Longevity: Scientists use genetic rewiring to increase cell lifespan

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Have scientists found new clues to improve longevity? d3sign/Getty Images
  • Human lifespan has increased during the 20th and 21st centuries, but these increases are slowing, so scientists continue to search for ways to improve longevity.
  • Healthy eating, hygiene, and medical care have all contributed to increased lifespans, and now researchers are turning their attention to genetics.
  • In a new proof-of-concept study, researchers nearly doubled the lifespan of yeast cells by genetically rewiring the circuitry that controls aging.
  • Their findings could pave the way to increasing the longevity of more complex organisms and, possibly, even humans.

We all strive for a long and healthy life, but can you extend your life? The National Institutes of Health (NIH) tell us that the best way to increase lifespan is to eat well, get quality sleep, exercise regularly, get regular checkups, and avoid bad habits such as smoking and drinking too much alcohol.

Scientists fighting the aging process have extended the lifespans of worms, mice, and even monkeys. But could they do the same for people?

Today, a team from the University of California, San Diego has managed to extend the lifespan of a simple organism by around 80% by manipulating the genetic circuitry that controls aging.

The proof-of-concept study performed in yeast is published in Science.

The UC San Diego research team has been studying cellular aging for several years, finding that cells follow a cascade of molecular changes throughout their lives until they eventually degenerate and die. However, they discovered that not all cells age equally, and that was the focus of their new research.

They first used computer simulations of cellular aging to test their ideas before moving on to modifying the aging circuits of the single-celled yeast Saccharomyces cerevisiae.

They found that cells follow one of two aging pathways. About half of the cells suffered a progressive decline in the stability of their DNA (nucleolar aging); for the rest, the aging trajectory was characterized by a decrease in their mitochondria – the organelles that provide energy to the cell (mitochondrial aging).

To control cell aging, they manipulated the expression of two transcriptional regulators — molecules that determine which genes are active in the cell. Silent information regulator 2 (Sir2) drives nucleolar decline (leading to DNA instability), and heme activator protein 4 (Hap4) is associated with mitochondrial activity.

When one of these regulators is expressed and therefore active, it prevents the other from expressing itself. The researchers therefore designed a synthetic gene oscillator to rewire this mechanism. By generating sustained oscillations between the two types of cellular degeneration in individual cells, they prevented cells from following either of the two aging pathways. The lifespan of these cells has increased.

Professor Nan Hao, lead author of the study and co-director of UC San Diego’s Institute for Synthetic Biology, said Medical News Today:

“Our work is a proof of concept, showing that just as mechanical engineers can fix and improve our cars so they can last longer, we can also use the same engineering approach to modify and improve our airframes so that “they live longer. The highlight is our approach to achieving this: using computers to simulate the natural aging system and guide rational system design and engineering to extend life.”

By creating the gene oscillator, the scientists continually switched yeast cells between the two aging pathways, preventing them from going down their predestined path of decline and death, slowing cell degeneration.

Those yeast cells that were synthetically rewired and aged under the guidance of the synthetic oscillator had an 82% increase in lifespan compared to control cells.

And the genetic manipulation didn’t seem to affect them negatively, according to Professor Hao, who said DTM: “Yeast cells survive well with a rapid growth rate.”

“This is the first time that this computationally-guided engineering approach [has been] used in aging research. I don’t see why we can’t apply the same strategy to human cells.

– Professor Nan Hao

All cells contain gene regulatory circuits which are responsible for many physiological functions, including aging, so in theory a similar approach could work in human cells.

The goal may be not only to prolong the life of more complex organisms, but also to prolong the life of certain cells within organisms to prevent degenerative diseases.

However, Professor Hao cautioned that they don’t know if increasing longevity might affect cells in other ways:

“It’s a deep biological question. Our current hypothesis is that cell longevity is not an evolutionarily selected trait. Cells must first be able to survive in a stressful, unpredictable and rapidly changing environment.

“It is possible that our long-lived cells are less resistant to certain types of stress in the environment. So basically extending longevity might sacrifice some normal functions, but that’s just a guess,” he added..

Professor Hao suggested there might be potential for this approach in people:

“Both regulators have counterparts in humans, so I think the same strategy could be applied to human cells. In fact, this is our next step in the future.

And Professor Howard Salis, principal investigator at Salis Lab, Penn State University, who was not involved in the study, agreed:

“If the collective goal of these interventions is to maintain healthier cellular states, then the risk and morbidity of age-associated diseases will be reduced.”

However, it is still in its infancy, and although this study shows that it is possible to turn off aging mechanisms in a single-celled organism, many questions still need to be answered before the technology can be applied. to the man.

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