The most recent posts related to progeria diseases remind me again that when it comes to aging we seem to be dealing with different areas of a very large jigsaw puzzle where most of the pieces between the areas are still missing. The best we can do is assemble different portions of the puzzle without worrying too much about how the portions will eventually fit together. As we build those portions we find they have irregular shapes with holes in them where smaller collections of pieces are still missing. We may have put together a portion of the puzzle and not know what it means – is the blue area sky, water or the side of a building? Is the accumulation of progerin in cells with aging just another irrelevant buildup of a substance in cells with aging, a major cause of other aging effects, or what? As we proceed we constantly keep looking for how one portion of the puzzle might be joined with another. Being able to join up two major portions is a breakthrough event. As time progresses a more and more coherent pattern emerges and the job gets easier. If you have ever worked on a very large jigsaw puzzle you know what I mean.
There are differences between the two kinds of puzzles, however. You know what an assembled jigsaw puzzle looks like because the image is printed on the top of the box. This image gives important color clues for putting the puzzle together. And you know you the box should contain exactly the pieces you will need. You know the pieces are accurately cut. It might take a week off-and-on to finish a 3000 piece jigsaw puzzle but the job is finite.
For the longevity puzzle we don’t know what the puzzle will look like when it is finished. We have to be constantly fishing around in the world literature to find new pieces. And some of the new pieces we find may be inaccurately shaped even if at first they seem to fit with some other pieces. What works in a mouse study may not apply to humans. If we put together a part of the puzzle with inaccurately shaped pieces that part won’t fit in with the rest of the puzzle and will eventually have to be taken apart and built over. At any point, we don’t know how many pieces are still missing, and we don’t know whether we will live long enough to find them all. So, the longevity puzzle is open-ended and might take 5 years or a lifetime before the picture is reasonably clear. What fun!