As electrical engineers often do, the researchers in this study first used computer simulations of how the core aging circuit operates. This helped them design and test ideas before building or modifying the circuit in the cell. This approach has advantages in saving time and resources to identify effective pro-longevity strategies, compared to more traditional genetic strategies.
“This is the first time computationally guided synthetic biology and engineering principles were used to rationally redesign gene circuits and reprogram the aging process to effectively promote longevity,” said Hao.
Several years ago the multidisciplinary UC San Diego research team began studying the mechanisms behind cell aging, a complex biological process that underlies human longevity and many diseases. They discovered that cells follow a cascade of molecular changes through their entire lifespan until they eventually degenerate and die. But they noticed that cells of the same genetic material and within the same environment can travel along distinct aging routes. About half of the cells age through a gradual decline in the stability of DNA, where genetic information is stored. The other half ages along a path tied to the decline of mitochondria, the energy production units of cells.
The new synthetic biology achievement has the potential to reconfigure scientific approaches to age delay. Distinct from numerous chemical and genetic attempts to force cells into artificial states of “youth,” the new research provides evidence that slowing the ticks of the aging clock is possible by actively preventing cells from committing to a pre-destined path of decline and death, and the clock-like gene oscillators could be a universal system to achieve that.
“Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally-designed gene circuits that slow aging,” the researchers note in their study.