Naked Mole Rat’s Longevity Gene Gives Mice a Longer Life
scienceswitch.com
scienceswitch.com
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.
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.
A nitpick: Those are not genes, but mutations, probably describing variants of the HFE gene (according to a quick search).
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.
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.
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.
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
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.
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.
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?
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.
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?
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 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.
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.
Also take into account that human lifespan in the wild without medical tech is ~40
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 some good, obvious reasons to not have parents and grandparents around forever in limited resource environments.
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.
…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.
Fat lot of good that'll do us if we succeed in cooking the planet...
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.
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.
(Also relevant: Carcinogenesis[2])
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?
I'm reminded of two verses:
Old age should burn and rave at close of day;
and
Age shall not weary them, nor the years condemn.
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!
Some animals live longer than us. Many of them have lower cancer rates than us too.
Seems like a good idea to investigate the possibility of having longer and healthier lives.
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.
Sure we don't understand it all yet, but there's no harm in trying to.
(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)
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.
So yeah, that’s not a free lunch.
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.
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.
Bats must have lots of adaptations in their mitochondrias to how much calories they burn.
And in many variants, for example one’s likely to be diabetic, get Alzheimer’s disease, etc.
If you want to know more of mouse dystopia, visit https://www.jax.org/jax-mice-and-services
> Plus, unlike monkeys, no one cares.
Animal welfare groups do, as does the law in some (most, I hope) countries.
I do, too, but I do realize I benefit from that mouse dystopia, too.
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.
I don't know how enviable is that on average. Most experiments don't end up with a discovery, let alone a discovery of something beneficial.
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.
Also: much love to my fellow ratto parents out there, best pet on earth imo.
The primary driver of biodiversity loss and deforestation is animal agriculture.
Act accordingly.
https://www.pnas.org/doi/10.1073/pnas.2204892120
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.
https://www.theguardian.com/environment/2022/oct/13/almost-7...
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.
- More losers than winners: investigating Anthropocene defaunation through the diversity of population trends [https://onlinelibrary.wiley.com/doi/epdf/10.1111/brv.12974]
- The climate crisis and biodiversity crisis can't be approached separately [https://phys.org/news/2023-04-climate-crisis-biodiversity-ap...]
https://ourworldindata.org/wild-mammal-decline
Wild mammals have declined by 85% since the rise of humans
https://www.pnas.org/doi/10.1073/pnas.2204892120
The total mammal biomass:
- livestock (≈630 Mt)
- humans (≈390 Mt)
- wild marine mammals (≈40 Mt)
- terrestrial wild mammals (≈20 Mt)
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.
https://ourworldindata.org/drivers-of-deforestation
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 ...
- Biodiversity conservation: The key is reducing meat consumption [https://pubmed.ncbi.nlm.nih.gov/26231772/]
- Our global food system is the primary driver of biodiversity loss [https://www.unep.org/news-and-stories/press-release/our-glob...]
https://en.wikipedia.org/wiki/Holocene_extinction
https://en.wikipedia.org/wiki/Planetary_boundaries#Nine_boun...
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.