Lifespan: The Revolutionary Science of Why We Age—and Why We Don't Have To

by David A. Sinclair

Every time there’s a radical adjustment to the epigenome, say, after DNA damage from the sun or an X-ray, the marbles are jostled—envision a small earthquake that ever so slightly changes the map. Over time, with repeated earthquakes and erosion of the mountains, the marbles are moved up the sides of the slope, toward a new valley. A cell’s identity changes. A skin cell starts behaving differently, turning on genes that were shut off in the womb and were meant to stay off. Now it is 90 percent a skin cell and 10 percent other cell types, all mixed up, with properties of neurons and kidney cells. The cell becomes inept at the things skin cells must do, such as making hair, keeping the skin supple, and healing when injured. In my lab we say the cell has ex-differentiated. Each cell is succumbing to epigenetic noise. The tissue made up of thousands of cells is becoming a melange, a medley, a miscellaneous set of cells. As you’ll recall, the epigenome is inherently unstable because it is analog information—based on an infinite number of possible values—and thus it’s difficult to prevent the accumulation of noise and nearly impossible to duplicate without some information loss. The earthquakes are a fact of life. The landscape is always changing.

Information loss