Scientists increased longevity in yeast with a biosynthetic ‘clock’, increasing the promise of an anti-ageing pill.
Researchers were able to rewire the circuit that controls normal deterioration in the single celled organism, offering hope of preventing human illnesses.
‘Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally-designed gene circuits that slow ageing,’ said Senior author Professor Nan Hao, of the University of California, San Diego.
Humans have gene regulatory circuits responsible for ageing – just like the humble fungi.
The US team used microfluidics and time-lapse microscopy to track the ageing processes across yeast’s lifespan.
Cells exposed to the oscillator device survived almost twice as long as normal controls.
‘Our oscillator cells live longer than any of the longest-lived strains previously identified by unbiased genetic screens,’ said Prof Hao.
‘Our work represents a proof-of-concept example, demonstrating the successful application of synthetic biology to reprogram the cellular ageing process,’
Professor Hao believes that the study may lay the foundation for designing synthetic gene circuits to effectively promote longevity in more complex organisms.
Yeast and humans share similar genes, despite diverging from a common ancestor around a billion years ago.
‘These gene circuits can operate like our home electric circuits that control devices like appliances and automobiles,’ said Prof Hao.
From its normal role functioning like a toggle switch, the reseasrchers engineered a negative feedback loop to stall ageing.
It operates as a clock-like device, called a gene oscillator, that drives the cell to periodically switch between two detrimental ‘aged’ states, avoiding prolonged commitment to either, and thereby slowing degeneration.
Computer simulations helped them design and build the circuit in the cell.
‘This is the first time computationally guided synthetic biology and engineering principles were used to rationally redesign gene circuits and reprogram the ageing process to effectively promote longevity,’ said Prof Hao.
They previously discovered cells take one of two paths. One leads to healthy ageing, while cells that go the other route decline much more quickly as their machinery stutters and churns out broken proteins.
And the scientists found the molecular ‘switchboard’ that determines which fate cells will have.
With this newly found information, the team made a computer model for cellular aging and found DNA tweaks that could make yeast cells live about twice as long, thus extending the organism’s lifespan.
Distinct from numerous chemical and genetic attempts to force cells into artificial states of ‘youth’, the new research suggests slowing the ticks of the ageing clock is possible by actively preventing cells from committing to a pre-destined path of decline and death.
The clock-like gene oscillators described in the journal Science could be a universal system to achieve that.
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