By 4% which may as well be experimental error, right? The mice could have very well just lived longer due to increased interest/handling/measurement of their welfare.
This seems insignificant when compared with other selector genes such as H63D and C282Y, which could potentially double or halve subjects life span depending on environmental factors.
I would hope that they controlled for such systematic effects in the experiment (did not read the paper) by mixing individuals from both groups (my guess would be that they do not look different). I guess they should have also modified some other random gene in the control. Did they actually?
However, I find it very interesting that all those important details seem somewhere hidden in the paper. Also I guess if you consider a 10x increase between the species and then end up with 4% this sound really far less spectacular.
Doubling lifespan is definitely a bigger impact than 4%, but let's explore what the hypothetical "perfect application" of this study to a human life.
A fairly average lifespan is 80 years, so a 4% increase would be about 3.2 years. If I were offered a "wonder drug" that would give me 1,168 more days with a loved one, I would take it.
Obviously that is not how science like this works, but stacking small victories over time is a way to achieve "significant" impact.
Hm, would you go through the process of GM your (otherwise naturally conceived) kid on the chance that their lifespan would increase by 4%? For me personally, OK, 10% ... maybe, 20% definitely.
But what stigma and complications/risks could they live with for a 4% increase in lifespan? What if they find out in 30 years time that their GM means that they can't have kids with their partner or something because there is some biological incompatibility that wasn't anticipated and it just miscarriages. What if some country is Xenophobic to the idea and won't grant them residency or a passport because they are GM, or they are eventually targeted by some kind of anti-GM hate group? Would that 4% be worth it? Like everything it's a risk-reward value prop.
Biologic incompatibility isn't as much of a concern. At least not with the modification in the article. Our genes encode a wide variety of proteins and enzymes that differ from person to person. Even people with significantly debilitating mutations havent had trouble conceiving. Even people with extra x or y chromosones do not have to worry about the matter. Though some men do have strange mutations like only being able to conceive girls with their partner.
I know there's the replication crisis and everything, but let's not be over cynical - I don't think Nature would publish a study that didn't use basic statistics and didn't have a control group for its experiment?
Typically Nature or high impact journals are specifically more likely to publish irreproducible studies.
It's very similar to the well established fact that students with good grades are the most likely to cheat.
If you want to look for solid research, don't look to Nature, look to the so called "mid tier" journals.
Also, similar observations are true for research groups. Research from ivy-league universities follows similar principles as above.
I would really like to see the end of aging and by that I mean the end of age related disease, dying from ALS or Alzheimer's disease (which both are by and large age related diseases) is not nice. My mom has ALS and it is tough.
I don't see much other hope in curing these diseases tbh, it feels like the research is going nowhere so I am somewhat excited about longevity research and glad that someone is pursuing it. If I didn't become a software developer, I would like to work in that field
Alzheimer's just had two drugs approved by the FDA for treating the disease. They're certainly not a cure, they only slow the onset of symptoms by removing plaques from the brain. The underlying factors that cause the buildup of plaques still aren't well understood.
That said, I would still put much more hope in the research into well-defined, specific diseases such as Alzheimer's than I would into aging or longevity research.
There are several reasons for this. First, the absolute bedrock foundation of all of medicine is human trials. There is no substitute for actually trying drugs in humans and seeing what happens. These human trials are possible (albeit extremely expensive and difficult) to run for drugs targeting specific diseases. They are functionally impossible to run for "aging". What would the trial test? Just all-cause mortality? That would be an impossibly noisy target, and almost guaranteed to fail. Not to mention that the trial would have to last an incredibly long time to test any benefit for younger people. No funding agency and certainly no drug company is going to take that bet.
The second reason is that aging is a property of the entire organism. Like, every gene and every cell is affected by aging. It's simply impossible that any one gene or one drug is going to have a significant effect on aging. Drug development is currently entirely oriented towards targeting individual genes and proteins. The reason for this is that targeting even one protein with a drug stretches the limit of our technological abilities. Two drug combinations are relatively rare and are typically limited to diseases like cancer that have well characterized causes at the molecular level. This is not the case for aging. Again, aging isn't well enough defined to even pick a specific gene that "causes" it.
But for ALS sadly there is like nothing, absolutely nothing meaningful. My country doesn't even allow assisted suicide so your option is basically to go to Switzerland or degenerate here and die when you cannot breath anymore.
I am by no means expert in this area, but there are some epigenetic aging clocks that are based on some machine learning models, and supposedly they somehow show your "true" biological age and predict death quite accurately. GrimAge, epiage etc. Sometimes I have wanted to take that test but haven't bothered.
I dont think you will whilst inflammation is seen as something bad. If you look at what causes inflammation, like zinc, inflammation not only destroys the pathogen, but also destroys surrounding host "healthy" tissue.
Now if elevated levels of zinc cause this inflammation, the new tissue that replaces the destroyed host healthy tissue will have elevated levels of zinc in the cells compared to the previously destroyed "healthy" tissue.
Ergo, is this the body's way of using minerals to increase the anti bacterial nature of the cells in that part of the body, and why all inflammation should not be seen as a default bad thing?
I don't quite understand the premise of longevity research.
Isn't there a concept similar to "no free lunch" in biology? Infinite, cancer-free lives sounds just too good to be true. Something sounds off about that.
> Isn't there a concept similar to "no free lunch" in biology?
Not really, no. There are examples of complex multicellular animal life with negligible senescence: some species of tortoises, of sturgeon, naked mole-rats — they don't die "of old age", only by illness and violence.
But even if there was no free lunch, we might just be able to pay the price in a way that evolution can't; I'd be very surprised if we could even engineer a gene for an organic MRI machine, let alone have one evolve naturally, but we can use what genetics evolution gave us to build a machine to liquify helium to turn unnatural rocks into superconductors to peer within our bodies and look for growths.
I think it's interesting to consider in evolutionary terms: "what's the tradeoff?"
Why is there the proportion of Methuselan species that there are? Why not more, or less?
One simple take is old age is adaptive: the longer you live, the more chances to mate, the more offpsring, the more likely that your genes survive, perpetuating it.
One simple counter take is old age is not adaptive: the longer you live, the more your learned skills (or "maturity bequeathed survival" in the species where it's hard to say they are learning something), permit you to steal resources from the young, lessening the chances of survival of all offspring, on average. (you may take issue with that implication but you can also see how it is true, or better yet come up with another counter take!).
A second simple counter take is each generation lives longer so there's less evolution.
I think that in a species that learns, has a big brain, and is already adaptive, it makes sense that it will try to live longer because it's primary survival advantage comes not from its evolutionary legacy but from its accrued learnings (one may dispute that, or get pedantic and say "but without the original evolution you couldn't have the accrued culture", but you can also see how it's true), so even tho it's not "evolutionary"-based adaption, it's "self tinkering"-based adaptation. The longer you live, the more you learn, the better your chance of survival. Even if not evolutionary, you "Beat the gene", and make your culture, (and yourself, and all Methusalan individuals in it) more likely to be alive...rather obviously I guess.
So if we do come across aliens from such a species (like us, or orcas, or other big-brained, learning species, but more advanced), then it's likely they live a looong time. Unless they got fussy about some ethical issue with doing so, and decided against it. But any ethics involved seems unlikely to be proscribed by a constraint on energy capture / resource usage...as that would likely be one of the other characteristics of such a civilization, by virtue of us having been able to encounter them, it seems they were already able to master that. So it's highly likely that they live a long time.
So maybe, those "longevity gap" situations that people are so fond of agonizing and preaching about...are already the case on a cosmic scale, and the present race of humans are currently the beneficiary of the "less fortunate position".
Interesting to think tho, has the first child been born that will be the last generation to face death?
Arguably longevity may not be very meaningfully beneficial if you have a slim chance of getting old in the first place. You also must consider human reproductive design where eggs aren't produced on demand.
Ah, that's a good one, yeah. So you need a lack of natural predators and stable environment. That's true about reproduction as well, so evolutionary fitness of longevity favors males, but not, necessarily females after menopause. Part of human longevity may also be to extend female fertility...if women want that!
It's amazing what you can explain with evolution. I wonder how much of it is real and how much of it is, "well, it sounds like it makes sense."
But this definitely makes sense.
I'm not sure how you could explain "career woman" tho, who chooses not to have kids. Tho I'm sure there's like a civilizational advantage to that behavior (aside from the obvious "economic" ones).
I suppose an argument could be made that, people prefer other people who share similar genes, so a powerful woman who rises in the business world, can then favor those with whom she shares genes (and increase their reproductive fitness, if not her own directly), thereby increasing the survivability of their offspring. The same could be said for a man, however. I don't think that makes a difference. In a sense, those who eschew their direct line to accrue worldly power may end up benefiting their "genes" in a different way to those who reproduce conventionally.
Not to take a negative slant at all, but humorously, a sort of post-modernist "deconstructed" nepotism, I suppose, haha!
What was Fukuyama's argument in end of history, again? I don't know, but I suppose at some point you get an "end of evolution" where civilization takes over and there's no obvious "reproductive fitness" any more to explain behaviors, it's more like "civilizational fitness". But, looking at the above, it seems that our genes may run rings around such suppositions already! Our clever genes! So very selfish!
One note in your link: I saw It also fails to explain the detrimental effects of losing ovarian follicular activity but I disagree, I think that physical decline provides opportunities for relatives to provide care, which likely increases social bonds, and enhances the Grandmother's "genetic nurturing" Effect. So if we assume the original hypothesis is true, physical decline would be a development that supports and enhances that effect, and so likely to occur. A truly noble sacrifice, on the part of the Grandmother, and all at the hands of the selfish genes, haha!
Why would there be? In the end we're just biological machines, albeit very complex ones. We're made of physical matter arranged in a specific way, physical matter can be manipulated. This means that if a biological machine is damaged or wears out, there is nothing that fundamentally prevent us from repairing it. The only thing that is needed is a proper understanding of how things are supposed to work, i.e. the desired working state, and the tooling to perform the repairs.
Sure, nothing fundamentally prevents us from repairing it from a physical standpoint. The practicality of it is the key question. While the machine analogy is partially useful, genes/proteins/cells are dynamic, adaptive, and can exhibit stochastic traits. This fundamentally contrasts them from traditional machines, and is the reason (imo) we suck at making effective therapies to even treat diseases where we think we know what is going on.
But practicality is just a technological problem. And not to make a fine point of it, the chips of the machine where you are writing or reading this receive far more “technological attention” than any human being. That fact in itself is not a technological problem, but a social one. In my opinion, at our point of technological development, aging is about 80% a technological problem and 20% a social problem. The speed of research and development in technologies to combat aging, i.e., the derivatives of the numbers above, are probably in an opposite proportion: 95% of the slowness in research can be attributed to social problems, 5% to technological.
"Isn't there a concept similar to "no free lunch" in biology?"
Is there? Is this a widely accepted scientific fact? What does this even mean? That you can't get a benefit without a cost? I thought that this phrase comes from economics. I think you're thinking of economics which is... not human biology.
"Infinite, cancer-free lives sounds just too good to be true. Something sounds off about that."
So just accept the fact that we all die and not learn about our bodies? I mean I don't know; some of us value being alive and prefer to stay that way if possible. Do you not also see dying as a problem?
If you were to know that you were going to die tomorrow you wouldn't see that as a problem? Or is it only not a problem if you die at the sort of average full human lifespan age of ~70-80? Why is dying then ok and not tomorrow?
You see I'm also a human being such as you who values life and people. It's a bit harsh to comment about my world view sarcastically like that.
I was just voicing something about the process: biology is a complex thing and longevity is not attacking things from a metabolic, complex-system viewpoint. As we see here, we are after single pills or single gene activations to carry us to a healthy state. I doubt infinite health unlocks in such form.
Another point is, if you transform yourself to this new state that's immortal but lose most of the biology that makes your body human, what does it mean? (reference to Leto Atreides II here maybe)
Why do people suddenly make it unethical to view death as most-probably-inevitable for human beings?
There’s a big difference between being immortal and not having to die at some preprogrammed time that is purely a byproduct of our evolutionary history. It’s a spectrum.
We don’t know what it will take to make us healthier/love longer.
All we are doing is trying to understand our bodies.
All cancer and heart healthier research is also trying to effectively increase human lifespan. So are anti smoking campaigns and seat belts.
No one would comment the way you did for these. We just take these for granted as a good thing.
But trying to understand the genetic basis of aging is however you put it.
There are other mammals who live much longer than humans. Evolution optimized for continuation of the species, not longevity of the individual. So there is absolutely optimization room for increasing human lifespan.
> There are other mammals who live much longer than humans.
This didn't ring true to me so I did a bit of reading. AFAICT there's one[0] species of mammal that can live much longer than us. We're at least tied for second-longest lifespan of all mammals.
I think you should look at it in terms of lifetime calories burned per unit of body mass. Most mammals have very similar lifespan measured in this manner. With the exception of bats. Because they really needed to burn way more calories, so they figured it out how to do it without accumulating damage to their bodies that eventually leads to death at the same lousy rate that all other mammals can get away with.
This is a reasonable question - we might have found some sort of "no free lunch" theorem! But as others have pointed out, so far no such inevitable tradeoff has been found, which in itself supports the view that it won't be.
There is Mikhail Blagosklonny's theory of programmed aging, in which aging is a byproduct of helpful developmental processes. This does seem to imply we need to mess with some pretty fundamental metabolic processes (hence mTOR inhibitors). That's close to what you're suggesting, but it still seems achievable.
Since all organisms are made of somewhat-similar cells, the bristlecone pine, the immortal jellyfish, long-lived tortoises and so on, are all important existence proofs that negligible senescence with no ill-effects is possible.
As they say, the goal is to die at age 150 with the body of a 30-year-old in a freak skydiving accident! It's been good to see longevity research move decisively out of crank territory in the past 15 years.
> Isn't there a concept similar to "no free lunch" in biology?
There's a difference between "there are probably trade-offs here" versus "this is impossible because otherwise it would have happened already."
Consider that land plants evolved lignin to grow tall, leading to gigatons of free lunch sitting around for tens of thousands of years before anything else found the trick of digesting it.
If there weren't any free--or at least below-cost--lunches out there, nothing would evolve, because there'd be no benefit in changing anything.
Those animals (e.g. tortoises, lobsters) with longer lives combined with less cancer have significantly lower metabolisms and a far less ... intense ... lifestyle.
Higher cellular respiration introduces higher chances for mutation / inflammation / cell damage. Likewise, high rates of cellular reproduction do the same. Every incidence of that is a roll of the dice for cancer. Extend the lifetime, and you will for sure get cancer, because you already have a very high chance of it.
Evolution in our species has arrived at a set of trade-offs. We don't understand them all yet.
It's a very valid point. Our past meddling with ecosystems and biologies have often produced unintended consequences to great detriment, it's not hard to imagine those from this too.
Even ignoring the biological risks here, the economic risks are quite obvious - we're already in a place where many developed nations have demographic problems where ever greater percentages of the population no longer work, leading to less and less resources available to support the pensions of later generations.
Imagine if all the people who are currently retired got this naked mole rat gene and lived an extra 30 years.
What I do like about the article is that at least part of the longevity comes from reduced incidence of cancer. That's a medical treatment I can get behind.
> Our past meddling with ecosystems and biologies have often produced unintended consequences to great detriment
…we also effectively eliminated hunger, whole classes of diseases, and greatly extended healthy human lifespan across the planet.
Ultimately I think this attitude stems from the premise that there's a choice of some "stable state" that humanity abandoned, some kind of safe well balanced haven that we left to "meddle with ecosystems". There isn't, "ecosystems" tried their best to kill us at every point of our history (it seems there was a moment there were just a few thousands of us, nearly wiped out by a natural catastrophe!), and the only way to avoid that is to "meddle", learning from our mistakes and becoming better stewards of the planet.
We were, are, and always will be walking on a tightrope, we are just learning to do it better.
Unfortunately meddling with humans is not something that is very possible or accepted. This is one of the primary reasons we’ve made almost zero progress recently in understanding ourselves.
The fact that these naked mole rats live 30x longer than other rodants suggest life spam can obviously be controlled. Anyway, I can imagine increased life spam as just costing something (not free) - e.g. you spend more energy on error correction and detection.
the fact that each species tends to live its own lifespan and each lifespan is somewhat unique (like not all species tend to live 10 years, for example) suggests that lifespan is genetically programmed.
There are some good, obvious reasons to not have parents and grandparents around forever in limited resource environments.
I believe that for a species, longer generations means slower evolutionary adaptation to environmental changes.
(at least for our bodies, our hardware. Ideas/technology can iterate somewhat independently.)
(longer lifespan and short generations would probably have caused resource shortages at various points in the past)
What sounds off is that the world will fill increasingly with new people if everyone became immortal...that sounds like a world that would be horrible to live on.
The consequence is a lopsided society where there are few young people and a population that continues to grow. Also, the meaning of young will evolve. To combat this having a child becomes something of an ultra rare privilege, like a green card lottery. Most people don’t get to have one. Because of this, becoming a grandparent because a statistical anomaly. You might think if you get to live so long, you’ll become a great great great great grandparent or something but actually the opposite. Family traditions disappear. When you’re not allowed to have kids and become a family, the dynamics of relationships between men and women change drastically.
With no deaths, wealth concentration grows to the extreme. A handful of people get to control the entire world. And most of those people are strange, so the fate of civilization rests on the off chance that they allow regular people to live a good life.
Society as we know it will be unrecognizable in that future. Whether it’s a utopia or dystopia, I think it’s neither, but does sound a bit dystopian.
"With no deaths, wealth concentration grows to the extreme. A handful of people get to control the entire world."
I rather think the treatment will be so expensive, that only the very rich can afford it - and then you have rich immortal overlords, ruling over the lowly mortals.
But that is not a given. If there is treatment for everyone, it might make people more responsible.
Most people today won't have to feel the real consequences once global warming hits hard. But if they know they might - they might see things in a different way. And this goes for everything, also how to maintain a sustainable reproduction.
As I understand it, you can order 400 genetically identical mice very easily. Eliminating confounds, easy access, quick lifespans (for iteration) and mammals with at least some transferability to humans is the primary reason. Plus, unlike monkeys, no one cares.
Some groups care, and I certainly don't want the mice treated cruelly. But I also am willing to let some mice get experimented on to save human lives. I feel most people are.
I've seen protests against and heard about attempts to free lab monkeys. To the best of my knowledge, there are no similar issues around mice in any significant numbers.
As a pet rat owner of over 8 years, medical research on rodents actually rarely results in benefits for pets of that species.
The main advantage we have found so far is that drug studies done on rats can serve as a reference for safe and potentially effective dosages, as there's very little veterinary literature on rodent care otherwise. All meds for rats are typically repurposed cat, dog or human meds and determining the dose needed for treatment is trial and error more often than not – even in the hands of an experienced vet.
Came here to say the exact same thing, I'd love for my rats to live even 6 years, I always find it a little disappointing so much research is done on them yet they still live such a short amount of time. I suppose a heart that beats at 320bpm doesn't help...
Also: much love to my fellow ratto parents out there, best pet on earth imo.
I see DNA as a code that has been written by nature over millennia.
We don't understand the genetic code well enough to hack or rewrite our DNA to grant us longevity. However, we might discover a species in nature with relevant genetic traits and replicate those parts, assuming that the species is not extinct.
If we've managed to wipe out 70% of animal populations in just 50 years, it doesn't seem like it will take long for those remaining populations to collapse.
Of the last category, about half is mice. And that's just mammals. Look at insects (80% decline), sharks (80-90%), fish (seas virtually empty in 2040's), birds (about 30-50% decline), etc. etc.
The primary driver of deforestation and subsequent biodiversity loss is animal agriculture, which occupies 80% of all agricultural lands. Our industrial agriculture, excluding animal agriculture, is also a significant contributor to biodiversity loss and soil degradation (also a form of biodiversity loss) due to its use of pesticides, herbicides, and over use of fertilizers.
The majority of our pharmaceuticals originally stem from nature. We've just learned to read, and manipulate the genetic code, while simultaneously depleting the largest repository of such code.
And this discussion doesn't even touch upon the ethical or moral implications of such behavior or the theft from future generations or zoonotic diseases ...
A-bingo. Yes, so many of our best technologies were inspired by natural information processes.
Aspirin comes from isolating the biologically active chemical, Salicylic acid, in willow tree bark.
Disc laser technology and nano
-texture paints comes from reverse engineering the moth eye.
The more processed a food is - that is, the more informatic noise it contains, the less signal, the worse it is, nutrition wise. Also from a quantum history moralistic perspective, less dependency = less inputs = better.
Foods that are closer to death or have undergone a death process are largely toxic to the body in terms of biological debt on the inflammatory (cancer, autoimmune, stenosis of vessels, etc) axis.
Fruits, nuts, seeds, eggs, and cheese are closer to birth and if eaten relatively whole/unprocessed, will be absorbed with low impedence/resistance.
The human body is a biochemical engine. It is versatile and can accept bunker fuel, ie. oily processed garbage. But it'd rather have a high protein high fat diet consisting of foods that haven't been dressed up, or gone through chemically dangerous dying process.
Animals can be carnivores and take the route they wish. If we want to live longer, we have to actually understand what food energy is. Because most of our energy comes from oxygen. When we lose fat, 99% is breathed out. Just like a naturally aspirated car engine.
This seems insignificant when compared with other selector genes such as H63D and C282Y, which could potentially double or halve subjects life span depending on environmental factors.