My impression is that DNA repair mechanisms get dramatically less effective with age, and that piRNA and siRNA (and other such transposon repression mechanisms) are effective but not 100% effective even in germ cells. Since germ cells in males continue to divide through the entire lifespan, my naive expectation would be that the children of very old men to age faster than the children of younger men (not just “have worse health outcomes in general” but specifically “express the specific marks of senescence earlier”).
Is that a valid prediction of the “transposons make more transposons and eventually the exponential increase in the number of transposons kills the cell” hypothesis?
Since germ cells in males continue to divide through the entire lifespan, my naive expectation would be that the children of very old men to age faster than the children of younger men (not just “have worse health outcomes in general” but specifically “express the specific marks of senescence earlier”).
Yes, but likely a few days or months and not years.
Let’s think through a scenario.
Imagine that each human has 100 active transposons. Then imagine each additional transposon reduces the amount of raised children by 0.01. If left alone this process would reduce the active transposon count to zero. If we assume the amount of transposons that exists is in equilibirum, the amount of new transposons produced in the germline because the transposon suppression systems aren’t perfect, is exactly the amount that’s needed to keep the active transposon count on average at 100 active transposons.
Given that most of the effect of aging happen a lot later then when humans get children, it would be surprising to me when a single additional transposon would reduce the amount of raised children by 0.01. I haven’t run the numbers myself but I wouldn’t be surprised if on average there’s only one or less additional transposon per generation (at normal childbearing age).
If transposons don’t produce aging you also need to present a different mechanism of how increased transposon count produces a problem that’s big enough for evolution to keep the amount of transposons at their current level. I can’t think of a different mechanism of how transposons create the evolutionary pressure to keep their numbers in check in a organism like humans where there seems to be more transposon activity in non-germline cells.
My impression is that DNA repair mechanisms get dramatically less effective with age, and that piRNA and siRNA (and other such transposon repression mechanisms) are effective but not 100% effective even in germ cells. Since germ cells in males continue to divide through the entire lifespan, my naive expectation would be that the children of very old men to age faster than the children of younger men (not just “have worse health outcomes in general” but specifically “express the specific marks of senescence earlier”).
Is that a valid prediction of the “transposons make more transposons and eventually the exponential increase in the number of transposons kills the cell” hypothesis?
Yes, but likely a few days or months and not years.
Let’s think through a scenario.
Imagine that each human has 100 active transposons. Then imagine each additional transposon reduces the amount of raised children by 0.01. If left alone this process would reduce the active transposon count to zero. If we assume the amount of transposons that exists is in equilibirum, the amount of new transposons produced in the germline because the transposon suppression systems aren’t perfect, is exactly the amount that’s needed to keep the active transposon count on average at 100 active transposons.
Given that most of the effect of aging happen a lot later then when humans get children, it would be surprising to me when a single additional transposon would reduce the amount of raised children by 0.01. I haven’t run the numbers myself but I wouldn’t be surprised if on average there’s only one or less additional transposon per generation (at normal childbearing age).
If transposons don’t produce aging you also need to present a different mechanism of how increased transposon count produces a problem that’s big enough for evolution to keep the amount of transposons at their current level. I can’t think of a different mechanism of how transposons create the evolutionary pressure to keep their numbers in check in a organism like humans where there seems to be more transposon activity in non-germline cells.