Joslin researchers discover new effect for insulin

Mar 20, 2008

Researchers at the Joslin Diabetes Center have shown that insulin has a previously unknown effect that plays a role in aging and lifespan, a finding that could ultimately provide a mechanism for gene manipulations that could help people live longer and healthier lives.

The paper, published in the March 21st issue of Cell, reports that insulin inhibits a master gene regulator protein known as SKN-1, and that increased SKN-1 activity increases lifespan. SKN-1 controls what is called the Phase 2 detoxification pathway, a network of genes that defends cells and tissue against oxidative stress – damage caused by elevated levels of free radicals (byproducts of metabolism) – and various environmental toxins. The new finding was demonstrated in experiments on the digestive system of C. elegans, a microscopic worm often used as a model organism.

“We’ve found something new that insulin does and it has to be considered when we think about how insulin is affecting our cells and bodies,” said Dr. T. Keith Blackwell, senior investigator at Joslin and author of the paper. “This has implications for basic biology since under some circumstances insulin may reduce defense against the damaging effects of oxidative stress more than we realize.”

The idea down the line is that fine-tuning the activity of SKN-1 may lead to increased resistance to chronic diseases and influence longevity, he said. The work could be important as it relates to diabetes and the many problems associated with the disease, particularly vascular and renal complications.

But, today’s finding may be most important for what it teaches about aging in general, he said.

“The major implication is that we have found something new that affects lifespan and aging, and an important new effect that insulin and/or a related hormone called insulin-like growth factor-1 may have in some tissues,” said Blackwell. “The implications go far beyond diabetes.”

It has been known since the 1990s that insulin inhibits a gene regulator protein known as FOXO, important in diabetes metabolism, tumor suppression and stem cell maintenance. FOXO controls a number of genes, including many involved in stress resistance. Studies in C. elegans showed that reduced insulin signaling boosted activity of a FOXO protein known as DAF-16, leading to greater stress resistance and longer life.

The new work places SKN-1 alongside FOXO as a second master gene regulator that is inhibited by insulin signaling and adds to the body of knowledge about insulin and its effects on gene pathways, stress resistance and aging. According to the paper, insulin’s effect on SKN-1 occurs independently of its effect on DAF-16.

“You can manipulate the expression of SKN-1 and the worms live longer,” said Blackwell, an Associate Professor of Pathology at Harvard Medical School and faculty member at the Harvard Stem Cell Institute.

The experiments will have to be repeated in mammals, where insulin and insulin-like growth factor-1 have a complex array of effects in different tissues. But, according to Blackwell, other findings in the C. elegans model have generally turned out to be applicable to mice and humans.

Blackwell’s lab at Joslin is focusing on mechanisms of free radical resistance and aging, and on gene regulation mechanisms in C. elegans stem cells with the idea of using this knowledge towards reprogramming human stem cells into insulin-producing cells.

Source: Joslin Diabetes Center

Explore further: Strategy proposed for preventing diseases of aging

add to favorites email to friend print save as pdf

Related Stories

How Kindle Unlimited compares with Scribd, Oyster

2 hours ago

Amazon is the latest—and largest—company to offer unlimited e-books for a monthly fee. Here's how Kindle Unlimited, which Amazon announced Friday, compares with rivals Scribd and Oyster.

NASA sees powerful thunderstorms in Tropical Storm Matmo

2 hours ago

Strong thunderstorms reaching toward the top of the troposphere circled Tropical Storm Matmo's center and appeared in a band of thunderstorms on the storm's southwestern quadrant. Infrared imagery from NASA's ...

ISS 'space truck' launch postponed: Arianespace

4 hours ago

The July 24 launch of a robot ship to deliver provisions to the International Space Station has been postponed "for a few days", space transport firm Arianespace said Friday.

Recommended for you

Strategy proposed for preventing diseases of aging

20 minutes ago

Medicine focuses almost entirely on fighting chronic diseases in a piecemeal fashion as symptoms develop. Instead, more efforts should be directed to promoting interventions that have the potential to prevent ...

Intestinal parasites are 'old friends,' researchers argue

3 hours ago

Intestinal parasites such as tapeworms, hookworms and a protist called Blastocystis can be beneficial to human health, according to a new paper that argues we should rethink our views of organisms that live off the human ...

Researchers unlock the protein puzzle

3 hours ago

By using brightly hued dyes, George Mason University researchers discovered an innovative way to reveal where proteins touch each other, possibly leading to new treatments for cancer, arthritis, heart disease and even lung ...

User comments : 0