The proposal of a prize for extending the lifespan of insects suggests lack of awareness of the processes involved in aging and how evolution goes about producing compensations for or solutions to these processes.
Prometheus will have a field day with that statement...
Before Prometheus gets here, I'll throw in my two cents on the rest of your post
Insects are composed of post-replicative cells and do not get cancer.
I said the
same thing, and Dr. de Grey seemed to back this statement up to some extent a few days ago, though I don't remember exactly what he said.
Unfortunately, recent research has indicated that although aging may look superficially the same in varied species, the exact mechanisms that the gene profiles are designed to attack can be different. An obvious example is that flies and yeast don't get cancer.
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Aging is very complex. We understand it very little. Yet there is much evidence that aging is more than just evolution's disregard for organisms once they have reproduced. There is strong evidence that multiple aspects of aging are tied to preventing cancer.
However, I'm wondering if there are species we can use with shorter lifespans than mice, but that still get cancer. It is my opinion (based loosely on studies I've read) that cancer is intertwined with aging in humans. Extending the lifespan of a species that doesn't get cancer won't convince me.
This hasn't bothered me as much in recent weeks. While insects and chordates diverged a very long time ago, there are still several mechanisms that are preserved. That resveratrol can have the same impact on yeast, worms, and flies, and anecdotally in humans, implies that such a mechanism evolved before the eukaryots split--before the animal kingdom existed, and certainly before insects diverged from chordates.
Other mechanisms will have evolved after the split from insects, to deal with the likes of cancer.
But we must ask ourselves why we age. Is it a mechanism to prevent and fight cancer, as some evidence suggests? Why, when flies and yeast don't get cancer, do they age? And why are many of the same age-related problems seen: DNA, RNA, and protein damage, etc.? Why are these problems relevant on the timescales of these organism's lifetimes, when in the same block of time the amount of damage accumulated in us is practically negligible?
While certain aspects of aging seem tied to our cells' inability to fix DNA damage as fast as it occurs, why is it that a fruit fly doesn't have the repair capabilities that a human has? Why couldn't a fruit fly live as long as a human? Or at least as long as a mouse? Why couldn't a mouse live as long as a human? Why can't a human live as long as, well, Methuselah? At the structural level, there are differences, but at the cellular level, it's still the same stuff: proteins, DNA, RNA, lysosomes, and mitochondria, all dancing their chemical dance.
Creating a fly that lives a year will NOT be irrelevant at all. It shows that it is possible to remove what evolution most probably designed into us--a species-appropriate time-bomb--whether we want to accept that or not. And the techniques will probably be well enough preserved, since aging itself seems to predate the split of eukaryots.
Far better to study the genomes of long lived mammals which evolved independent longevity assurance programs such as elephants and whales.
Once we know which genes and specific *mechanisms* to target (I'm talking more than the broad mechanisms such as DNA repair, antioxidant production, or growth hormone/receptor interplay), we could use the
relevant genes from the long-lived species to get an idea of what genes to transfect humans with, or at least how to modify our own genes. But we don't even know which mechanisms are the culprits! We have a few prime suspects, but none of it is definitive. It's one thing to know that mitochondrial ROS production can cause DNA damage, and that DNA damage is "bad", but it's quite another thing to actually have definitive proof that mtROS production *causes* senescence. Proof is beginning to emerge in recent and on-going studies, but like I said, just theorizing a connection didn't make it correct. There is bound to be more than just this one mechanism at work, since many anti-oxidants don't affect mtROS, and yet they have positive health benefits (squaring the survival curve if not lengthening it).
Experimenting on long-lived species is pointless. It will take forever. It's how the experiments are run: once gene at a time. "Let's see what happens when we damage this gene; when we deactivate it (one or both copies); when we down-regulate it; when we up-regulate it. Great, that gene's done, let's try this one. Let's catalog this indivudal gene's effects on this protein level, and that protein level, and this chemical process, and that chemical process. Now let's try it all over again, in this species, and see how it's different, and how it's the same. Okay, now in this species."
Microarrays help, because they limit the number of genes we have to check (since we certainly don't have time to test tens of thousands per species). But it's still an
in vitro process. Verifying a gene
in vivo is still done one gene at a time.
It's all in the pursuit of pure science. And one day, many decades from now (actually, it would take centuries if not millenia at the current rate, but I'm taking into account the increasing technology over the next few decades), we'll understand enough about how long-lived species get done what the shorter-lived species cannot, to start tinkering with aging in humans.
There are other species ranging from amphibians or reptiles which can regrow body components and plants such as sequoias that can retain functional genomes within the organism for thousands of years. These have much more to teach us than the study of insects.
If I only cared about curing aging by the end of the century, or at the earliest by the middle of it, then yes, I agree with that statement. I'm only 26, so I've got the time.
With short-lived species, on the other hand, we can test not only the chemical interactions (and then theorize about the effects on lifespan), but we can also test the actual lifespan. And we can test multiple genes at once and not worry about not understanding in painstaking detail the exact mechanisms at work (where such painstaking detail would otherwise be required to theorize the effects on a lifespan we cannot test). With two or three more experiments, we can refine our multi-gene approach, and get better results. Now we've got our result (which is still far from perfect, but far exceeds the current results), and we've shown the world that it was possible. And we identified candidate mechanisms (and in many cases, candidate
genes), that the mouse researchers, who are still on their first batch of mice (and hence many generations behind), can try in the second batch.
Besides, even if using long-lived species is the way to go, we could not possibly hope to sponsor a prize or other such foundation/society to promote the research of the wide variety of long-lived species. Such is well beyond the realm of the Immortality Institute or the Methuselah Foundation. Such is the responsibility of the greater gerontology/biology community itself; this is more a matter of a public relations battle, *political* battles, with insiders hopefully being able to help by orchestrating such changes in the general research policies. If you're in a position to make policy decisions like this, or to influence said decisions, then by all means, do it.
But the gerontology community isn't budging. That's the very reason that Dr. de Grey and Dave Gobel co-founded the Methuselah Foundation and created the Methuselah Mouse Prize: Because we can affect PR, not only through spreading information (which the MF website does, as does Dr. de Grey's website), but also by spurring research. Focused research. One species. One goal (with two subgoals). Relatively short timeframe. Simple rules. Winner-takes-all publicity, though the prize money is aportioned based on how well you achieved the goal, relative to the previous winner.
We want to put the gerontology community in a position where they can come out and say, "Yes, we know we can slow aging drastically, and perhaps even reverse it, and we can do it in a couple decades." Those in the gerontology community who don't believe this will increasingly be put on the spot in the face of mounting evidence that species after species is having its maximum lifespan dramatically extended, by factors of 2 and 3 and more for even closely related species such as mice.
The Methuselah Mouse Prize seeks to bring that day sooner, perhaps decades sooner. But that day is still years away, and possibly even a decade away or more. A fly prize can bring that day years sooner still. Even if we have doubts about whether flies will be relevant, it will cost pennies on the dollar to get substantially better life extensions. And genes and specific mechanisms WILL BE found that will apply in at least some (and more probably in most) cases to mice, which will accelerate progress in the Methuselah Mouse Prize, and bring years sooner the day that gerontologists will no longer be able to say that curing aging is not possible.
But going back to your contention of using long-lived species: even if studying long-lived species will ultimately yield the best results, the easiest way for you and me to make that *huge* project a reality is to force the gerontologists into it, and creating a public outcry for faster research into aging is probably the easiest way make that happen. Despite the public's pessimism, I can't help but think that seeing an 8-year-old non-dwarf, non-CR'd mouse will create just such an outcry. A six-year-old mouse might even do the trick.
And if a 9-month-old fly, or a 13-month-old fly, is what it takes to get an 8-year-old mouse, which is what it takes to create the clichéd Apollo-Moon-Project-equivalent for curing aging, then I'm all in.
Jay Fox
), etc. But for strictly germline genetic alterations, this approach is valid, though potentially slow (but only as slow as the reported lifespan!).
