When we get old, the Pancreas Re-programs itself to Poison us with Sugar

In an article in today’s Science Times, Amanda Schaffer reviews findings by Chutima Talchai and Dr. Domenico Accili at Columbia concerning the fate of insulin-producing “islet” cells in the pancreas.

One big and nearly universal manifestation of aging is that our sugar metabolism becomes less responsive to insulin. Insulin signaling is a cry of “enough!” to the liver, and in response to insulin, the liver is supposed to cease dumping sugar (fuel) into the blood stream. When the system loses sensitivity to insulin, the body begins to poison itself with sugar, which can result in heart disease, nerve damage in the extremities, and loss of vision – all hallmarks of Type 2 Diabetes.

For a while, the pancreas tries to compensate by pumping more insulin. But then the pancreatic cells poop out.

“We used to say that the beta cells poop out,” said Alan Saltiel, director of the Life Sciences Institute at the University of Michigan. In reality, he added, this shorthand meant “we have no idea what’s going on.”

From the perspective of this blogger, it’s very clear what’s going on: the body is poisoning itself with sugar. In order to insure suicide on a schedule, our bodies come with multiple, redundant programs of self-destruction as “standard equipment”.

The primary purpose of the fixed life span is an aid to population stabilization. Aging brings death under control of the genome, so that the population can avoid unrestrained growth which leads inevitably to overshoot and population crashes, risking extinction. Without aging, deaths would be very “lumpy”. When there’s an epidemic, everybody is dying at once; otherwise practically no one is dying. When there’s a famine, the whole population goes down at once; when food is available, the population just keeps expanding until there is a famine. This is no way to run an ecosystem! In fact, it’s a recipe for any species to trash its own ecosystem, risking extinction.

This evolutionary theory explains why overeating triggers diabetes earlier.  It’s a signal to the body that there is plenty of food, certainly no famine in sight, and the death rate from hunger is probably pretty low.  The death rate from aging is programmed to complement death from starvation, so when the latter is low, the former is elevated.

What Schaffer and Talchai have found is that the insulin-producing islet cells don’t wear out. Rather they regress to an earlier stage in their development, in which they cannot produce insulin. This happens as a result of gene expression.

Every cell in your body has exactly the same genes as every other cell. But in any given cell, most of the genes are covered up by histones, and inactive. It is the choice of which genes are active that determines the cell’s morphology and function. Gene expression separates a bone cell from a nerve or muscle cell. Gene expression also can vary over time. It is gene expression that distinguishes an old cell from a young cell.

If islet cells are “stepping back in time”, then this is certainly a process under genetic control. You might still talk about it as something that has “gone wrong” if you’re wedded to the idea that programmed aging cannot, as a matter of theory, be a purposeful adaptation. But if you’re an adaptationist (like me) it seems natural to see this regression as part and parcel of the aging program.

“In Dr. Accili’s research, some of the progenitor cells went on to produce another hormone, glucagon, which acts to raise blood sugar.”

In other words, the islet cells are not just pooping out, they are actually pouring gasoline on the aging fires! They become active agents of self-destruction. Do you still think this is just a random “disregulation”? Looks like an aging program to me!

“If something similar occurs in humans with Type 2 diabetes, scientists may find ways to nudge de-differentiated beta cells to return to their mature, insulin-producing form.”

Yes, “programmed aging” is a very hopeful perspective! If the body is not wearing out, if aging is merely a matter of signaling, then we can hope to modify nature’s signals and stop aging in its tracks!