As our cells age they progressively become damaged by the oxidative process of life. DNA, the molecule that stores instructions for building the cell, is very sensitive to this damage, and when enough of it occurs the cell either becomes incapable of further dividing or becomes cancerous.
There are robust DNA repair networks in the cells which function to detect and repair this damage as it occurs.
In the current study researchers made the surprising finding that cells with more DNA damage live longer. They observed that cells lacking the enzyme that repairs the DNA base guanine lived longer than cells with the enzyme.
What they discovered is that when guanine is damaged by oxygen it turns into a molecule called 8-oxoguanine. This compound in turn is removed by a DNA repair molecule called OGG1. When the oxidized guanine is excised and replaced by normal guanine the 8-oxoguanine becomes bound the OGG-1. This new complex is a powerful signaling mechanism that activates what is known as the ras enzyme system.
“Ras family proteins are involved in almost every cell function: metabolism, activation of genes, growth signals, inflammation signals, apoptosis,” said lead author Istvan Boldogh. “Because it activates Ras pathways, the release of 8-oxoguanine in DNA base repair could be a master regulator of many very basic processes.”
Thus the damaging event itself turns on the process which restores and maintains cellular health.
“The ability to regulate 8-oxoguanine excision may give us the ability to prevent the inflammation that’s key to a number of chronic diseases — arthritis, atherosclerosis, Alzheimer’s and others,” said Boldogh. “We believe it may even enable us to extend lifespan, or at least healthy lifespan, which would be a very big achievement. Possibilities like that make us believe that this discovery is going to be very significant.”