Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Muscling toward a longer life: Genetic aging pathway identified in flies

18.10.2011
Researchers at Emory University School of Medicine have identified a set of genes that act in muscles to modulate aging and resistance to stress in fruit flies.

Scientists have previously found mutations that extend fruit fly lifespan, but this group of genes is distinct because it acts specifically in muscles. The findings could help doctors better understand and treat muscle degeneration in human aging.

The results were published online this week by the journal Developmental Cell.

The senior author is Subhabrata Sanyal, PhD, assistant professor of cell biology at Emory University School of Medicine. The first author of the paper is postdoc Alysia Vrailas-Mortimer. Collaborators from Howard University and the University of Athens contributed to the paper.

Vrailas-Mortimer, Sanyal and colleagues started investigating a pair of genes called "p38 MAP kinase" in fruit flies with the expectation that they could play a role in learning and memory. Along the way, they discovered that mutations in these genes speed up the process of aging and make the flies more sensitive to oxidative stress.

"It was really just dumb luck, because we found a mutant that had almost completely lost gene activity, but had enough activity to be born," Sanyal says.

If both genes are defective in the same fly, the flies die very early. They begin to develop motor problems, becoming unable to fly and climb, a few days after birth. The mutant flies are also more sensitive to heat, being deprived of food and water, and exposure to oxidative stress. The researchers could correct the effects of the mutations by restoring the genes' activity in muscles, but not nerve cells.

"The experiment that made us nervous was when we asked whether having more p38 could increase lifespan," Sanyal says. "You can make flies sick and shorten their lives in a hundred different ways easily, but finding one gene that makes a big change in lifespan is more significant."

Fruit flies normally live about fifty days in Sanyal's laboratory, depending on temperature and conditions. Some strains of fly that overproduce p38 MAP kinase live on average about 75 days, 50 percent longer than regular flies (green line in graph below). For this effect, it is sufficient that p38 is overproduced in muscles only.

Vrailas-Mortimer showed that a protein that protects cells against oxidative stress that is found in mitochondria, superoxide dismutase (MnSOD), is responsible for at least some of p38 MAP kinase's effects on aging. A third gene called MEF2 is also involved, in between p38 MAP kinase and MnSOD. Mitochondria are cells' miniature power plants and are more abundant in muscle.

Giving flies more MnSOD can restore a more normal lifespan to the p38 mutants. Other types of antioxidant enzymes don't rescue lifespan in flies with p38 mutations, the researchers found.

P38, MEF2 and MnSOD's action in muscles distinguishes them from a well-studied genetic circuit regulating aging in the worm C. elegans as well as flies and mice, which appears to work through insulin-like hormone responses in the brain and other tissues. Caloric restriction (consistently eating less), an established way of lengthening lifespan, acts through this insulin-like signaling pathway.

"It may be that oxidative stress is especially important in flies' muscles because flies' energy use is so high," Sanyal says. "The role oxidative stress plays in aging is well-known, so its involvement here was not a surprise. I think what's new here is finding a genetic pathway regulating aging that is specific to muscles and separate from insulin signaling."

Sanyal says he and his team plan to examine what kinds of dietary antioxidants can extend lifespan in flies without p38. They also plan to probe how caloric restriction interacts with p38 deficiency.

The research was supported by the National Institutes of Health and Emory's University Research Committee.

Reference:

A. Vrailas-Mortimer et al. A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function and lifespan in Drosophila. Dev Cell 21, 783-795 (2011).

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>