Bioengineered cells could expand lifespan, study finds

(CN) — Humans now live on average much longer than they ever have in the past, a feat that can be attributed to medical advances and overall higher quality of life, although aging is still an inevitability. But now scientists think it may be possible to slow aging and further extend lifespans through genetic bioengineering.

A University of California San Diego research team details in a study published Thursday in Science their investigation of the mechanism of cellular aging and how they figured out how to rewire cells to extend their lifespan to slow aging and increase life expectancy.

Lifespans, human or otherwise, are dictated by the rate at which the cells of the organism age and deteriorate. Eventually, the cells can no longer continue dividing and multiplying to sustain themselves and they die. Researchers have long investigated these basic life building blocks to find a way to improve their function.

In contrast to other cell aging research, the team’s work doesn’t try to reset the cell to a younger phase to extend life, but rather builds on research also published by a University of California San Diego research team in 2020, which first discovered that cells could follow two separate paths as they age — one involving the ribosome-producing nucleolus, another through a mitochondrial path.

The study showed that the cells will only opt to go through one of these processes in a typical lifetime, with half of cells in similar genetic environments aging through the decline of DNA stability and half through reduced energy production. But researchers found that it could be possible to genetically reprogram the cell to create an alternate aging route that could extend lifespans.

Now, researchers describe a “gene oscillator” that can cycle between the two routes by rewiring the regulatory circuit in the gene that controls aging. The oscillator device operates by periodically switching between the nucleolus and the mitochondrial routes. The hop back and forth between the two prevents the cell from entirely committing to one route for too long, which prevents the cell from degenerating as quickly.

“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," the study’s senior author, Professor Nan Hao of the university’s School of Biological Sciences’ Department of Molecular Biology, said in a statement.

Using Saccharomyces cerevisiae yeast cells as a model and computer simulations as a guide, the research team rewired the cells’ aging process to prevent them from progressing through their predetermined paths, shifting between the two with their synthetic gene oscillator device. The team tracked the progress of the cells’ aging by developing and using microfluidics and time-lapse microscopy.

“Our oscillator cells live longer than any of the longest-lived strains previously identified by unbiased genetic screens,” said Hao.

According to the study, those yeast cells demonstrated an 82% increase in lifespan compared to typical aging cells.

Hao and the team’s research establishes a basis for cellular bioengineering that could support research into expanding the lifespan of more complex organisms. Researchers also hope to expand their research to other human cell types, including stem cells and neurons.

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