07 June 2023

Bioengineers slowed the aging of living cells with a gene oscillator

Researchers used genetic modification to slow the "wear and tear" and aging of living cells. The study was published in the journal Science.

Bioengineers at the University of California, San Diego, have modified the genetic circuitry that controls cell aging. They developed a negative feedback loop to slow the aging process and extend cellular lifespan.

In previous studies, scientists found that cells follow a cascade of molecular changes throughout their lives until they eventually degenerate and die. Yet genetically identical cells in the same environment can follow different aging pathways. About half of the cells age due to gradual decrease of DNA stability, the other half due to degradation of mitochondria, the "cellular powerhouses".

The traditional aging "circuit" works like a toggle switch that triggers one of the two processes, the scientists explain. They used genetic editing to create a negative feedback loop. The rearranged circuitry works like clockwork, an oscillator that makes periodic switches. It forces the cell to periodically switch between two deleterious "old" states, avoiding prolonged stay in one of them and thereby slowing cell degeneration.

The researchers tested their method on Saccharomyces cerevisiae yeast cells. The analysis showed that the genetic modification under the control of the "oscillator" increased the life span of the cells by 82%.

"Our oscillatory cells live longer than any of the longest-lived strains previously identified by objective genetic screening," Nan Hao, co-author of the study.
The findings could lay the groundwork for developing synthetic gene circuits to effectively extend the lifespan of more complex organisms, the scientists believe. They are working to investigate the aging mechanisms of various human cells, including stem and nerve cells.

Source: Engineering longevity—design of a synthetic gene oscillator to slow cellular aging | Science

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