Scientists from the University of Cologne and other scientific institutions led by Andreas Beyer (Andreas Beyer) found out the molecular cause of aging and managed to slow it down in experimental animals, as well as human cells. This may help in the invention of drugs that increase life expectancy, writes the journal Nature.
According to the publication, scientists were able to slow down the processes leading to aging in mice, rats, fruit flies, nematode worms and human cells. To do this, the mouse was put on a low-calorie diet, and the fly and the worm were genetically modified, thus reducing the rate of reading RNA from DNA. The aging mechanism turned out to be universal for all organisms participating in the experiment.
Aging at the molecular level, in particular, is manifested in the fact that the chromosomes become shorter due to the loss of terminal fragments. However, this is not the only molecular sign of aging. Beyer and colleagues found that another feature of an aging organism is that it reads RNA from DNA differently. The protein RNA polymerase II is responsible for this reading. In all these organisms, in old cells, this protein moves along the DNA faster and makes more mistakes, the authors of the study found. The scientists' idea was to slow down the movement of RNA polymerase II, and it worked.
In the case of fruit flies and nematode worms, scientists studied genetically modified organisms in which the reading speed was reduced due to mutation. As a result, life expectancy has increased by 10-20%. The mutant worms were then bred back into "normal" organisms (without the mutation) to check that there was a causal relationship. And their life expectancy, on the contrary, has decreased.
The scientists also found that in mice, worms and flies, in which the genes responsible for the insulin signaling system are damaged, RNA polymerase II moves more slowly. This is consistent with earlier studies that found that inhibition of insulin signals leads to increased lifespan in many animals. In addition, the low-calorie diet that scientists put mice on slowed down the movement of RNA polymerase II.
As for humans, experiments were carried out on cell cultures obtained from the umbilical vein and from the lungs. Scientists studied the dependence of the speed of movement of RNA polymerase II on the structural organization of DNA in cells. DNA in a cell is "wound" on a "frame" consisting of histone proteins, and form the structural parts of the chromosome - nucleosomes. In aging cells, the scientists found fewer nucleosomes and, as a result, RNA polymerase II moved faster along a smoother path. With an increase in the level of histone expression, RNA polymerase II slowed down its movement. In fruit flies, it has been shown that increased histone levels lead to a longer lifespan.
According to the study, the organisms involved in the experiment have the same universal mechanisms that affect lifespan, associated with the speed of RNA polymerase II. The behavior of RNA polymerase II could help develop drugs that aim to slow down human aging.