Naked mole rats don’t age. Other mammals do. Therefore, whatever causes ageing must be hard but not impossible for evolution to stop. Here is one plausible hypothesis.
The environment of naked mole rats provides unusually strong evolutionary pressure against ageing. So transposon-killing RNAs are unusually prevalent. Every time a mutation breaks a transposon, that provides an advantage, the fewer transposons you start with, the slower you age. This selection is balanced by the fact that transposons occasionally manage to replicate, even in the gonads. In naked mole rats, that selection was unusually strong, and/or the transposons unusually unable to replicate. So evolution managed to drive the number of functioning transposons down to 0.
If naked mole rats have no functioning transposons, and animals that age do contain transposons, that would be strong evidence for transposon based ageing.
Of course, even if ageing is transposon based, evolution could have taken another route in mole rats. Maybe they have some really effective transposon suppressor of some kind.
I don’t know how hard this would be to test. Can you just download the mole rat DNA and put it into a pre-made transposon finder?
approximately 25% of the NMR genome was represented by transposon-derived repeats, which is lower than in other mammals (40% in human, 37% in mouse, and 35% in rat genomes)
However it’s just a 1⁄3 or so reduction compared to similar mammals, so on its own that doesn’t explain much. But it suggests a possible lead.
Most of “transposon-derived repeats” are essentially corpses of transposons that have mutations that make them nonfunctional. The thing that matters isn’t how much of the genome is due to transposon-derived repeats but how many active transposons there are.
Then for those transposons that are active it matters how easy they are to activate and whether there are mechanisms in somatic cells to silence them.
When it comes to the claim of immortal naked mole rats it’s worth keeping in mind that the oldest naked mole rat we know is 39 which is an age where even most humans don’t get cancer. It might be that naked mole rats do die at age 150 due to the few active transposons they have being able to cause problems by at age 150 we would still observe what we observe today about naked mole rats.
My guess would be transposon suppression rather than evolving away all of the transposons—upregulating existing repression mechanisms would be easier than removing every single active transposon copy. Though I’d still be interested in the test—even if suppression is the main mechanism, I’d still be interested to see how the number of transposons in naked mole rats compare to other rodents. (It is a nontrivial test to run, though—DNA sequencing is particularly unreliable when it comes to transposons, because there are so many near-copies.)
Alternatively, it’s also plausible that the naked mole rat’s defenses are elsewhere in the chain. In particular, they live in a low-oxygen environment, so it’s often speculated that they have very low ROS levels. If that’s the case, we’d still expect transposons to copy occasionally, but cellular-stress-events in which DNA is damaged by ROS, and transposons are temporarily less-repressed while the damage is repaired, would be much more rare.
I’ve seen this claim about naked mole rats thrown around a bunch but it’s left me with the question of what naked mole rats do die of? If their mortality likelihood truly doesn’t increase, we’d expect there to be some very long-lived naked mole rats. Is the issue just we haven’t held them in captivity for long enough to see them die of natural causes? I vaguely remember reading somewhere that eventually they stop eating or die in other ways but can’t seem to find the reference now.
In the lab, the cause of death is usually hard to find; the main issue that shows up in necropsies, Buffenstein said, are mouth sores, indicating the animals weren’t eating, drinking or producing saliva well in their last few days and infection set in.
“We really don’t know what’s killing them at this point,” Buffenstein said.
Naked mole rats don’t age. Other mammals do. Therefore, whatever causes ageing must be hard but not impossible for evolution to stop. Here is one plausible hypothesis.
The environment of naked mole rats provides unusually strong evolutionary pressure against ageing. So transposon-killing RNAs are unusually prevalent. Every time a mutation breaks a transposon, that provides an advantage, the fewer transposons you start with, the slower you age. This selection is balanced by the fact that transposons occasionally manage to replicate, even in the gonads. In naked mole rats, that selection was unusually strong, and/or the transposons unusually unable to replicate. So evolution managed to drive the number of functioning transposons down to 0.
If naked mole rats have no functioning transposons, and animals that age do contain transposons, that would be strong evidence for transposon based ageing.
Of course, even if ageing is transposon based, evolution could have taken another route in mole rats. Maybe they have some really effective transposon suppressor of some kind.
I don’t know how hard this would be to test. Can you just download the mole rat DNA and put it into a pre-made transposon finder?
This seems relevant: https://www.nature.com/articles/nature10533
However it’s just a 1⁄3 or so reduction compared to similar mammals, so on its own that doesn’t explain much. But it suggests a possible lead.
Most of “transposon-derived repeats” are essentially corpses of transposons that have mutations that make them nonfunctional. The thing that matters isn’t how much of the genome is due to transposon-derived repeats but how many active transposons there are.
Then for those transposons that are active it matters how easy they are to activate and whether there are mechanisms in somatic cells to silence them.
When it comes to the claim of immortal naked mole rats it’s worth keeping in mind that the oldest naked mole rat we know is 39 which is an age where even most humans don’t get cancer. It might be that naked mole rats do die at age 150 due to the few active transposons they have being able to cause problems by at age 150 we would still observe what we observe today about naked mole rats.
My guess would be transposon suppression rather than evolving away all of the transposons—upregulating existing repression mechanisms would be easier than removing every single active transposon copy. Though I’d still be interested in the test—even if suppression is the main mechanism, I’d still be interested to see how the number of transposons in naked mole rats compare to other rodents. (It is a nontrivial test to run, though—DNA sequencing is particularly unreliable when it comes to transposons, because there are so many near-copies.)
Alternatively, it’s also plausible that the naked mole rat’s defenses are elsewhere in the chain. In particular, they live in a low-oxygen environment, so it’s often speculated that they have very low ROS levels. If that’s the case, we’d still expect transposons to copy occasionally, but cellular-stress-events in which DNA is damaged by ROS, and transposons are temporarily less-repressed while the damage is repaired, would be much more rare.
I’ve seen this claim about naked mole rats thrown around a bunch but it’s left me with the question of what naked mole rats do die of? If their mortality likelihood truly doesn’t increase, we’d expect there to be some very long-lived naked mole rats. Is the issue just we haven’t held them in captivity for long enough to see them die of natural causes? I vaguely remember reading somewhere that eventually they stop eating or die in other ways but can’t seem to find the reference now.
From https://www.livescience.com/61568-naked-mole-rats-no-aging.html: