hardest part.
We really do need a system that makes basic research with high eventual impact profitable. Brilliant scientists are getting paid peanuts.
Certainly, the first company to the market with a drug is usually rewarded pretty heavily, until generics come online 20 years later.
for instance, Prozac was a breakthrough (the first SSRI), but it was easy for other companies to make their own SSRIs.
For instance Kodak was first on the ground with their digital camera, but we all know how it went. The same way pharmaceutical companies patent drugs but it doesn’t stop a rival company from doing their own development cycle and coming up with a competing drug based on the same molecule.
Side question: do these skin care products work? Is anyone here on HN using them and notice any difference?
Those are the big three that dermatologists will recommend that have evidence of efficacy for anti-aging.
Everything else: The Ordinary
Lotion in general does a huge amount to help skin stay healthy and accumulate less exposure damage over the decades.
I'm not so sure this was really true. For example when the mirrorless transition happened Sony had basically bet the farm on making it a reality and as a result they dominate the mirrorless space in marketshare. If a new product is sufficiently better than existing ones then it can overcome the capital advantages of existing players. Especially with modern day VC funds pumping billions into high growth startups.
I also think you have to consider that very few people in legacy companies have cutting edge expertise. Walmart is not going to have the calibre of robotics, AI, or engineering personnel that Amazon does.
They had a CCD/CMOS group company since the 80s and started using them in video cameras. From there they also produced sensors for feature phone, smarphones, and mirrorless was more or less an extension of that
This is where the "competition" pillar of capitalism comes into play. All producers would naturally benefit from being a cartel, but in practice the benefit to the One Player Who Cheats (in this case, by developing better products) is so large that we end up advancing anyway.
There’s a peloton running ahead, and they want to keep a sane distance from the pack. They’ll watch and react to the pack getting closer, but won’t be sprinting their lungs off until any of them gets in reaching distance of the goal.
Except when one of them decide to take the gamble (“cheat” as you say) and start sprinting. But we can agree it is extremely rare to have a sole sprinter leave the peloton mid-race and stay ahead until the end.
When it comes to huge international companies with billions and billions on the line, I expect even less of them to make huge gambles and try escaping the peloton with no goal in sight for the next 15~20 years.
Telomeres are the ultimate clock for cells that differentiate.
Well you are correct. Altos labs (https://altoslabs.com/) is basically every "who's who" in science doing this with billions of dollars. Including Wolf Reik who is featured in the article.
The field of molecular biology didn't exist before World War II; after, a number of funding managers at NIH recognized that there was an incipient science to augment biochemistry and other fields, and funded it through places like Rockefeller Institute (https://pubmed.ncbi.nlm.nih.gov/25862750/).
The long term impact of these early scientists and funders who recognized the potential of MB has been enormous; it lead to the discovery of recombinant DNA, and many other important things which produced an explosion of research.
where I drive to work every day, there was only one biotech (Genentech) campus and now there are probably 20-30 different companies with enormous well-outfitted research labs all stuffed into one little corner of South San Francisco. "Overnight", biotech became a huge industry- overshadowed by the enormous tech industry- but in many ways, the "tech" part is ripe for disruption in ways that look just like the tech industry in 1997.
Either way, it will be interesting to see what is the state of the art 30-40 years from now, assuming the research infrastructure continues apace.
Rogaine and off-label finesteride don't quite cut it.
The basic issue is, and remains, that certain cells die the more and the longer they're exposed to DHT. To solve male pattern baldness, you'll have to reduce your DHT levels, either by reducing your testosterone levels, or by taking brutal dosages of finasteride.
Trans women actually do that, and can stop and even reverse male pattern baldness most of the time. But for cis men, this solution is obviously inadequate.
I think it would also have a profound impact on society and culture. Just how we think about the world differently as our lifespan extends. I think that makes a lot of people scared.
Discussing this with others I see a few things people are highly concerned with but I'm unsure if they would actually happen (as in, I'm uncertain either way). The first is over population. The reason I'm not convinced this would be a problem is that most western countries have declining populations (without immigration) and world wide we've seen dramatic reductions in birth rates. World fertility rate is about 2.4 (replacement level is 2.0)[0]. The other aspect is political. People think change happens on the generation level. But I'm not entirely convinced of this either. We can take attitudes of same sex-marriage as an example[1][2]. A generation is 20 years but our (US) views have changed substantially faster than that. Especially if you include LGBT[3] (I couldn't find timeline sources for European attitudes as easily. Even when looking for specific countries and including quotes). I agree that there's a correlation with generations, but I'm not convinced it is a principle component.
I also wonder how we would think about the future. Interesting to be is that a lot of Eastern cultures typically are more future oriented in their thinking (as compared to typical Western, and I wouldn't say by too much). I would expect that longer lifespans would put pressure to be more cognizant. Would a crisis that is 100 years out seem as far away? Hard to say. We might even have to live with longer lifetimes for awhile for that to happen.
All I know is that it would cause big changes. But I'm not sure that should stop us from pursuing this technology unless we see major pitfalls ahead of time and find that they are insurmountable obstacles to overcome. There are clearly issues with increased longevity (especially the disproportionate use of it) as many dystopian SciFis have pointed out. But I think it is better that we at least discuss these things in the open since the technology itself is no longer in the realm of fantasy but has graduated to the realm of possibility. There's too much money being put in this technology now for us to not take the questions of the impact of it seriously. Even if 10+ years out (even 50+) I don't think we should dismiss them. If we're talking about culture shifts, maybe one of the best things we could do is talk about the impacts (pros/cons and how to use them in fair and equitable means) of technologies before they are here. Maybe we could have some of that discussion here?
I'm normally not a big CGP Grey person, but I do like this video on the Fable of the Dragon Tyrant[4]
[0] https://data.worldbank.org/indicator/SP.DYN.TFRT.IN?location...
[1] https://news.gallup.com/poll/350486/record-high-support-same...
[2] https://www.pewresearch.org/religion/fact-sheet/changing-att...
[3] https://news.gallup.com/poll/1651/gay-lesbian-rights.aspx
It’s an interesting exploration of the topic.
I don't think so. Once something is out and proven to be cost-effective, even expensive treatments, it proliferates into the top 5-10 per cent of the world's population pretty fast.
I love your username too.
Hey I maybe maybe might be alive by then too! Who knows.
There's life after death.
But preventing aging isn't yet possible, so there is more sense of urgency around developing anything that helps.
Thanks for compiling and condensing all the information into a blog post.
See, I went camping with the Scouts on Isle Royale, at the end of the week we were comparing mosquito bites, averaging about 100 per. Then a young man Luke said offhand "Mosquitoes don't bite me."
And sure enough, his skin was totally clear. I said "Luke, you bottle that, you're a millionaire."
A man who studies ticks was bitten so many times that his body developed antibodies to tick saliva, which are now so powerful that they kill the ticks.
I recently managed to coax one into biting me to test my hypothesis. I felt it go into my skin and watched it suck for a bit, but it didn't get particularly engorged on it. No mark the next day. My son had a bitemark from a non-deliberate bite, though.
It seems to be a known phenomenon (though I have no idea why it happened to me): https://outdoors.stackexchange.com/questions/4310/is-it-poss...
It’s quite a luxury as someone who spends lots of time on trails. But I also feel somehow offended. What’s so bad about MY blood?
So its likely about how that smells
Or other trails toward you, while they probably would enjoy your blood in actuality even if they think they’re detecting something related to how the meal would taste or its nutrition levels by proxy
Let me know what you all know!
I thought the theory was that they follow the CO2 we exhale.
There is still some difference in who they choose to follow or act upon so I’m grasping for where that difference is. Could be something alongside the CO2
I guess I’m less into the semantic difference between “smell” and “detect” and more whether it’s the CO2 they’re following or something else we exhale regularly.
But, to be fair for me being fit and being in the regions where mosquitos exist en masse is a related phenomenon. Out of shape me spends less time on trails than fit me.
How would they know your blood type before biting you?
> I felt it go into my skin and watched it suck for a bit, but it didn't get particularly engorged on it. No mark the next day.
So it might follow that with one resistant (R) and one non-resistant person (NR) exposed to a few dozen mosquitoes, NR will end up with lots of visible bites while R will be relatively unscathed - even though the mosquitoes might have sampled them each equally.
I know too that some mammals (e.g. mice) will sample a small amount of food (e.g. rodent poison), and then return later to try more if the food hasn't had ill effects.
I'm not sure that mosquitoes have anything like a memory capacity for this, but maybe something similar mediated via pheromones could be happening. (And something like pheromones could also signal to other mosquitoes that there's good eatin' to be had).
Or you get assassinated by Big Mosquito Repellent. I wouldn't mess with those people. Stick to inventing a cheap carbon-negative replacement for gasoline. Far fewer people angry at you upsetting the apple cart.
Put another way, we've been going to war over oil for years. One more body on that pile isn't difficult to imagine.
off by about 3 or 4 orders of magnitude unfortunately
That seems less likely than "My body doesn't generate a histamine response which results in a raised bump at the bite location."
So in my case, I do have a response to at least some bites, but consistently fewer than anyone else I'm with.
You can quickly confirm whether it's no biting vs no reaction by the fact that you can see them flying around and landing on you. Or rather, around everyone else except you. They aren't invisible. Here in the tropics, other people will be covered in them.
Any solution that involves stem cells needs to also massively reduce errors in DNA replication, otherwise cancer would occur.
Their larger size is due to more cells (not bigger cells), so they would be more at risk of cancer. But they've evolved to have more TP53 genes, so their lifetime risk of cancer is around 5%:
https://www.nih.gov/news-events/nih-research-matters/how-ele...
Unfortunately untrue. You are referring to https://en.wikipedia.org/wiki/Peto%27s_paradox but as you say 5% of Elephants still die of cancer. Elephants have evolved other mechanisms to protect against cancer because they have more cells (more copy errors) https://www.sciencedaily.com/releases/2021/02/210204131438.h...
When thinking of cancer, try to think of the incentives of the organism to avoid copying errors, which are eventually deadly. So many deaths are direct effects of copying errors (cancer), that the human body gives most cells a lifetime of ~40 duplications (https://en.wikipedia.org/wiki/Hayflick_limit measured by telomeres) before killing off cells (cell senescence). Senescence causes the majority of other deaths i.e. the root cause of death is often indirectly due to the body’s mechanisms to prevent cancer. The mechanism to cause senescence has to be robust to error, so that mutations are unlikely to defeat cell death. A metaphor: the body tries to keep the tree of all cell duplications as a balanced tree - and cancer is when one node has enough error that it can reproduce and unbalance the tree.
https://royalsocietypublishing.org/doi/10.1098/rstb.2016.044... links to better information, and it has a lovely summary: “We assume that selection favours short telomeres as a mechanism to protect against cancer. At the same time, selection favours long telomeres as a protective mechanism against DNA damage and replicative senescence.” We have evolved compromises that protect us against DNA copying errors, but those compromises are imperfect (from a longevity POV).
Cancer is an area where there is extensive misinformation as to the root causes, and “the cure for cancer” is non-sensical: the cure would require eliminating DNA errors in all cells within the body. Currently we can fix some individual errors (specific cancer therapies), or attack dividing cells.
As well as all that, elephant cells are intrinsically more cancer resistant as you point out.
After I found out about this, I now view all other cancer research suspiciously. Them trying to maybe cure one specific type of cancer by blocking some specific protein now feels like they're trying to fix a bug in a react web app by carefully loading a crudely written kernel extension into the OS. Yes, it's technically possible, but wouldn't it make more sense to operate on the right abstraction level?
We can work on different abstraction levels because in the worst case, we can just crack open a hex editor and write raw assembly or mess with the OS directly. We've built on that to get C, and Java, and Python, and all that other good stuff, but we can go all the way to the bottom if we need to.
Now imagine you're working on a computer with proprietary hardware. The easiest way to interact with it is via a provided high level language, like Lua. This is eating, drinking, sleeping, exercising. Now imagine that you crack open the assembly because something is just not working right. Some illness or something. And you come to realize there are thousands of different opcodes (proteins, enzymes, genes, etc.). Not only that, but sometimes they work differently depending on where in the computer they are located or the time of day or whatever (organs, menstrual cycle, circadian rhythm, etc.). You can make some good guesses on what a couple of them do, but you are not sure of the entirety of their effects for the majority of them.
So you're looking at the interfaces and you figure out if you send the right data to this and that place, you can get it to work right, maybe with some acceptable or unforeseen consequences. This is medicine, and it is a miserable way to do things due to the complete lack of understanding and control, much like driving your car from the backseat with a 10 foot pole while facing backwards.
So you've discovered a lot of hacks, made a lot of medicine, collected a lot of 10 foot poles. And as you look at your ever expanding collection, now easily in the thousands, you begin to get the creeping feeling that (a) you will never find a panacea, (b) the system you are working on is a disgusting mess of patchwork jobs on patchwork jobs developed over millions of years, and (c) there is probably an underlying system directing all of this, but its complexity might not even be better than what you're operating on now, and you definitely lack the technology to utilize it properly anyway.
And what you're doing is saving and bettering people's lives on the whole. And then some big shot comes in and says "Ackchyually, why don't you just access the lowest layer directly? Pretty sus." Try to have some perspective and humility on how horrifically complicated biology is. Life was evolved, not designed. Life isn't a computer. The relative simplicity and sanity of technological systems is a blessing absent in biology.
Biology is not programming, except when it is like programming, or when it involves programming. But that could also be said about golf.
A lot of people have imagined that. But nobody does.
Potentially cancerous cells are constantly being produced in the body and then killed off by the young and functional immune system.
Keep the immune system young and functional and most of the cancer concerns are not terribly concerning.
or some kind of therapy?
You think there'd be something found in the last 20 years, people can agree on, that's been helpful to prevent aging?
is there something like that?
Fisetin among others seems to have some promise, however how much this will impact lifespan is unknown. Fisetin probably not much, partial reprogramming (OSKM etc) maybe a bit more.
This seems to be building on things that were revolutionary already.
Might want to read the article. But there is no medicine to take yet.
I could see a shot or supplement in the future targeting a variety of cells to halfway deprogram for the youth affect.
Rapamycin and metformin. Both have anti-aging effects. But experiments to prove this on humans are hard to replicate as it involves studies of humans dying of old age. You'd need probably 20 years to run such a test.
So they have shown this for mice and rats. BUT, there are side effects. Also I don't think these things reverse aging, they definitely slow it down though.
I know rapamycin specifically works on MTOR which is identical to what happens with fasting. Too much rapamycin though isn't good.
[0] https://www.health.harvard.edu/staying-healthy/do-retinoids-...
Retinol, niacinamide, acid treatments, vitamin c, sun screen, botox, microneedling, etc.
Is there any skin agent that can be used from a relatively young age, where the usage will pay off at a later age? Again, except for the sun screen.
If I were faced with a choice where one option is my own immortality and of those who I care about, but also accompanied with a path to immortality available to every tyrant and sociopath at the top of the wealth pyramid, and the other choice being that we all continue to pass on at the usual rate, power and wealth having no real say in the matter - as much as I’d like to hang around longer, I would be agonized by the implications of such decision and am not quite sure what I would pick at the end.
Here's a full list: https://twitter.com/adanguyenx/status/1512138722556334090
I didn’t even see a link, but there were so many ads it was hard to tell.
So, just like I nowadays must strive to get a sense of the real person behind all the makeup, lip filler and botox, I should in future expect to have to differentiate between real people and synthetically and genetically enhanced such?
Well, I'm sure there is a big market opportunity here. But I'm not sure I like it.
Please just don't oppress those who disagree. Especially when this type of research can save lives.
You final line is puzzling. How could I possibly "oppress those who disagree"? Because I assume you can't mean that I should simply shut up? As for saving lives, I'm all for saving people from dying before their time is up. But it is probably time to accept that we can't go on curing people forever.
Just like a tree falls over and goes back to the ecosystem after a set number of years (give or take), we as humans are not constructed to live much longer than 100 years (give or take), and that is not a tragedy. It is life.
I said LGBT, not "gay" on purpose.
>Because I assume you can't mean that I should simply shut up?
I mean don't vote to ban research, much like many did for stem cell research which probably collectively set back all of humanity.
Look at what's happening in Japan, where the young struggle to get a job because their elders are retiring older and older. Now imagine, they never retire because they are immortal. The only way someone dies is by accident of if someone kills them. How would such a world not devolve into a dystopia?
The essential difference is this: the quest to extend human life span beyond the encoding found in the genes of our species is obviously different than trying to essentially reach the predestined life encoded in the genes of our species. This is why we experience tragedy when someone "dies before their time", especially children, but also young adults and so on up until the non-tragic but nonetheless sad deaths of 100-yearolds, who had lived a "long and fulfilling life".
I'm sure this does not convince the hardened transhumanist of the qualitative difference, but there you go. It's how I look at it anyway, without knowing exactly how we can control the current scramble to obtain and exploit the crucial IPs in this domain.
To show the absurdity of the position, consider a person who undergoes Lasik surgery, or wears glasses, who need to have surgeries for scoliosis, consider color blindness. Under the appeal to nature, we should not be helping people for any of these issues precisely because we going against what nature intended. This also includes caesarean surgery, absence of which could leave millions of women and newborn children to die.
This is because you paint what we call a strawman view of my position, and argue against that. It is common among students probably because one has recently discovered the power of abstraction and reduction, but gets gradually more rare as you approach my age (approaching 70 years old), where these kind of argument tricks have been dismantled a thousand times or more.
Instead of assuming that I'm an idiot, maybe you should assume that I have already considered the simplest counterarguments (see sibling reply). Come to think of it, isn't there there something along those lines in the HN guidelines?
The image that you portrayed of yourself is that of a vain person, one that limits themselves to appearances instead of inner qualities such as a person's inner world, beliefs and views. You chose to express that your filter is first and foremost a superficial one, you chose to express that people who have corrections to their DNA for example are somehow less of a __real__ human here:
> I should in future expect to have to differentiate between real people and synthetically and genetically enhanced such?
The immediate implication of this position is that correcting a person's genes due to a slight error, e.g. androgen insensitivity due to AR mutations, makes them less of a human ergo do not deserve the same treatment and rights as everyone else. In contrast, correcting for such issues would reduce the probability of cancer in this case, enable the people to have children and avoid a whole class of DSD.
You painted that portrait all the way through, nobody else.
Perhaps the inability to grasp the consequences of such positions is an argument as to why I should not have bothered.
Maybe next time we can discuss issues instead of figments of imagination. Until then, have a good day.
Since time immemorial. Pretty much every religion promised eternal (after)life
One might actually expect there to be an objection to transhumanism on these grounds. But I haven't given that much thought honestly - I'm not religious.
Open question [ELI15]: why can’t we tissue culture scalp skin for hair, like we can skin in general for treating burns victims?
ETA: question.. why aren’t we able to regrow teeth and enamel? Imagine..if we can reverse cavities and no more root canals ever?
https://www.theguardian.com/science/2019/aug/30/scientists-g...
But perhaps only the rich could afford it, in which case having children would be a sign of being lower class.
And I imagine it would lead to widespread murder, as those appalled by the notion of immortality would try to take out those that embrace it.
Has any (good) science fiction even properly dealt with this kind of dystopia? I would like to read it.