Cellular reprogramming in DNA damage mediated aging

Cellular reprogramming in DNA damage mediated aging


The heredity substance DNA is the blueprint of our life. Like an instruction manual it contains all the information needed for cells and the body to function properly. In the process, the DNA is always exposed to threats like UV light, pollutants and damage by metabolic byproducts. Many of those damages can be undone by sophisticated repair mechanisms. Nevertheless, the accumulation of DNA damage is a cause of aging. A team of scientists is now trying to better understand the damage to the genome driving the aging process.

For the study published in the journal Cell Reports, the researchers examined the nematode Caenorhabditis elegans. Because of its short life span of only twenty to thirty days, the worm is a popular model organism for aging research. When they exposed one-day-old worms to DNA damaging UV light, the team found that the young animals show surprising similarity to worms at old age.

They compared comprehensively proteins, fatty acids, metabolism and signaling pathways. For scientists, the aha moment was when they found that the changes they knew to be occurring in old worms were now already unfolding in the young individuals within hours of inflicting the DNA damage. 'Everything was there, nearly the complete picture of the aging process. That way, we could show that the aged individuals re-program their biological processes in reaction to the increased damage in their DNA.

In total, more than 5,000 different proteins and their connection via signaling pathways were examined: How are they connected, how are they interacting, do they regulate the same process? Like in a crossword puzzle, connections between metabolism, preservation of the DNA and proteins and signaling pathways determining the aging process became apparent.

Authors saw metabolic changes indicative of a tissue maintenance program and implicate an autophagy-mediated proteostatic response. They assign central roles for the insulin-, EGF-, and AMPK-like signaling pathways in orchestrating the adaptive response to DNA damage

'In the end, we found all the strings and junctions - that was impressive and even better than expected. What was looming in other studies could be shown by us in the whole picture', the researcher says.

Even though worm and human do not appear all that similar at first glance, their cellular processes are very similar and comparable. Many signalling pathways are identical, the metabolism alike, the quality control of the proteins are similar. That is what makes the worm so relevant for aging research.

In the next step, the researchers want to take a closer look at the signalling pathways. The aim is to better understand the effects of DNA damage on the organism and to make healthy aging possible for humans.