Wednesday, May 24, 2023

Rewired genetic 'clock' slows aging and increases cellular lifespan in yeast by 80%

Good news! Better than plastic surgery and Botox injections? 😊 This sounds very promising to halt or delay aging!

Journal Science found this paper so interesting that they provided a perspective and an editor's summary for it.

"Yeast cells have a transcriptional toggle switch that leads them to die by one of two fates: One causes death by nucleolar decline, the other by mitochondrial decay. By rewiring this transcriptional switch into a negative-feedback loop, Zhou et al. were able to cause yeast cells to oscillate between the two states and increase their life span by 82% ... These results represent a step forward toward the use of engineering principles to design synthetic gene circuits that control complex biological traits."

"... These advances resulted in a dramatically extended cellular lifespan, setting a new record for life extension through genetic and chemical interventions. ...
the researchers in this study first used computer simulations of how the core aging circuit operates. ...
Several years ago the multidisciplinary UC San Diego research team began studying the mechanisms behind cell aging, a complex biological process that underlies human longevity and many diseases. They discovered that cells follow a cascade of molecular changes through their entire lifespan until they eventually degenerate and die. But they noticed that cells of the same genetic material and within the same environment can travel along distinct aging routes. About half of the cells age through a gradual decline in the stability of DNA, where genetic information is stored. The other half ages along a path tied to the decline of mitochondria, the energy production units of cells. ..."

From the abstract of the perspective:
"Over the past decade, cellular aging research has been accelerated by the identification of pathways that control the onset of age-associated cell states (the so-called hallmarks of aging) alongside the development of candidate therapeutics that attempt to delay or reverse the onset of aging (1). But what if cells were preprogrammed to undergo cellular aging? Cellular aging in yeast (Saccharomyces cerevisiae) was shown to be controlled by a genetic circuit that forces cells to either slow down heme biosynthesis, leading to mitochondrial dysfunction, or lose their ability to engage in chromatin silencing, leading to ribosomal DNA (rDNA) instability and fragmented nucleoli (2). Simple interventions to this evolutionarily conserved genetic circuit (e.g., overexpressing the key regulators) increased the cell’s longevity by modest amounts. On page 376 of this issue, Zhou et al. (3) reveal that introducing designed genetic circuitry to rewire these dynamics increased cellular longevity by 80%."

From the abstract:
"Synthetic biology enables the design of gene networks to confer specific biological functions, yet it remains a challenge to rationally engineer a biological trait as complex as longevity. A naturally occurring toggle switch underlies fate decisions toward either nucleolar or mitochondrial decline during the aging of yeast cells. We rewired this endogenous toggle to engineer an autonomous genetic clock that generates sustained oscillations between the nucleolar and mitochondrial aging processes in individual cells. These oscillations increased cellular life span through the delay of the commitment to aging that resulted from either the loss of chromatin silencing or the depletion of heme. Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally designed gene circuits that slow aging."

Rewired genetic 'clock' slows aging and increases cellular lifespan

Scientists Slow Aging by Engineering Longevity in Cells Studying yeast cells, researchers build a biosynthetic genetic ‘clock’ to extend lifespan
Published Date

Genetic circuitry boosts cell longevity (no public access) Reprogramming cellular dynamics is used to study and delay the onset of aging in yeast 

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