Researchers find a way to slow yeast cell aging by 82%

By Lisa Marie Basile | Fact-checked by Davi Sherman
Published May 4, 2023

Key Takeaways

  • A group of researchers at the University of California San Diego found that yeast cells follow two pathways to aging and eventual death. 

  • The researchers manipulated the “naturally occurring toggle switch,” which determines how cells die. By rewiring this toggle, the researchers were able to increase the life span of yeast cells by 82%, relative to control cells.

  • The researchers believe this engineering-based approach may be applied to human stem cells in the future.

New research from the University of California San Diego (UCSD) shows that it is possible to manipulate the circuits that control how cells age.[] The research group’s newest findings—published in Science on April 28—found that they could increase the life span of yeast cells by 82%. 

New findings follow prior research

These findings follow earlier research, published by the UCSD research group in 2020, on the mechanisms of a yeast cell’s aging process.[] This earlier research found that yeast cells take two distinct pathways when aging: Half of the cells age and die through chromatin instability (chromatin is made up of DNA, RNA, and protein) and half age and die due to mitochondrial decline (mitochondria generate most of the chemical energy needed to fulfill cells’ biochemical reactions).[] 

Yeast cells are model organisms

The group’s research utilized yeast cells—specifically Saccharomyces cerevisiae cellswhich were said to provide a “genetically tractable model for the aging of mitotic cell types such as stem cells.” In fact, a 2022 review in Cells states that, “A considerable portion of our knowledge on the genes and pathways involved in cellular growth, resistance to toxic agents, and death has in fact been generated using this model organism [S. cerevisiae].”[]

To observe the aging process of these cells, the researchers employed microfluidics (technology that can process or manipulate small amounts of fluidics[]) and time-lapse microscopy (a tool for real-time imaging of living cells).[] 

To build on this research, the UCSD group explained how they subsequently manipulated the “naturally occurring toggle switch [that] underlies fate decisions toward either nucleolar or mitochondrial decline during the aging of yeast cells.”

"We rewired this endogenous toggle to engineer an autonomous genetic clock that generates sustained oscillations between the nucleolar and mitochondrial aging processes in individual cells. "

UCSD researchers, "Science"

This “toggle switch,” the authors wrote, is made up of the lysine deacetylase Sir2 and heme-activated protein (HAP) complex, which are “deeply conserved, well-characterized transcriptional regulators that control yeast aging and life span.” By understanding how the Sir2 and HAP pathways modulate the aging of the cells, the researchers “rewired their interactions into a negative feedback loop and created a gene oscillator that functions to maintain cellular homeostasis.”

Potential design to slow aging

In essence, the team’s engineered gene oscillator ensures the cells don’t remain in any one state long enough to age. “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 wrote in the 2023 report.

This engineered process increased the life span of yeast cells by 82% compared with that of control cells.

“This type of engineering-based approach is called ‘synthetic biology,’” Nan Hao, associate director of UCSD’s Synthetic Biology Institute and senior author of the study, tells MDLinx. “We engineered a gene oscillator in the cell under guidance of computer simulations, and it can indeed extend the cell’s lifespan very effectively.” 

With a computer simulation of a cell’s typical aging circuit, the team could first run tests on the simulation before actually modifying the cells themselves. “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,” Hao told Newswise.[] 

Engineering and reprograming cellular functions

Hao also told MDLinx that the group’s findings were incredibly revealing: “The most interesting thing, for me, is the fact that we can use [an] engineering-based approach to rationally reprogram cell functions—even the complex process of cell aging. It worked so nicely.”

What are the implications of these findings? This research presents a sort of proof-of-concept, Hao says.

"The same strategy may be applicable for more complex organisms, including humans. We plan to test that in human cells, such as stem cells."

Nan Hao, associate director, UCSD’s Synthetic Biology Institute

The future of medicine could also be impacted by this research, Hao adds. “Synthetic biology for engineering cells could be a powerful approach for advancing cell-based therapies against age-related diseases. This really opens the door to modify and enhance our cells, the same way electrical engineers fix our devices.” 

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