Rewired genetic ‘clock’ slows aging and increases cellular lifespan

Scientists have developed an oscillating genetic ‘clock’ that significantly slows down the aging process in tests in yeast cells.  Depositphotos

The familiar symptoms of aging that we all dread begin on the cellular level. Every one of our trillions of cells undergoes a cascade of molecular changes over its lifetime, sustaining different types of damage until eventually they can no longer function effectively and die off. This contributes to age-related health decline, from wrinkles and gray hair to increased risks of many diseases.

In a previous study, the UC San Diego team found that cells seem to age through one of two specific processes, committing to one path and not straying to the other. The split is roughly 50/50, even among cells from the same genetic lineage in the same environment. One path involves the decline of DNA stability, and the other the decline of mitochondria, which produce energy for the cells. Either way, the end result is the same – cellular death.

For the new study, the team developed a way to slow down cellular aging by allowing cells to swing between these two different processes. To continue the pathway analogy, you’d reach your final destination (cell death) faster if you follow one path straight to the end, but by running back and forth between the two it’ll take much longer.

To pull this off, the team rewired a central gene regulatory circuit that controls cell aging. Usually it works like a toggle switch, sending a particular cell down a particular path, but in this case the researchers tweaked it to function as a gene oscillator. That triggers a cell to periodically switch from one path to another, slowing down the arrival at the destination of cell death.

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

Of course, humans aren’t yeast cells, so there’s still a long way to go before we’re routinely celebrating our sesquicentennials. But the team is now looking into applying the technique to human cells, including stem cells and neurons.

The research was published in the journal Science.

Source: UC San Diego

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