Biochemical clues to long lifespan revealed
Findings extend longevity research from yeast and worms to mammals
Researchers at Childrens Hospital Boston have discovered how two key cellular influences on lifespan work together, providing insights that may help reveal aging mechanisms in humans. The findings extend longevity research from yeast and worms into mammals, and suggest that longer life results, at least in part, from biochemical interactions that boost cells ability to resist environmental stresses while inhibiting them from committing suicide. The study appears in the February 19th Science Express, the online edition of the journal Science.
Previous studies in yeast and worms pinpointed a gene known as Sir2 as a key regulator of lifespan: deleting Sir2 limits lifespan, and extra copies lengthen it. Sir2 has a counterpart in mammals, but until now, very little was known about how it worked or what it had to do with aging. Working with mouse cells, researchers led by Anne Brunet, a postdoctoral fellow in neuroscience at Childrens Hospital who is now at Stanford University, discovered that Sir2 works by regulating a group of proteins known as FOXO transcription factors. FOXO proteins have also been linked with longevity; they control the expression of genes that regulate cell suicide, and also enable the cell to resist oxidative stress, or chemical stresses that can disrupt the cells DNA, or genetic blueprint.
"Aging involves damage to cells," says Dr. Michael E. Greenberg, director of Childrens Program in Neurobiology and senior investigator on the study. "If you reduce oxidative stress, you get less aging."
The Childrens team found that in the presence of oxidative stress, Sir2 promoted the ability of at least one FOXO protein, FOXO3, to provide stress resistance while suppressing its ability to induce cell death. In mammals, FOXO proteins confer stress resistance by triggering reactions that detoxify the damaging chemicals, known as free radicals. This leads to the repair of DNA damage while putting cell replication on hold, giving cells more time to perform the detoxification and repair process.
Greenberg, who holds a doctorate in biochemistry and is also a professor of neurology and neurobiology at Harvard Medical School, believes that bolstering a cells resistance to oxidative stress may help keep age-related disorders in check. He notes that the interaction between Sir2 and FOXO reduced the death of nerve cells, suggesting a possible strategy for reversing age-related nerve-cell degeneration, such as occurs in Alzheimers disease. The Sir2-FOXO interaction may also inhibit tumor formation, since DNA damage in cells can make them cancerous.
"If you have molecules that come together to mediate resistance to environmental stresses that cause aging, one might be able to come up with drugs that would affect this interaction and slow the aging process," Greenberg says.
The research was supported by the Ellison Medical Foundation, the National Institutes of Health, and the F.M. Kirby Foundation.
Childrens Hospital Boston is home to the worlds largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults for more than 130 years. More than 500 scientists, including seven members of the National Academy of Sciences, nine members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Childrens research community. Childrens is the primary pediatric teaching affiliate of Harvard Medical School.
Susan Craig | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...