It would be great if the mouse results turn out to apply to humans as well, but I have my doubts. These doubts are based on what I thought were pretty conventional biological assumptions, but that nevertheless don’t seem to be addressed in the anti-aging discussions I’ve seen.
The basic problem is that there’s a good reason mice don’t live long. Even if they didn’t age, the environment in which they live means they are very likely to die in a few years from starvation or predation. So genes that keep them from aging won’t be selected for because of either or both of two reasons: (1) The selective advantage of not aging, when you’re likely to die young anyway, isn’t enough to overcome random mutation that undoes the anti-aging genes. (2) The advantage of not aging comes at some (possibly rather small) cost in terms of increased likelihood of death from predation or starvation, or decreased fecundity early in life. (For instance, it might have an energy/food cost, or might come with decreased physical performance, such as in running speed.)
Humans live in a different environment, in which slower aging is more advantageous. And indeed humans age much slower than mice, presumably because we have genes that enable various anti-aging strategies that mice lack.
So, when a drug is found to slow aging in mice, the first question in my mind would be, “is this drug enabling a mechanism that is alreadypresent in humans?”.
And the default answer to this question would seem to be “yes”. If there’s some simple biochemical way of slowing aging, why don’t humans already have this, given that slower aging in humans would give a significant selective advantage? (Even (especially?) in pre-civilizational societies, significant numbers of people die of old age rather than from violence or starvation.)
On this reasoning, one would expect that a successful anti-aging program would have to involve something complicated, not easily produced by evolution. Something like, for example, nanobots inspecting cells for damaged DNA (comparing against a consensus sequence derived from a large number of the person’s cells), and killing cells that are too damaged. Or at least, if there is some relatively simple intervention that helps, one would expect it to be sufficiently subtle that it doesn’t show up in mice (but only after decades of life, when selective pressure for it in humans is comparatively small).
You are correct that interventions in mice do not always translate well to humans. Fortunately, several human trials have already shown that aging can be reversed. Time will tell how many of the current anti-aging approaches that have worked in mice will translate to humans.
The basic problem is that there’s a good reason mice don’t live long. Even if they didn’t age, the environment in which they live means they are very likely to die in a few years from starvation or predation. So genes that keep them from aging won’t be selected for because of either or both of two reasons: (1) The selective advantage of not aging, when you’re likely to die young anyway, isn’t enough to overcome random mutation that undoes the anti-aging genes. (2) The advantage of not aging comes at some (possibly rather small) cost in terms of increased likelihood of death from predation or starvation, or decreased fecundity early in life. (For instance, it might have an energy/food cost, or might come with decreased physical performance, such as in running speed.)
Humans live in a different environment, in which slower aging is more advantageous. And indeed humans age much slower than mice, presumably because we have genes that enable various anti-aging strategies that mice lack.
This comment doesn’t make a lot of sense to me since mice used in the lab for lifespan studies are not subject to evolution today—rather, specific strains used for different kinds of experiments are purchased from specialized laboratories, where they are selectively bred.
So, when a drug is found to slow aging in mice, the first question in my mind would be, “is this drug enabling a mechanism that is alreadypresent in humans?”.
And the default answer to this question would seem to be “yes”. If there’s some simple biochemical way of slowing aging, why don’t humans already have this, given that slower aging in humans would give a significant selective advantage? (Even (especially?) in pre-civilizational societies, significant numbers of people die of old age rather than from violence or starvation.)
Senescent cells by definition are apoptosis-resistant, meaning they are resisting the mechanisms (found in both mice and humans) to remove them. Hence, senolytic drugs extend lifespan in mice and probably humans by removing these cells, since the machinery in the body is unable to.
On this reasoning, one would expect that a successful anti-aging program would have to involve something complicated, not easily produced by evolution. Something like, for example, nanobots inspecting cells for damaged DNA (comparing against a consensus sequence derived from a large number of the person’s cells), and killing cells that are too damaged. Or at least, if there is some relatively simple intervention that helps, one would expect it to be sufficiently subtle that it doesn’t show up in mice (but only after decades of life, when selective pressure for it in humans is comparatively small).
I suggest you learn more about the field by watching some talks on YouTube by David Sinclair, Brian Kennedy, Judith Campisi, Aubrey de Grey, Nir Barzilai, Joao Pedro de Magalhaes or any other of the speakers here to give you a better idea of the field of research.
It would be great if the mouse results turn out to apply to humans as well, but I have my doubts. These doubts are based on what I thought were pretty conventional biological assumptions, but that nevertheless don’t seem to be addressed in the anti-aging discussions I’ve seen.
The basic problem is that there’s a good reason mice don’t live long. Even if they didn’t age, the environment in which they live means they are very likely to die in a few years from starvation or predation. So genes that keep them from aging won’t be selected for because of either or both of two reasons: (1) The selective advantage of not aging, when you’re likely to die young anyway, isn’t enough to overcome random mutation that undoes the anti-aging genes. (2) The advantage of not aging comes at some (possibly rather small) cost in terms of increased likelihood of death from predation or starvation, or decreased fecundity early in life. (For instance, it might have an energy/food cost, or might come with decreased physical performance, such as in running speed.)
Humans live in a different environment, in which slower aging is more advantageous. And indeed humans age much slower than mice, presumably because we have genes that enable various anti-aging strategies that mice lack.
So, when a drug is found to slow aging in mice, the first question in my mind would be, “is this drug enabling a mechanism that is already present in humans?”.
And the default answer to this question would seem to be “yes”. If there’s some simple biochemical way of slowing aging, why don’t humans already have this, given that slower aging in humans would give a significant selective advantage? (Even (especially?) in pre-civilizational societies, significant numbers of people die of old age rather than from violence or starvation.)
On this reasoning, one would expect that a successful anti-aging program would have to involve something complicated, not easily produced by evolution. Something like, for example, nanobots inspecting cells for damaged DNA (comparing against a consensus sequence derived from a large number of the person’s cells), and killing cells that are too damaged. Or at least, if there is some relatively simple intervention that helps, one would expect it to be sufficiently subtle that it doesn’t show up in mice (but only after decades of life, when selective pressure for it in humans is comparatively small).
You are correct that interventions in mice do not always translate well to humans. Fortunately, several human trials have already shown that aging can be reversed. Time will tell how many of the current anti-aging approaches that have worked in mice will translate to humans.
This comment doesn’t make a lot of sense to me since mice used in the lab for lifespan studies are not subject to evolution today—rather, specific strains used for different kinds of experiments are purchased from specialized laboratories, where they are selectively bred.
I don’t agree with this. Senescent cells (one of the 9 hallmarks of aging) for example accumulate both in humans and mice with older age, and contribute to age-related tissue and organ dysfunction in both.
Senescent cells by definition are apoptosis-resistant, meaning they are resisting the mechanisms (found in both mice and humans) to remove them. Hence, senolytic drugs extend lifespan in mice and probably humans by removing these cells, since the machinery in the body is unable to.
Following on from my previous comment, your comment here is not true. The most promising strategy to slowing aging is not overly complicated in principle, even though it is a technical challenge—it simply involves routinely repairing the damage associated with the hallmarks of aging as they emerge. This can be done even if the precise causes of that damage (from normal metabolism) are not known.
I suggest you learn more about the field by watching some talks on YouTube by David Sinclair, Brian Kennedy, Judith Campisi, Aubrey de Grey, Nir Barzilai, Joao Pedro de Magalhaes or any other of the speakers here to give you a better idea of the field of research.