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Scientists use genetic rewiring to increase cells’ lifespan

Scientists use genetic rewiring to increase cells’ lifespan

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Throughout the 20th and 21st centuries, human lifespans have increased, but those increases are slowing down, so researchers are still looking for ways to extend life.

Researchers are now focusing on genetics after examining how healthy meals, hygiene, and medical treatment have all contributed to the gains in lifespan.

By genetically rewiring the circuit that regulates aging, researchers in a recent proof-of-concept study nearly doubled the lifespan of yeast cells. Their research could lead to increased longevity in more advanced organisms, including perhaps even humans.

Can you extend your life? Everyone wants to live long, healthy lives. The National Institutes of Health (NIH) advise us that the best method to lengthen lifespan is to eat a healthy diet, get enough sleep, exercise frequently, have routine checkups with a doctor, and abstain from unhealthy habits like smoking and binge drinking alcohol.

Worms, mice, and even monkeys have lived longer thanks to research being done by scientists to slow down the aging process. Could they, however, do the same for people?

Now, by altering the genetic circuit that regulates aging, a team from the University of California, San Diego, has succeeded in extending the lifespan of a simple organism by about 80%.

The role of synthetic biology in cell ageing

The UC San Diego research team has been investigating the aging process of cells for several years and has found that cells undergo a series of chemical changes as they age, leading to their eventual degeneration and death. But they discovered that not all cells deteriorate in the same way, and this was the subject of their most recent study.

Before making changes to the aging circuits in the single-celled yeast Saccharomyces cerevisiae, they first tested their theories using computer models of cell aging.

They found that there were two ageing processes that the cells went through. For almost half of the cells, ageing was characterised by a loss in the stability of their DNA (nucleolar ageing); for the remaining cells, ageing was characterised by a decline in their mitochondria, the organelles that produce the cell’s energy (mitochondrial ageing).

Increasing lifespan via manipulating gene expression

The expression of two conserved transcriptional regulator molecules, which govern which genes are active in the cell, was altered to control the aging of the cells. Heme activator protein 4 (Hap4) is connected to mitochondrial function, while silent information regulator 2 (Sir2) promotes nucleolar decrease (resulting in DNA instability).

The researchers created a synthetic gene oscillator to rewire this system such that when one of these regulators is expressed and consequently active, it prevents the other from being expressed. They stopped the cells from progressing along either of the two ageing pathways by creating long-lasting oscillations between the two types of cellular degeneration in individual cells. These cells lived longer than usual.

Professor Nan Hao, the study’s principal author, and co-director of the Synthetic Biology Institute at UC San Diego, stated, “Our research serves as a proof-of-concept, demonstrating that, just as mechanical engineers can repair and improve our cars so they last longer, we can also apply the same engineering method to modify and improve our cells so they live longer. The key to this is how we went about doing it: by simulating the natural aging process on computers to inform the engineering of the system and increase longevity.“

Life expectancy nearly quadrupled following genetic rewiring

The scientists forced the yeast cells to alternate between the two ageing pathways on a constant basis by engineering the gene oscillator. By doing this, they prevented the yeast cells from choosing their predetermined course of decline and death and slowed the cells’ ageing process.

The longevity of yeast cells that were artificially rewired and aged under the supervision of the artificial oscillator increased by 82% in comparison to control cells.

And genetic engineering did not appear to hurt them, according to Prof. Hao, told: “The yeast cells survive nicely with a fast growth rate.”

Application that might lengthen life

Theoretically, a similar strategy may be effective in human cells because all cells include gene regulatory circuits that are in charge of numerous physiological processes, including aging.

The goal might not just be to increase the lifespan of more complex species but also to increase the lifespan of particular cells inside those organisms to stave off degenerative diseases.

Prof. Hao issued a warning, noting that it is unknown whether lengthening life might have further effects on cells.

“That is a complex biological query. The length of the cell is not a property that has been selected through evolution, according to our current theory. First, cells must be capable of surviving in an unpredictable, harsh environment that is always changing.

“There is a chance that our long-lived modified cells won’t be as resilient to particular environmental pressures. In other words, extending longevity may lose some common functions, but it is only a theory,” he continued.

Implications for prolonging human healthy life years

There might be a promise for this strategy in people, according to Prof. Hao, “Since both of the two regulators have human equivalents, I think that human cells could benefit from the same approach. In actuality, it will be our next move.”

Aside from the study, Prof. Howard Salis, Principal Investigator at the Salis Lab at Penn State University, concurred:

The risk and morbidity of age-related diseases will decrease if the overall goal of these interventions is to preserve better cell states, according to the study.

Though this study demonstrates that it is possible to turn off the ageing process in a single-celled organism, it is still very early in the development of the technology, and many questions need to be resolved before it can be used on humans.

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