An overworked protein that causes yeast to age when it neglects one of its functions may trigger ageing in mice too. If the same effect is found in people, it may suggest new ways to halt or reverse age-related disease.
As we get older, genes can start to be expressed in the wrong body tissues – a process that is thought to contribute to diseases like diabetes and Alzheimer’s. But while sunlight or chemicals are known to cause limited DNA damage, how more widespread changes in gene expression come about has been unclear.
To investigate, David Sinclair and colleagues at Harvard Medical School turned to yeast cells. These produce a dual-function protein called Sir2 that, while being involved in DNA repair, also helps keep certain genes switched off.
As yeast cells age, the protein can’t do both jobs and neglects its role as a gene suppressor.
Now Sinclair’s team has shown that SIRT1, the mammalian version of Sir2, also begins to neglect its gene-suppressor role in mice whose DNA is damaged, and that this may contribute to ageing.
This raises the hope that, if gene-suppressing proteins become similarly overworked in ageing people, they could become prime targets for drugs to keep us young.
This possibility is boosted by the team’s finding that mice engineered to over-express the gene for SIRT1 were better at repairing DNA, more resistant to cancer, and maintained a more youthful pattern of gene expression.
“The most exciting thing is that this work may unify in a single molecular pathway what we know about ageing in different organisms such as yeast and mammals,” says Maria Blasco of the Spanish National Cancer Research Centre in Madrid, who works on mechanisms of cellular ageing.
“It opens up the possibility of restoring youth in the elderly by re-establishing a useful pattern of gene expression,” adds Sinclair.