Heterochromatin Levels in Flies Can Raise and Lower Lifespan
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Heterochromatin is the name given to the more tightly packaged structural forms of DNA and proteins found in the cell nucleus. It has been shown to be involved in cellular senescence, and is a part of the way in which genes are turned on or off, but like most things in the nucleus it is also involved in the deep, dark depths of many other mechanisms - down there in the basement clockwork of the tall towers of machinery that run a cell. Modern day research tools are making it ever easier to catalog the cogs, gears, and operations that take place on any one level of one particular machine-tower, but it is still very hard and time-consuming to turn localized, disconnected understandings into realizations about the mechanism as a whole.

So researchers can presently say a great deal about heterochromatin and its localized behavior, but far less about how these descriptions of structure and low-level operations relate to higher level cellular mechanisms, and never mind how that all ties into trajectories of health and longevity for organisms as a whole. Cells are complicated, exceedingly so, and as a consequence the life sciences are at a point of simultaneously drowning in data while being unable to answer even a tiny fraction of all the questions about biology that are presently asked. This won't last, given the pace of progress in computational technologies, but it is rather like the prospect of starving amidst plenty for the near future.

You might recall that - in my opinion - the acid test as to whether a biological mechanism is interesting to those us who follow longevity science is not whether you can use it to shorten life span, but rather whether you can use it to extend health life. Even better is a case in which researchers can demonstrate both of those goals: turn the dial one way and life shortens, turn it the other and it lengthens - these are indications that there might be something worthy of further investigation in that research.

That all said, here is a demonstration that heterochromatin levels in flies can be used to dial lifespan up and down:

To understand the role of heterochromatin in animal aging, and the underlying molecular mechanisms, we altered heterochromatin levels in Drosophila by genetically manipulating Heterochromatin Protein 1 (HP1) levels ... we examined the life spans of flies with reduced or increased levels of HP1. These flies exhibit reduced or increased levels of heterochromatin, respectively, during development, as HP1 is an integral component of heterochromatin and controls heterochromatin levels.

We found that reducing HP1 levels by half [caused] a dramatic shortening of life span compared to isogenic controls. ... Conversely, a moderate overexpression of HP1, caused by basal activity of the hsp70 promoter, significantly extended life span, resulting in a 23% increase in median life span and a 12% increase in maximum life span. Similarly, at non-heat shock conditions (25°C), a second (independent) line of hsp70-HP1 flies also lived significantly longer than their control flies.


These results suggest that heterochromatin levels significantly influence life span, and moderately higher levels of heterochromatin promote longevity.

Too much boosting of heterochromatin via the methods the researchers used is fatal to flies, unfortunately. The full paper offers some thoughts on the potential mechanisms of increased longevity with increased heterochromatin levels, but there is no definitive line item to point to - at this stage, only plausible hypotheses about cellular integrity, a slower rate of decline in muscle strength, and so forth.

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