Featured Research

from universities, journals, and other organizations

Certain proteins extend life span in worms by 30 percent

Date:
June 17, 2010
Source:
Stanford University Medical Center
Summary:
Researchers have identified a new group of proteins involved in determining the life span of laboratory roundworms. Blocking the expression of one member of the group can extend the worm's life span by up to 30 percent. Because the proteins work in the worms' reproductive systems, the research represents yet another intriguing link between longevity and fertility.

A roundworm.
Credit: iStockphoto/Nancy Nehring

Researchers at the Stanford University School of Medicine have identified a new group of proteins involved in determining the life span of laboratory roundworms. Blocking the expression of one member of the group can extend the worm's life span by up to 30 percent. Because the proteins work in the worms' reproductive systems, the research represents yet another intriguing link between longevity and fertility.

In particular, the researchers showed that the proteins are involved in epigenetics -- a phenomenon in which chemical modifications to DNA and the proteins around it affect how it is packaged and expressed in a cell. Although an organism can't change the DNA sequence of the genes it has inherited, epigenetic changes allow it to silence or tweak their expression in response to environmental or other external cues.

"We've shown here that an epigenetic change can affect the life span of an organism," said Anne Brunet, PhD, assistant professor of genetics, "but only within the context of an intact reproductive system." Brunet is the senior author of the study, which will be published online June 16 in Nature.

Roundworms, also known as Caenorhabditis elegans, are a popular laboratory animal. They are easy to care for, and their approximately four-week life span makes them good models for longevity studies. For technical reasons, though, most longevity researchers have conducted their experiments on sterile worms.

Brunet and graduate student Eric Greer wanted to explore the effect of epigenetic changes on longevity. But they wondered if using fertile worms might be more appropriate for their studies. After all, other studies of the worms have suggested that fertility is at least indirectly linked to longevity.

Greer, who is the lead author of the study, used a technique called RNA interference in fertile worms to methodically block the expression -- one by one -- of genes known to affect a cell's epigenetic status. He identified a number of genes that, when inhibited, caused the worms to live up to 30 percent longer than normal.

The gene with the most pronounced effect, Ash-2, makes a protein that functions as a methyltransferase -- meaning it works together with other proteins to add a chemical tag called a methyl group to a component of a cell's DNA packaging machinery, which is known as a histone. The presence or absence of this tag affects whether the DNA remains wound up tightly like thread on a spool, or unfurls to allow its genes to be expressed.

Inhibiting Ash-2 activity reduces the number of methyl tags on the histone, which keeps the DNA inaccessible and somehow extends the animal's life by as much as 30 percent. Conversely, the researchers found, blocking the expression of a protein called Rbr-2 taxed with removing the tag -- a demethylase -- shortened the worm's life span by about 15 to 25 percent. Worms in which the expression of both proteins were blocked had slightly shortened lives.

Clearly the levels of methylation on that particular spot on the histone are important to longevity. But why? And how are they calibrated?

The researchers found that Ash-2 is highly expressed in the germline, or reproductive cells, as well as in newly formed eggs. These cells also had high levels of the methyl tag. When Greer blocked the expression of Ash-2 in worms that lacked normal reproductive cells, he found that this no longer extended worm life span, suggesting that an intact germline is necessary for Ash-2 to regulate longevity.

Further investigation showed that Ash-2 activity affects the expression of several genes specific to germline cells, including a group previously shown to affect adult life span. Blocking Ash-2 expression only in germline cells, but not in the rest of the worm's body, still extended its life span, as did expressing excess amounts of the tag-removal protein Rbr-2 in the germline. Finally, another series of experiments showed that the presence of mature eggs is required for Ash-2 knockdown to have an effect.

"We still don't know exactly how this works mechanistically," said Brunet, "but we've shown that the presence of the germline is absolutely essential for this longevity extension to happen."

In the future the researchers plan to monitor the methylation status of the histone during the animal's life span. Because epigenetic changes are reversible, it's likely they'll see a natural ebb and flow as the worm ages. They'd also like to examine the effect of environmental situations known to affect longevity, such as calorie restriction, on the tagged histone.

"Aging is a very plastic process," said Brunet, who cautioned that it's possible that Ash-2 also works elsewhere in the worm. "This tagging doesn't affect reproduction directly, but it somehow talks to the rest of the body to affect the whole organism." Perhaps, they speculate, the genes activated by the loss of Ash-2 work together with other factors produced by mature eggs to lengthen the animal's life.

"It makes a sort of sense that the reproductive system would be involved in life span, since that is really the only 'immortal' part of an organism," said Brunet. "In that context, the body is just the mortal envelope."

In addition to Greer and Brunet, other Stanford researchers involved in the study include assistant professor Or Gozani, PhD; postdoctoral scholars Travis Maures, PhD, Erin Green, PhD, and Geraldine Maro, PhD; graduate students Dena Leeman, Shuo Han and Max Banko; and undergraduate student Anna Hauswirth. The research was supported by the National Institutes of Health, the Human Frontier Science Program and a Searle Scholar Award.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. The original article was written by Krista Conger. Note: Materials may be edited for content and length.


Journal Reference:

  1. Eric L. Greer, Travis J. Maures, Anna G. Hauswirth, Erin M. Green, Dena S. Leeman, Gιraldine S. Maro, Shuo Han, Max R. Banko, Or Gozani & Anne Brunet. Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature, June 16, 2010 DOI: 10.1038/nature09195

Cite This Page:

Stanford University Medical Center. "Certain proteins extend life span in worms by 30 percent." ScienceDaily. ScienceDaily, 17 June 2010. <www.sciencedaily.com/releases/2010/06/100616133319.htm>.
Stanford University Medical Center. (2010, June 17). Certain proteins extend life span in worms by 30 percent. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2010/06/100616133319.htm
Stanford University Medical Center. "Certain proteins extend life span in worms by 30 percent." ScienceDaily. www.sciencedaily.com/releases/2010/06/100616133319.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) — Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) — NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com
How to Master Motherhood With the Best Work/Life Balance

How to Master Motherhood With the Best Work/Life Balance

TheStreet (Apr. 22, 2014) — In the U.S., there are more than 11 million couples trying to conceive at any given time. From helping celebrity moms like Bethanny Frankel to ordinary soon-to-be-moms, TV personality and parenting expert, Rosie Pope, gives you the inside scoop on mastering motherhood. London-born entrepreneur Pope is the creative force behind Rosie Pope Maternity and MomPrep. She explains why being an entrepreneur offers the best life balance for her and tips for all types of moms. Video provided by TheStreet
Powered by NewsLook.com
Catching More Than Fish: Ugandan Town Crippled by AIDS

Catching More Than Fish: Ugandan Town Crippled by AIDS

AFP (Apr. 22, 2014) — The village of Kasensero on the shores of Lake Victoria was where HIV-AIDS was first discovered in Uganda. Its transient population of fishermen and sex workers means the nationwide programme to combat the virus has had little impact. Duration: 02:30 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins