Aging may be a case of neglect at the cellular level, an absentee landlord that allows gene activity to go awry, according to a study published this week.
In experiments on mouse embryonic stem cells, Harvard Medical School researchers report in the journal Cell that a multitasking protein called SIRT1 that normally acts as guardian of the genome gets called away to fix damaged DNA, a chore that increases with age. When the protein abandons its normal post to work as a genetic handyman, order unravels. Inactive genes that are normally under its careful watch begin to flip on.
Knowing how that happens may open the way to stopping or slowing it, said David Sinclair, a Harvard Medical School biologist and author of the paper.
“What this paper actually implies is that aspects of aging may be reversible,” Sinclair said. “It sounds crazy, but in principle it should be possible to restore the youthful set of genes.”
What’s not yet clear is how much having the gene expression of one’s youth really matters. Scientists not involved in the study pointed out that it is not clear that keeping gene expression young is the key to a person actually staying young.
“The paper says you might be able to maintain or go back to a younger gene expression profile, but does that mean you will be younger?,” said Dr. Stephen Helfand, a professor in the department of molecular biology, cell biology, and biochemistry at Brown University. “You may have passed through that gate already.”
To understand SIRT1’s double duty in the cell, researchers inflicted DNA damage on mouse embryonic stem cells to emulate the effects of aging. They found that when SIRT1 was busy with repairs, genes that it had kept silent switched on.
What remains to be tested is whether shutting off those genes actually slows aging or has an effect on lifespan.
“That’s the rate-limiting question that is in the field right now, whether the changes in expression patterns are causally responsible for different aging outcomes,” said Thomas Johnson, a professor at the University of Colorado at Boulder who was not involved in the study.
