Good news! Towards the fountain of youth!
"Ageing seems to affect cellular processes in the same way across five very different kinds of life — humans, fruit flies, rats, mice and worms ...
Many studies have explored ageing’s effects on gene expression, but few have investigated how it affects transcription — the process whereby genetic information is copied from a blueprint DNA strand to RNA molecules ...
The researchers measured how ageing changed the speed at which the enzyme that drives transcription, RNA polymerase II (Pol II), moved along the DNA strand as it made the RNA copy. They found that, on average, Pol II became faster with age, but less precise and more error-prone across all five groups. ...
team tracked the survival of fruit flies and worms that carried a mutation that slowed Pol II down. These animals lived 10% to 20% longer than their non-mutant counterparts. ...
the researchers found that ageing cells contained fewer nucleosomes, smoothing the path for Pol II to travel faster. When the team boosted the expression of histones in the cells, Pol II moved at a slower pace. In fruit flies, the elevated histone levels seemed to increase their lifespans. ..."
Many studies have explored ageing’s effects on gene expression, but few have investigated how it affects transcription — the process whereby genetic information is copied from a blueprint DNA strand to RNA molecules ...
The researchers measured how ageing changed the speed at which the enzyme that drives transcription, RNA polymerase II (Pol II), moved along the DNA strand as it made the RNA copy. They found that, on average, Pol II became faster with age, but less precise and more error-prone across all five groups. ...
team tracked the survival of fruit flies and worms that carried a mutation that slowed Pol II down. These animals lived 10% to 20% longer than their non-mutant counterparts. ...
the researchers found that ageing cells contained fewer nucleosomes, smoothing the path for Pol II to travel faster. When the team boosted the expression of histones in the cells, Pol II moved at a slower pace. In fruit flies, the elevated histone levels seemed to increase their lifespans. ..."
From the abstract:
"Physiological homeostasis becomes compromised during ageing, as a result of impairment of cellular processes, including transcription and RNA splicing. However, the molecular mechanisms leading to the loss of transcriptional fidelity are so far elusive, as are ways of preventing it. Here we profiled and analysed genome-wide, ageing-related changes in transcriptional processes across different organisms: nematodes, fruitflies, mice, rats and humans. The average transcriptional elongation speed (RNA polymerase II speed) increased with age in all five species. Along with these changes in elongation speed, we observed changes in splicing, including a reduction of unspliced transcripts and the formation of more circular RNAs. Two lifespan-extending interventions, dietary restriction and lowered insulin–IGF signalling, both reversed most of these ageing-related changes. Genetic variants in RNA polymerase II that reduced its speed in worms and flies increased their lifespan. Similarly, reducing the speed of RNA polymerase II by overexpressing histone components, to counter age-associated changes in nucleosome positioning, also extended lifespan in flies and the division potential of human cells. Our findings uncover fundamental molecular mechanisms underlying animal ageing and lifespan-extending interventions, and point to possible preventive measures."
Ageing-associated changes in transcriptional elongation influence longevity (open access)
RNA polymerase (blue) unwinds DNA (violet), using it as a template to produce a strand of messenger RNA (red). In aged cells, this process accelerates.
Fig. 5: Histone overexpression slows down entry into senescence and decreases Pol II speed.
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