Featured Research

from universities, journals, and other organizations

Why aging may predispose people to fibrotic diseases

Date:
April 9, 2014
Source:
University of Alabama at Birmingham
Summary:
A new study highlights why fibrotic diseases — diseases that feature fibrosis or scarring of organ tissue — are typically associated with aging. Fibrosis, the formation of fibrous scar tissue in response to injury, is part of the normal healing process. In the young, scars resolve over time and are replaced by new tissue. In older subjects, the scars do not resolve or fade, and scar tissue can build up. In organs such as the heart, lungs, kidneys or liver, the buildup of scar tissue can interfere with normal function, with potentially devastating results.

A new study from the University of Alabama at Birmingham highlights why fibrotic diseases -- diseases that feature fibrosis or scarring of organ tissue -- are typically associated with aging.

Fibrosis, the formation of fibrous scar tissue in response to injury, is part of the normal healing process. In young animals or people, scars resolve or fade away over time and are replaced by newly grown healthy tissue. In older subjects, the scars do not resolve or fade, and scar tissue can build up. In organs such as the heart, lungs, kidneys or liver, the buildup of scar tissue can interfere with normal function, with potentially devastating results.

In findings published April 9 in Science Translational Medicine, the UAB team describes the mechanism that contributes to persistent fibrosis in the aged, and suggests targets that may help reverse the buildup of scar tissue.

"The findings presented here represent the first understanding we have of why fibrosis is more prevalent in older individuals," said Victor J. Thannickal, M.D., professor and director of the Division of Pulmonary, Allergy and Critical Care Medicine at UAB and the study's senior author. "With a better understanding of the pathway that prevents the normal resolution of scar tissue in the elderly, we can look for new therapies that may help prevent or slow the progression of fibrotic diseases."

One fibrotic disease in particular is the focus of Thannickal's laboratory. Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with no effective treatment or cure. Often brought on by environmental triggers such as smoking, IPF usually worsens with age. Progressive scarring within the air sacs of the lungs blocks them from performing their function of exchanging oxygen for carbon dioxide. Patients in effect suffocate from within.

"In response to lung injury, cells called myofibroblasts are recruited to facilitate healing. An oxidant-generating enzyme, NADPH oxidase-4 (Nox4), promotes the formation of myofibroblasts. As normal healing proceeds and the myofibroblasts' job is completed, they undergo apoptosis, or programmed cell death, which allows the scar tissue to resolve and normal healing to occur," said Louise Hecker, Ph.D., assistant professor and first author of the study.

Hecker says the study shows that the ability to resolve scar tissue was markedly diminished in older mice. This inability to resolve fibrosis was attributed to myofibroblasts' becoming resistant to apoptosis and persisting within injured tissue. In older mice, this resistance to apoptosis is the result of a deficiency in activating the antioxidant response transcription factor, nuclear factor-like 2, or Nrf2. This imbalance between Nox4 and Nrf2 was observed in the animal model, as well as in human IPF fibroblasts and lung tissue.

"Fibrosis affects organ systems other than the lungs, and aging is often a risk factor for the disease and its progression," said Thannickal. "This research is exciting in that we now understand how age affects fibrosis, and we now have two targets to reduce or control fibrosis. We can look for ways to better activate or to boost Nrf2, or we can look for ways to inhibit Nox4 directly."

Hecker and Thannickal's team is developing novel drug candidates to target Nox4.

Human fibrotic disorders are estimated to contribute to 45 percent of deaths in the United States. IPF affects 200,000 people in the United States and 5 million worldwide.


Story Source:

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


Journal Reference:

  1. L. Hecker, N. J. Logsdon, D. Kurundkar, A. Kurundkar, K. Bernard, T. Hock, E. Meldrum, Y. Y. Sanders, V. J. Thannickal. Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox Imbalance. Science Translational Medicine, 2014; 6 (231): 231ra47 DOI: 10.1126/scitranslmed.3008182

Cite This Page:

University of Alabama at Birmingham. "Why aging may predispose people to fibrotic diseases." ScienceDaily. ScienceDaily, 9 April 2014. <www.sciencedaily.com/releases/2014/04/140409155714.htm>.
University of Alabama at Birmingham. (2014, April 9). Why aging may predispose people to fibrotic diseases. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2014/04/140409155714.htm
University of Alabama at Birmingham. "Why aging may predispose people to fibrotic diseases." ScienceDaily. www.sciencedaily.com/releases/2014/04/140409155714.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Nigeria Ups Ebola Stakes on 1st Death

Nigeria Ups Ebola Stakes on 1st Death

Reuters - Business Video Online (July 29, 2014) Nigerian authorities have shut and quarantined a Lagos hospital where a Liberian man died of the Ebola virus, the first recorded case of the highly-infectious disease in Africa's most populous economy. David Pollard reports Video provided by Reuters
Powered by NewsLook.com
Running 5 Minutes A Day Might Add Years To Your Life

Running 5 Minutes A Day Might Add Years To Your Life

Newsy (July 29, 2014) According to a new study, just five minutes of running or jogging a day could add years to your life. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Poses Little Threat To U.S.: CDC

Ebola Outbreak Poses Little Threat To U.S.: CDC

Newsy (July 29, 2014) The Ebola outbreak in West Africa poses little threat to Americans, according to officials with the Centers for Disease Control and Prevention. Video provided by Newsy
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