The scientific team of a new biotech company Gero in collaboration with one of the leading academics in the field of aging Prof. Robert J. Shmookler Reis (current world record holder in life extension for model animals - 10 fold for nematodes) has recently brought new insights into biology of aging and age-related diseases, primarily, around the stability and stress resistance of certain gene regulatory networks. The work has just been published as “Stability analysis of a model gene network links aging, stress resistance, and negligible senescence” in Scientific Reports (Nature Publishing group).
“In our work, we analyzed the stability of a simple gene network model and found that gene networks describing most common species are inherently unstable. Over time, it undergoes exponential accumulation of gene regulation deviations leading to diseases and death. We conjectured, that the instability is the cause of aging. However, should the repair systems be sufficiently effective, the gene network can stabilize so that the damage to the gene regulation can remain constrained along with mortality of the organism.” - says Dr. Peter Fedichev, Gero CSO.
The stable case of genetic networks described by their model fits the negligible senescence phenomena. It’s well known that negligibly senescent animals, such as naked mole rat, do not show signs of functional decline or any increase of mortality with age. The tissues of these species are exceptionally stress-resistant.
On the contrary, the mortality rate in humans, and in the most of the other known species increases exponentially with age. The reproductive, regenerative functions and stress-resistance decline during the process of aging. These are the manifestations of the underlying gene network instability.
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 various experiments performed by the leading scientists that have significantly extended life expectancy. For instance, it’s 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 are considered the major factors that led to the formation of multicellular life which in its 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 (up to a 10x lifespan extension by a single mutation). The relation between stresses, stress resistance and aging is analyzed and 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. That is why we believe that further research into the relation between gene network stability and aging will make it possible to create entirely new therapies with potentially strong and lasting effect against age-related diseases and aging itself.
The work has just been published as “Stability analysis of a model gene network links aging, stress resistance, and negligible senescence” in Scientific Reports (Nature Publishing group). http://www.nature.com/articles/srep13589
Gero is a drug discovery company designing first in class small molecule therapeutics using proprietary, industry-leading molecular modeling and systems biology technologies. The company provides answers to the challenges of human anti-aging therapies development that consists of two components: therapeutic targets identification and drug candidates development.
Gero is a team of experts from diverse fields of studies - theoretical physics, drug discovery and development, and IT business. The scientific effort is led by Peter Fedichev, Ph.D, CSO, a former condensed matter physicist, and an international group of biologists, medicinal chemists and computer science experts. Over a few last years Gero developed a series of increasingly sophisticated aging models meeting practical requirements for a successful design, clinical trial and therapeutic application of future anti-aging drugs. Gero team works to improve fundamental theoretical understanding of aging using cross-disciplinary approaches and borrowing from theoretical physics and biology. The company also has in-house drug development expertise so that the complete geroprotector candidate production cycle can be performed.