December 6, 2023

Scientists at UC San Diego have developed a way to potentially slow the cellular aging process using an oscillating genetic “clock.” In tests, yeast cells were found to live significantly longer than cells without yeast cells.

The familiar symptoms of aging we all dread begin at the cellular level. Each of our trillions of cells undergoes a cascade of molecular changes during their lifetime, sustaining different types of damage, until eventually they can no longer function effectively and die. This can lead to age-related health declines, from wrinkles and gray hair to an increased risk of many diseases.

In a previous study, the UC San Diego team found that cells appear to age through one of two specific processes, choosing one path rather than deviating from the other. This split is roughly 50/50, even among cells from the same genetic lineage in the same environment. One pathway involves a decline in DNA stability, and the other involves a decline in mitochondria, which produce energy for cells. Either way, the end result is the same — cell death.

For the new study, the team developed a way to slow down cellular aging by allowing cells to oscillate between these two different processes. Continuing the path analogy, if you follow a path all the way to the end, you will get to your final destination (cell death) faster, but if you run back and forth between two paths, it will take longer.

To achieve this, the team rewired a central gene regulatory circuit that controls cellular aging. Normally it works like a toggle switch, sending certain cells down certain pathways, but in this case, the researchers tuned it to act as a genetic oscillator. This triggers the cell to periodically switch from one pathway to the other, slowing down the rate at which the cell dies.

The team tested the intervention in yeast cells and found that those under the control of the gene oscillators lived about 82 percent longer than normally aged yeast cells. The scientists say this is the most dramatic lifespan extension of any previous genetic or chemical anti-aging intervention, which typically works by trying to return cells to a more youthful state.

Of course, humans are not yeast cells, so there is still a long way to go before we routinely celebrate our 50th anniversary. But the team is now investigating applying the technique to human cells, including stem cells and neurons.

The study was published in the journal science.

source: University of California, San Diego