Featured Research

from universities, journals, and other organizations

Roadmap to metabolic reprogramming for aging

Date:
November 29, 2012
Source:
University of Wisconsin-Madison
Summary:
To survey previously uncharted territory, a team of researchers have created an "atlas" that maps more than 1,500 unique landmarks within mitochondria that could provide clues to the metabolic connections between caloric restriction and aging.

In efforts to understand what influences life span, cancer and aging, scientists are building road maps to navigate and learn about cells at the molecular level.

To survey previously uncharted territory, a team of researchers at UW-Madison has created an "atlas" that maps more than 1,500 unique landmarks within mitochondria that could provide clues to the metabolic connections between caloric restriction and aging.

The map, as well as the techniques used to create it, could lead to a better understanding of how cell metabolism is rewired in some cancers, age-related diseases and metabolic conditions such as diabetes.

"It's really a dynamic atlas for regulatory points in mitochondrial function -- there are many interesting avenues that other scientists can follow up on," says John Denu, University of Wisconsin-Madison professor of biomolecular chemistry and leader of the epigenetics theme at the Wisconsin Institute for Discovery (WID). "It could take years for researchers to understand what it all means, but at least now we have a list of the most important players."

In previous experiments, it's been shown that consuming less food increases the life span and health span in a range of organisms, from yeast and flies to mice and nonhuman primates. But pinpointing where and how caloric restriction affects cells at a molecular level remains the challenge.

So far, mitochondrial proteins, the molecules that command specific actions in the cell's powerhouse organelle, are at center stage of metabolic reprogramming.

Denu and colleagues conducted earlier research on the mitochondrial protein Sirt3, where they suggested a link between Sirt3 and the benefits of caloric restriction in situations such as the prevention of age-related hearing loss.

The new research, published in the Nov. 29 issue of the journal Molecular Cell, more broadly identifies pathways in mitochondria that could be behind the rewiring of metabolism. Their work uncovered regulatory processes that maintain mitochondrial health, control cells' ability to metabolize fat and amino acids, as well as stimulate antioxidant responses. This rewiring involves the addition or removal of two-carbon (acetylation) chemical groups within regulatory molecules called proteins.

In the study, scientists looked at liver tissue from groups of mice -- both with and without the ability to produce Sirt3. Some received a calorically restricted diet and some did not. After one year, they compared protein and acetylation changes among the groups of mice. They found Sirt3 was essential for many of the metabolic adaptations that occur during calorie restriction. These results suggest that therapies, including diet or drugs that enhance Sirt3 function, might provide novel interventions to fend off age-related illnesses.

Joshua Coon, professor of chemistry and biomolecular chemistry at UW-Madison and co-author of the paper, crafted a new technique to find these molecular sites. While the genome plays a key role in an organism's health, he points out that studying proteins -- the molecular machines that carry out an organism's original genetic instructions -- can be more accurate in revealing how a gene functions.

"We've taken dozens of primary tissues and profiled their protein content with depth to learn how they vary," Coon says. "With that information, we have direct knowledge at the molecular level of how an organism is dealing with adaption to diet, or potentially, a given disease state."

He says using mass spectrometry to look for acetylated proteins from tissue samples is a more fruitful approach to identifying relevant physiological changes. The study, he says, is one of the first of many that will create descriptive maps for other disease models.

To expand access to these enabling technologies across campus, Coon plans to launch the Wisconsin Center for Collaborative Proteomics in 2013. The center has received significant support from the UW and is pending further support via federal funding.


Story Source:

The above story is based on materials provided by University of Wisconsin-Madison. The original article was written by Marianne English. Note: Materials may be edited for content and length.


Journal Reference:

  1. Alexander S. Hebert, Kristin E. Dittenhafer-Reed, Wei Yu, Derek J. Bailey, Ebru Selin Selen, Melissa D. Boersma, Joshua J. Carson, Marco Tonelli, Allison J. Balloon, Alan J. Higbee, Michael S. Westphall, David J. Pagliarini, Tomas A. Prolla, Fariba Assadi-Porter, Sushmita Roy, John M. Denu, Joshua J. Coon. Calorie Restriction and SIRT3 Trigger Global Reprogramming of the Mitochondrial Protein Acetylome. Molecular Cell, 2012 DOI: 10.1016/j.molcel.2012.10.024

Cite This Page:

University of Wisconsin-Madison. "Roadmap to metabolic reprogramming for aging." ScienceDaily. ScienceDaily, 29 November 2012. <www.sciencedaily.com/releases/2012/11/121129130500.htm>.
University of Wisconsin-Madison. (2012, November 29). Roadmap to metabolic reprogramming for aging. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2012/11/121129130500.htm
University of Wisconsin-Madison. "Roadmap to metabolic reprogramming for aging." ScienceDaily. www.sciencedaily.com/releases/2012/11/121129130500.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 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