Featured Research

from universities, journals, and other organizations

Survival Mode That Protects Cells When Oxygen Is Low Also Slows Aging

Date:
April 21, 2009
Source:
University of Washington
Summary:
A biochemical pathway that keeps cells alive when oxygen is low has now been showed to play a role in longevity and resistance against some diseases of old age. The study was conducted in an animal model of aging, the nematode worm.

A biochemical pathway that helps keep cells alive when oxygen is low also plays a role in longevity and resistance against some diseases of old age, according to a report published in the journal Science.

Related Articles


A cell's protective reaction to a drop in oxygen is called the hypoxic response. Researchers at the University of Washington (UW) have found that nematode worms live longer if their genetic make-up permits their cells to turn on the hypoxic response under normal oxygen conditions.

Not only do these worms live longer, the researchers noted, their cells are relatively free from the toxic proteins that accumulate and clump together as an animal ages.

Dr. Matt Kaeberlein, UW assistant professor of pathology and the senior author on the study, said that defining cellular mechanisms that prevent accumulation of these proteins may point to new therapeutic targets for devastating diseases that often accompany old age in people. Toxic protein aggregations, he explained, are seen in the brain cells of those with Alzheimer's disease, Huntington's disease, and several other degenerative conditions that afflict the elderly.

The co-lead authors, Dr. Ranjana Mehta and Dr. Katy Steinkraus, uncovered the life-extending role of the hypoxic response while studying the mechanism by which dietary restriction slows aging in nematodes. Dietary restriction has been shown to increase life span in many different organisms, including worms, flies and mice. Kaeberlein's group had previously found that dietary restriction also protects against toxic protein aggregation in nematode models of Huntington's and Alzheimer's diseases. To their surprise, however, genetic experiments mapped the hypoxic response to a previously unknown longevity pathway, different from dietary restriction.

"The research findings suggest that the hypoxic response promotes longevity and reduces the accumulation of toxic proteins by a mechanism that is distinct from both dietary restriction and insulin-like signaling. It appears to be an alternative pathway," Kaeberlein said. "However, we don't know if future studies might reveal that all of these different genetic pathways converge somewhere down the line into a common mechanism for delaying the effects of age."

The key factor that controls the hypoxic response is called HIF. HIF is regulated by another protein called VHL-1, which tags HIF to be destroyed by a cellular machine called the proteasome. Destruction of HIF by VHL-1 keeps the hypoxic response "off" when oxygen is present. The UW researchers bred worms that could not produce VHL-1, leading to persistence of HIF even in the presence of high oxygen levels. They found that these worms, which were able to turn on the hypoxic response under normal oxygen conditions, lived about 30 percent longer than worms whose cells made VHL-1.

They also found that animals lacking VHL-1 were resistant to the toxic proteins known to cause Alzheimer's and Huntington's diseases, and that their cells accumulated less of an age-pigment called lipofuscin. Lipofuscin is thought to be one indicator of an animal's health during aging. According to Kaeberlein, "These observations may suggest that the hypoxic response not only increases life span, but also lengthens health span and protects against the molecular processes that lead to neurodegenerative diseases in people." Health span refers to the period of an organism's life that is relatively free of disease.

The authors note that the hypoxic response, including HIF and VHL-1, is very well conserved in organisms from nematodes to humans, raising the possibility that modulating HIF activity may be useful for treating some age-associated diseases, and perhaps even slowing aging, in people. Kaeberlein cautions, however, that "mutation of VHL-1 is associated with a variety of tumors, and any therapies targeted toward activation of HIF would most likely need to be specific for cells that are not rapidly dividing, such as brain cells or muscle cells."

"What we're focused on now," says Mehta, "is figuring out how HIF is protecting the animals from aging." In both worms and people, HIF regulates the activity of several factors involved in growth and resistance to stress. "One or more of these factors must be the key."

Kaeberlein agrees. "This is a completely new pathway for aging and age-associated disease. If we can understand at a very detailed level how HIF is slowing aging, we may be able to use that information to develop effective therapies for treating age-associated diseases in people."

The researchers on the study  in addition to Kaeberlein, Mehta, and Steinkraus, were George Sutphin, Fresnida J. Ramos, Lara S. Shmieh, Alexander Huh, Christina Davis, and Devon Chandler-Brown, all from the UW Department of Pathology or the UW Molecular and Cellular Biology Program.

The research was supported by the Alzheimer's Association, the Glenn Foundation, the American Federation for Aging Research, the National Institutes of Health, and the Hereditary Disease Foundation. Kaeberlein is an Ellison Medical Foundation New Scholar in Aging.


Story Source:

The above story is based on materials provided by University of Washington. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ranjana Mehta, Katherine A. Steinkraus, George L. Sutphin, Fresnida J. Ramos, Lara S. Shamieh, Alexander Huh, Christina Davis, Devon Chandler-Brown, and Matt Kaeberlein. Proteasomal Regulation of the Hypoxic Response Modulates Aging in C. elegans. Science, 2009; DOI: 10.1126/science.1173507

Cite This Page:

University of Washington. "Survival Mode That Protects Cells When Oxygen Is Low Also Slows Aging." ScienceDaily. ScienceDaily, 21 April 2009. <www.sciencedaily.com/releases/2009/04/090416144514.htm>.
University of Washington. (2009, April 21). Survival Mode That Protects Cells When Oxygen Is Low Also Slows Aging. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2009/04/090416144514.htm
University of Washington. "Survival Mode That Protects Cells When Oxygen Is Low Also Slows Aging." ScienceDaily. www.sciencedaily.com/releases/2009/04/090416144514.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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