Longevity: Scientists are using genetic rewiring to extend the lifespan of cells

A hand place on a very old log with dark rings

A hand place on a very old log with dark ringsShare on Pinterest
Have scientists found new clues to improve longevity? d3sign/GettyImages
  • Human lifespans increased in the 20th and 21st centuries, but this increase is slowing, so scientists continue to look for ways to improve longevity.
  • Healthy diet, hygiene, and medical care have all contributed to lengthening lifespans, and now researchers are turning to genetics.
  • In a new proof-of-concept study, researchers have nearly doubled the lifespan of yeast cells by genetically rewiring the circuitry that controls aging.
  • Their findings could pave the way to longer lifespans in more complex organisms and possibly even humans.

We all strive to live long and healthy lives, but can you extend your life? The National Institutes of Health (NIH) tells us that the best way to extend lifespan is to eat well, sleep well, exercise regularly, get regular medical check-ups, and avoid bad habits like smoking and avoid excessive alcohol consumption.

Scientists working to fight the aging process have increased the lifespan of worms, mice and even monkeys. But could they do the same for humans?

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

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

The UC San Diego research team has been studying cellular aging for several years and discovers that cells follow a cascade of molecular changes throughout their lives before eventually degenerating and dying. However, they found that not all cells age in the same way, and this was the focus of their new research.

They first used computer simulations of cell aging to test their ideas before setting out to modify aging circuits in the unicellular yeast Saccharomyces cerevisiae.

They discovered that the cells follow one of two aging pathways. About half of the cells gradually lost their DNA stability (nucleolar aging); moreover, the aging path was characterized by a decrease in their values mitochondria – the organelles that provide energy to the cell (mitochondrial aging).

To control cell senescence, they manipulated the expression of two conserved ones transcription regulators — Molecules that determine which genes are active in the cell. Silent information regulator 2 (Sir2) drives nucleolar decline (resulting in DNA instability), and heme activator protein 4 (Hap4) is linked to mitochondrial activity.

When one of these regulators is expressed and therefore active, it prevents the other from being expressed. Therefore, the researchers developed a synthetic gene oscillator to rewire this mechanism. By creating sustained oscillations between the two types of cellular degeneration in individual cells, they prevented the cells from following either aging pathway. The lifespan of these cells is extended.

Prof. Nan Hao, senior author of the study and co-director of UC San Diego’s Institute of Synthetic Biology, said Medical news today:

“Our work is a proof of concept and shows that just like machine builders can fix and improve our cars to make them last longer, we can also use the same engineering approach to modify and improve our cells to make them last longer life. The highlight is our approach to achieve this: using computers to simulate the natural aging system and guiding the design and rational construction of the system to extend the service life.”

By creating the gene oscillator, the scientists allowed the yeast cells to continuously switch between the two aging pathways, preventing them from embarking on their predetermined path of decline and death, thereby slowing down the cells’ degeneration.

These yeast cells, synthetically rewired and aged under the direction of the synthetic oscillator, had an 82% longer lifespan compared to control cells.

And the genetic manipulation didn’t seem to affect them adversely, according to Prof Hao, who narrated MNT: “The yeast cells survive well with a rapid growth rate.”

“This is the first time this computer-aided engineering-based approach has been used [has been] used in aging research. I don’t understand why we can’t apply the same strategy to human cells.”

– Prof. Nan Hao

All cells included gene regulatory circuits responsible for many physiological functions, including aging, so theoretically a similar approach could work in human cells.

The goal can be not only to increase the lifespan of more complex organisms, but also to increase the lifespan of some cells within organisms to prevent degenerative diseases.

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

“It’s a deep biological question. Our current hypothesis is that cell longevity is not a trait chosen by evolution. Cells must first be able to survive in the rapidly changing, unpredictable stress environment.”

“There is a possibility that our engineered long-lived cells may be less resilient to certain types of environmental stresses. Basically, increasing lifespan might sacrifice some normal functions, but that’s just a hypothesis,” he added.

Prof. Hao suggested that this approach might have potential in humans:

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

And Prof. Howard Salis, Principal Investigator at Salis Lab, Penn State University, who was not involved in the study, agreed:

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

It’s still early days, however, and while this study shows that it’s possible to turn off aging mechanisms in a unicellular organism, many questions need to be answered before the technology can be applied to humans.

#Longevity #Scientists #genetic #rewiring #extend #lifespan #cells

Jamal Murray (27) of the Denver Nuggets smiles after drawing a hard foul from Chris Paul (3) of the...

Suns were bowled over by Nuggets, Jamal Murray and Math in the Game 1 loss

Clumps or knots of worms

Researchers uncover the bizarre math behind ‘ultra-fast’ worm blobs