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Boosting a single gene involved in processing RNA can make ageing human cells look younger and help old mice live longer, healthier lives, according to a new study. The gene, SRSF1, controls splicing, the way genetic messages are edited before they are used to make proteins, and its activity falls as cells age.
The team first built a machine-learning "clock" that estimates the age of human skin cells from their gene activity, trained on cells from donors aged between 1 and 96. They used it to screen dozens of genes linked to ageing, switching each one on in older cells. SRSF1 had the strongest rejuvenating effect, comparable to the Yamanaka factors used in cellular reprogramming.
In cells, extra SRSF1 reduced markers of senescence, inflammation and protein stress, and switched on DNA repair. Unlike reprogramming with Yamanaka factors, which can strip cells of their identity and raise the risk of tumours, SRSF1 made cells younger at the molecular level while they kept their normal identity and shape.
The researchers then used a virus to deliver SRSF1, mainly to the liver, in aged female mice. A short burst of extra SRSF1 cut frailty by 44%, sped up wound healing, improved physical function and extended median lifespan by 14%. Gene activity in the liver showed fewer signs of age-related stress and inflammation.
The mouse study was small, with nine or ten animals per group. Keeping SRSF1 switched on continuously produced higher levels without obvious toxicity, but did not improve wound repair or muscle regeneration, suggesting that timing and dose matter. How changes in splicing lead to rejuvenation is still unclear, and the approach has not been tested in people.
The research was led by George Church at Harvard Medical School and published in Nature Aging.
