Protein factor slows cellular ageing and extends lifespan in mice
Researchers have identified a protein that makes aged cells look biologically younger and extends the lifespan of mice. Notably, it works differently from the riskier reprogramming approaches that have attracted much recent attention.
Much current research focuses on rejuvenating cells using Yamanaka factors: proteins that can reset cells toward an embryonic state. But this carries risks, including loss of cell identity and increased likelihood of tumour formation. Researchers have therefore been seeking safer alternatives.
Machine learning as a filter
A team trained a computational model on gene activity profiles from human skin cells drawn from donors across a wide age range. This allowed the model to estimate the biological age of cells based on their gene expression patterns. The researchers then screened a panel of genes to find candidates that could shift old cells toward a more youthful gene activity profile.
The top candidate was SRSF1, a protein involved in RNA splicing, the process by which cells select which parts of a gene’s instructions are used to make proteins. The study showed that increasing SRSF1 activity reduced markers of cellular senescence (cells that stop dividing but do not die), proteostatic stress (disruption of the cell’s protein balance), and low-grade chronic inflammation. Crucially, the rejuvenated cells kept their identity as skin cells and did not switch on embryonic stem cell programmes.
Effect in mice
When SRSF1 was delivered to aged mice, the protein accumulated primarily in the liver. The mice showed a measurably slower rate of ageing and lived longer. The researchers emphasise that the mechanisms are not yet fully understood and that mouse results do not automatically translate to humans. Further studies are needed to determine whether SRSF1-based approaches are safe and effective in people.
Search terms to explore further: RNA splicing factors cellular ageing transcriptome, cellular senescence inflammaging inhibition, biological age gene expression skin cells