Gene May Hold Anti-Aging Secret

Fancy procedures like Botox, face lifts, and microdermabrasion are among the many tricks that can give aging skin a mask of youth. But Harvard Medical School researchers may have found a gene that can actually hold back the clock.

If the quantity of a protein that regulates gene expression and fixes damaged cells is increased, genes may be less likely to deteriorate, according to the study. Cells that remain in better condition for longer age more slowly, theoretically allowing organisms to remain younger longer.

“People may have an extended lifespan,” said Raul Mostoslavsky, a researcher at Harvard-affiliated Mass. General Hospital who worked on the study.

The protein, produced by a longevity gene called SIRT1, is known to perform two main jobs in yeast cells, according to Philipp Oberdoerffer, a pathologist at Harvard Medical School and the study’s lead author. He said that one job is to regulate certain gene, and another is to fix damaged areas of a cell.

“You can’t wait for a bunch of proteins [to get to the damaged area],” so the protein is “recruited from its normal site to fix the damage, and then once it is done it goes back to its site,” Oberdoerffer said.

While the protein is fixing the damaged cells, the genes in the protein’s normal site go unregulated. More problematically, when a cell is permanently damaged, the protein is permanently engaged at the place of the damage in a futile attempt to fix the problem. As a result, the protein never returns to its normal site.

Without the protein to regulate the genes, those that should not be expressed are activated and others that should be expressed are not.

“All genes have the same material but only parts of the material are expressed,” Oberdoerffer said. When different parts of the cell are “turned on,” the cell performs a different function.

“Every cell type expresses a distinct set of genes so that way you make one cell a kidney gene, one a brain cell,” Oberdoerffer added. “Every cell and every organ in your body has certain things to do, and if you mess around with that—[like if] your muscle cells express[es] a brain gene—then you can imagine that clearly your cell doesn’t function property anymore.”

Over time, as cells become worn out and become permanently damaged, more proteins are called away from their normal sites, leading more gene expression to go awry. This trend is part of the deterioration associated with aging.

“To prove that SIRT1 has a direct role in lifespan you will need to generate a mouse where you over-express these proteins...and you look to see whether the mouse has a longer lifespan,” Mostoslavsky said. “This has not been done yet, but in lower level organisms it has been show that when you increase genomic integrity you increase life.”

Oberdoerffer’s study extended the previous research on the protein—which had been conducted on yeast—to mice, which is a more advanced organism. Because the researchers found that the protein played similar roles in mice, their study suggests that it might also do so in humans.

While a genetic treatment for aging—such as an anti-aging pill—is not currently on the horizon, Mostoslavsky said that “if someone does this experiment and proves that the mice are healither and live longer without serious secondary consequences, then...it is safe to say that having these mice will prove a principle that humans could be justified” in seeking an anti-aging elixir.

The study was performed in the lab of David A. Sinclair of Harvard Medical School, who has done much work with the protein, SIRT1, and who co-authored the study.