Scientists tweaked yeast cells to age in slow-motion, here is the proof

Like how electric circuits control our home appliances, gene regulatory circuits control various physiological functions, including aging. In their previous studies, the UCSD researchers discovered that although all cells age and die, they don’t follow the same pathway. Even cells with similar genetic composition could take on different aging routes.

They later found two different ways in which cells age and die. For instance, aging in about 50 percent of cells occurs as a result of the weakening of their mitochondria due to which they suffer energy losses and eventually die. 

The rest of the cells age as their DNA becomes less and less stable over time, the cell stops growing, starts deteriorating, and finally succumbs to death.  

The “smart aging process”

The interactions between genes in a circuit are defined by a part of their DNA sequences called promoters. During the current study, the researchers realized that just by changing these sequences, they could exercise control over the genetic interactions taking place in a circuit. 

Using the same concept, they rewired the gene regulatory circuit in the cells of Saccharomyces cerevisiae (commonly known as baker’s yeast) to function like a gene oscillator that caused the cells to continue oscillating while aging.

So basically, instead of following one of the two aging pathways and aging naturally, the yeast cells were now periodically switching between both pathways and not completing the aging process through either. 

This negative loop significantly halted the cellular aging process and prevented the yeast cells from deteriorating naturally.  

“In natural aging, the cell has to age through one of the two pre-destined paths, accumulating different types of damage. On each path, damage accumulation will be accelerated toward the late stage of aging. On the “smart aging process, the cell can keep cycling between two aging paths so that it will slow damage accumulation and extend lifespan.” senior study author and a professor at UCSD, Nan Hao told IE. 

When the researchers compared the lifespan of rewired yeast cells with another group of yeast cells that were allowed to age normally, they noticed that the former demonstrated 82 percent more longevity than the latter. 

Can gene oscillators increase the average human lifespan?

When gene regulatory circuits turn into gene oscillators, cells enter into a loop between two aging paths because the genes in a gene oscillator produce two master aging regulators or aging proteins. 

Interestingly, both of these proteins regulate each other’s level and their levels keep oscillating during aging. These levels also determine which aging path the cell will be on, so the cell can keep cycling between two paths. 

When asked if similar approaches in the future might also allow humans to reverse or stop the aging process up to a large extent, Hao said, “I can’t see why we cannot achieve that. A lot of scientists are working on that. The major concerns are mostly on ethics and safety. Another aspect is that our strategy is to slow aging, which is arguably more realistic than most other attempts to completely reverse aging.” 

Hao and his team also used computers to simulate the natural aging process and test different methods to come up with the best slow aging strategy. He told IE, “This is the first time this computationally-guided engineering-based approach to be used in aging research.”

Hao further added, “The most important takeaway is that our work is a proof-of-concept, showing that, like mechanical engineers can fix and enhance our cars so that they can last longer, we can also use the same engineering approach to modify and enhance our cells to live longer.”

The proposed circuit rewiring approach might become a universal strategy to slow cell deterioration and aging in the future. However, the study is conducted only on yeast, which is a simple eukaryote. The researchers need to test this strategy in more complex organisms.

“Whether it is safe in humans is an open question that needs to be tested. Our immediate next step is to apply the same approach to various types of human cells, which are related to the aging of the whole organisms,” said Hao.  

The study is published in the journal Science.