Genetic stability key to switching off ageing

Stabilising gene networks may switch off ageing, scientists have found in an advance that could create potential therapies against age-related diseases.
"In our work, we analysed the stability of a simple gene network model and found that gene networks describing most common species are inherently unstable," said Peter Fedichev, from Gero, a biotech company in Hong Kong that conducted the research in collaboration with Professor Robert J Shmookler Reis, one of the leading academics in the field of ageing.
"Over time, it undergoes exponential accumulation of gene regulation deviations leading to diseases and death. We conjectured, that the instability is the cause of ageing," said Fedichev.

"However, should the repair systems be sufficiently effective, the gene network can stabilise so that the damage to the gene regulation can remain constrained along with mortality of the organism," Fedichev said.
The stable case of genetic networks described by their model fits the negligible senescence phenomena. Negligibly senescent animals, such as naked mole rat, do not show signs of functional decline or any increase of mortality with age.
On the contrary, the mortality rate in humans, and in the most of the other species increases exponentially with age.

The reproductive, regenerative functions and stress-resistance decline during the process of ageing.

According to the model, the stability of gene network depends on a few major parameters such as effective gene network connectivity, "effective" genome size, proteome turnover and DNA repair rate.
The lifespan can be increased by tuning, or hacking any of these parameters.
This hypothesis is supported by the biological evidence, inferred either from evolutionary observations or from experiments.
For instance, it is examined how by protecting mitochondrial genes by their transfer to the nuclear genome, or by establishment of the nuclear envelope, the effective interactions between the genes and the cellular environment was substantially reduced.
These events led to the formation of multicellular life which in turn resulted in a dramatic increase in organisms complexity and life expectancy.

Experimental reduction of the network connectivity by silencing of kinase cascades involved in regulation of transcription factors leads to a dramatic effect on the lifespan in C elegans worms.
The relation between stresses, stress resistance and ageing demonstrate that damage to gene regulation from stresses encountered even at a very young age can persist for a very long time and influence lifespan.
Further research into the relation between gene network stability and ageing will make it possible to create entirely new therapies with potentially strong and lasting effect against age-related diseases and ageing itself, researchers said.
The study was published in the journal Scientific Reports.