The Search for Immortality

Researchers may have found a protein that can extend the lifespan of mammals.

During ancient times, alchemists sought the elixir of life; a legendary potion believed to bestow eternal life upon its drinker. Alchemy has since given way to modern-day chemistry, but the quest for eternal life — or at least longer life — persists. While science has proven that the secret to longevity is not a potion, research has suggested that a protein might hold the answer.

A study published in Nature Journal of Science details the latest research on aging proteins, called sirtuins. A team led by Haim Cohen, a molecular biologist at Bar-llan University in Ramat-Gan Israel, has found that increased levels of SIRT6, one of the seven sirtuin proteins, can extend the maximum lifespan of male mice by about 15.8 percent.

Earlier research on the link between sirtuins and longevity focused on another member of the protein family. Researchers theorized that SIRT1, a protein in mammals closely related to a gene that promotes longevity in yeast, could extend the lifespan of mammals.

In 2001, a study published in Nature Journal of Science reported that SIRT1 increased the longevity in nematodes and fruit flies. The interest in this research was so high that in 2008, GlaxoSmirthKline, a drug company in London, invested $720 million in research targeting SIRT1 as a potential treatment for type 2 diabetes.

Later research found the SIRT1 study to be incorrect. The increased longevity was not an effect of SIRT1 but a result of unrelated mutations in the studied species.

PROTEINS WITH POTENTIAL

The hype surrounding SIRT1 was just the encouragement Cohen needed to begin his study of SIRT6.

“People were mostly interested in SIRT1,” Cohen said in Nature Journal of Science. “So I thought it might be better for us as a new lab to work on something that is less crowded.”

Previous studies had demonstrated that the aging process in mice lacking SIRT6 was accelerated. Cohen and his team decided to study the effects of higher than normal levels of SIRT6 in mice. While their results showed no effect on the maximum lifespan of the female mice, the male mice experienced an increase by as much as 15.8 percent.

The way in which SIRT6 functioned to increase the lifespan of the male mice is not yet clear.

Cohen thinks it has something to do with the effect of SIRT6 on a hormone which previous studies linked to aging.

“[We] have shown that SIRT6 decreases the hormone Insulin-like Growth Factor 1 (IGF-1) signaling,” Cohen said, assisted by Shoshanna Naiman, in an email interview.

“This hormone, while beneficial for growing in early years, might cause detrimental effects later in life, causing increased reactive oxygen species, DNA damage, and ultimately cell death,” Cohen said. “A reduction in this hormone is known to increase lifespan in a broad range of organisms, including yeast, worms, flies and mice. In addition, decreased IGF-1 levels were observed in aged humans as well, and centurions were shown to have decreased IGF-1 levels.”

MALE MIMICKERS

Another major focus of Cohen’s team is to discover why SIRT6 affected the lifespans in male mice, but in not female mice. Since the female mice used in the research usually live longer than females, Cohen speculates that the increased levels of SIRT6 allowed the male mice to catch up to the female mice.

“SIRT6 appears to have a ‘feminizing’ effect on the male gene expression profile, changing male gene expression to be similar to that of females,” Cohen said. “Several of these genes whose expression was altered could be longevity genes, which would normally only increase female lifespan. SIRT6 normalizes the levels of these longevity genes in males to be the same as females, thereby increasing male lifespan to be the same as females,” he said. “Therefore, we would only expect to see a difference in male lifespan, as females have no need of SIRT6 to ‘feminize’ their genes.”

Cohen explained that the male mice only experience femininity in their genes. He said he theorized that SIRT6 changes the levels of certain hormones in male mice to match those in female mice thus leveling the lifespans between the genders.

UNCERTAINTY OF SIRT6

Researchers continue to question the link between SIRT6 and the aging process. Newer studies have suggested that metabolic defects were the cause of the accelerated aging process that had earlier been attributed to a lack of SIRT6.

Other researchers attribute the increased lifespan of the male mice to an anti-cancer effect of SIRT6. Since the mice used in Cohen’s experiment tend to have tumors, their extended lifespan could have less to with an anti-aging effect and more to do with the anti-cancer effect of SIRT6 explained Richard Miller, a researcher of aging at University of Michigan in Ann Arbor, in Nature Journal of Science.

Cohen said he acknowledges the validity of this claim, but noted that his team did not find there to be a connection between the occurrences of tumors and the increased longevity in the male mice.

“It sounds like a worthy investment, but how long will it take before it can actually be used in humans?” said Samantha Flick, a senior in the College of Arts and Sciences. “Science is a very tricky field because there are so many steps between what a drug can do for mice and what it can do for humans.”

MULTI-PURPOSE PROTEIN

SIRT 6 is not the only sirtuin with demonstrated utility outside of the aging process. David Lombard, a mammalian sirtuin researcher at U of M, explained in Nature Journal of Science that all of the sirtuins have been shown to have salubrious effects on the ‘health span’ of mammals by multiple labs and in many different cases.

Although much of the attention and funding has surrounded the research of sirtuin application in the aging process, the usefulness of sirtuins does not end there. Much of the anti-aging research has shown that SIRT6 retains a possible application to cancer treatment research.

“There have been several papers published recently demonstrating that SIRT6 specifically inhibits or kills certain types of cancer cells,” Cohen said. “It is possible that under certain conditions which cause cancer—such as exposure to UV rays—SIRT6 will prevent the spread of cancer.”

This idea of a wider application of sirtuins is encouraging.

“I think that even if the scientists find out that the protein has no effect on the aging process, it is still worth studying for what it could do for cancer,” said Gabrielle Kovarie, a sophomore in the College of Arts and Sciences.