From the abstract of the paper, significantly more nuance.
> Despite persistent immune aging phenotypes, GzmK deficiency markedly attenuated organ aging, effectively uncoupling immune and tissue aging... These findings identify GzmK as a tissue-specific driver of organismal aging but not immune aging or systemic inflammaging.
Interestingly, their lifespans would probably be affected very little.
> GzmK does not affect steady-state immune aging or aged immune responses after challenge
Virtually all old mice die of cancer, especially in the lab. If GzmK doesn't mitigate immune system aging, GzmK-null mice are still going to die of cancer, for little or no change in lifespan. (But presumably an improved healthspan due to reduced soft tissue and bone aging.)
> Virtually all old mice die of cancer, especially in the lab. If GzmK doesn't mitigate immune system aging, GzmK-null mice are still going to die of cancer, for little or no change in lifespan.
Would introducing the cancer-reducing TP53 genes found in elephants[1][2] to mice help with this? Or would they likely just be too incompatible, with the species difference being too large?
> Virtually all old mice die of cancer, especially in the lab
Bret Weinstein did research on this topic which suggested that this is caused by lab mice having extraordinarily long telomeres which cause them to be good at cell repair but bad at limiting neoplasm growth due to delayed apoptosis. The result of this combination would be that lab tests on potential damage done by preparations on these mice is less valid 'cause they are better at repairing such damage than the average mammal due to those long telomeres. It also means nearly all these mice succumb to cancer. They're not normal mice, at all.
The reserve-capacity hypothesis: evolutionary origins and modern implications of the trade-off between tumor-suppression and tissue-repair
This paper examined captive wild mice, which they caught themselves on school grounds, and noted that "mice in both feeding groups died from various causes, chief among these a range of cancers":
No, even wild mice or rats are cancer magnets. If you have a pet rat, it will likely die of cancer.
This is a huge problem for medical research. Imagine that you conduct a safety test of your compound on mice, and 25% of the test group die of cancer within 1 year. That's bad, right? Well, the control group also has 20% cancer rate.
Humans have the same protein. Knock out studies in mice have historically been very informative about human biology (with some exceptions). That’s very different from drug studies, where the molecules not only have to have the same effect in the model species, but also all off target effects have to be similar. That’s a higher barrier to clear and why mice studies of pharmaceutical interventions should (and do) face higher scrutiny.
interesting, i exactly read the opposite position from biologists that the mice experiments are now very useful when it comes to applicability to humans. I guess we have every possible oppinion.
I don't think that any self-respecting biologist would actually make any sort of categorical dismissal of research in mice. That kind of research has been the basis of noble prize-winning advancements in immunotherapies that now positively impact cancer survival rates for humans.
I'm sure the totality of opinions from biologists is vast and complex, but there is no way that "all opinions have been expressed" is a faithful report of the state of our knowledge on biology.
The "in mice" meme needs to be retired. We share critical similarities in DNA, proteins, immune systems and immune responses that already have been the basis for impressive advances in research applicable to humans when it comes to immunotherapies.
We shouldn't overhype research done on mice but we also shouldn't reflexively dismiss it as unrelated to humans.
Paper: https://www.cell.com/immunity/fulltext/S1074-7613(26)00440-1
Granzyme K is the protein.
Granny Enzyme, you say?
Great, finally Leonardo DiCaprio will be able to find his life partner.
From the abstract of the paper, significantly more nuance.
> Despite persistent immune aging phenotypes, GzmK deficiency markedly attenuated organ aging, effectively uncoupling immune and tissue aging... These findings identify GzmK as a tissue-specific driver of organismal aging but not immune aging or systemic inflammaging.
Paywall
Thank God! Finally, mice that don't age!
Interestingly, their lifespans would probably be affected very little.
> GzmK does not affect steady-state immune aging or aged immune responses after challenge
Virtually all old mice die of cancer, especially in the lab. If GzmK doesn't mitigate immune system aging, GzmK-null mice are still going to die of cancer, for little or no change in lifespan. (But presumably an improved healthspan due to reduced soft tissue and bone aging.)
> Virtually all old mice die of cancer, especially in the lab. If GzmK doesn't mitigate immune system aging, GzmK-null mice are still going to die of cancer, for little or no change in lifespan.
Would introducing the cancer-reducing TP53 genes found in elephants[1][2] to mice help with this? Or would they likely just be too incompatible, with the species difference being too large?
[1] https://news.cancerresearchuk.org/2023/08/12/can-elephants-g...
[2] https://jamanetwork.com/journals/jama/fullarticle/2456041
> Virtually all old mice die of cancer, especially in the lab
Bret Weinstein did research on this topic which suggested that this is caused by lab mice having extraordinarily long telomeres which cause them to be good at cell repair but bad at limiting neoplasm growth due to delayed apoptosis. The result of this combination would be that lab tests on potential damage done by preparations on these mice is less valid 'cause they are better at repairing such damage than the average mammal due to those long telomeres. It also means nearly all these mice succumb to cancer. They're not normal mice, at all.
The reserve-capacity hypothesis: evolutionary origins and modern implications of the trade-off between tumor-suppression and tissue-repair
Bret S Weinstein 1 , Deborah Ciszek
https://pubmed.ncbi.nlm.nih.gov/11909679/
This paper examined captive wild mice, which they caught themselves on school grounds, and noted that "mice in both feeding groups died from various causes, chief among these a range of cancers":
> https://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2006...
So I think that even wild mice are prone to immune aging and cancer development.
> Virtually all old mice die of cancer, especially in the lab
Is this related to them being cloned? Did anyone try to get some random mice or is that too taboo?
No, even wild mice or rats are cancer magnets. If you have a pet rat, it will likely die of cancer.
This is a huge problem for medical research. Imagine that you conduct a safety test of your compound on mice, and 25% of the test group die of cancer within 1 year. That's bad, right? Well, the control group also has 20% cancer rate.
I’d unironically love to have a pet rat that lives longer than a few years.
A good idea for a startup might be a pet shop where you can buy all kinds of weird genetically altered mice! Or custom order!
https://www.jax.org/jax-mice-and-services/find-mice
maybe this is your joke, but we've actually done it many times, even reversed aging... only to find it doesnt work on humans.
Can't wait for this to escape in New York City. Ageless undying sewer rats - what a utopia haha.
In mice.
Humans have the same protein. Knock out studies in mice have historically been very informative about human biology (with some exceptions). That’s very different from drug studies, where the molecules not only have to have the same effect in the model species, but also all off target effects have to be similar. That’s a higher barrier to clear and why mice studies of pharmaceutical interventions should (and do) face higher scrutiny.
interesting, i exactly read the opposite position from biologists that the mice experiments are now very useful when it comes to applicability to humans. I guess we have every possible oppinion.
I don't think that any self-respecting biologist would actually make any sort of categorical dismissal of research in mice. That kind of research has been the basis of noble prize-winning advancements in immunotherapies that now positively impact cancer survival rates for humans.
I'm sure the totality of opinions from biologists is vast and complex, but there is no way that "all opinions have been expressed" is a faithful report of the state of our knowledge on biology.
The reasoning they gave seems plausible, what reasoning do your biologists give for holding the opposite position?
The "in mice" meme needs to be retired. We share critical similarities in DNA, proteins, immune systems and immune responses that already have been the basis for impressive advances in research applicable to humans when it comes to immunotherapies.
We shouldn't overhype research done on mice but we also shouldn't reflexively dismiss it as unrelated to humans.