Navigation Links
Elderly mice yield clues to the process of growing old

Delving deep into the molecular subtleties of a strain of mice engineered to age rapidly, scientists have found that an accumulation of genetic mutations prompts a cascade of programmed cell death that seems to underpin the aging process.

Writing today (July 15, 2005) in the journal Science, a team of scientists led by University of Wisconsin-Madison geneticist Tomas A. Prolla describes a series of experiments in mutant and normal mice that peel away some of the root secrets of mammalian aging.

Growing old, according to the new study, occurs, in part, as mutations build up in the DNA of energy-generating mitochondria, triggering the death of critical cells that lead to such things as hair and weight loss, hearing and vision impairment, loss of muscle mass, weakened bones and fewer circulating red blood cells. Mitochondria are structures within cells that provide energy for cells to move, divide, contract and secrete products vital for the health of organisms.

"We think that the key to what is happening in aging is that as (genetic) mutations or DNA damage accumulates, critical cells die," says Prolla. "These experiments favor a major role for programmed cell death in aging."

If true, the new insights may one day lead to opportunities to stave off old age through drugs that could prevent the gathering of genetic defects in mitochondrial DNA, genetic material that resides outside of the nucleus of a cell and that helps power critical cell processes.

Such insight could also lead to strategies to restore some functions such as hearing by protecting mitochondrial DNA from naturally occurring mutations.

Using mice genetically altered to have a deficiency in a protein that proofreads mitochondrial DNA and thus accumulate genetic mutations at a higher rate than unaltered mice, the group led by Prolla found evidence that programmed cell death, known as apoptosis, was greatly accelerated. The altered mice exhibited obvious hallma rks of aging -- including graying, hair loss and atrophied muscle and bone -- at a pace much faster than the typical laboratory mouse.

"It's like a broken spellchecker," says Prolla. "By introducing a malfunction in the (genetic) proofreading domain, these mutations accumulate much more rapidly."

The new work lends support to one of the two leading theories of how animals, including humans, grow old and die. It supports the theory that apoptosis or programmed cell death underpins aging. A competing theory holds that oxidative stress -- the body's reaction to oxygen and the production of reactive, cell-damaging molecules known as free radicals -- is responsible for the aging process.

According to the new Science report, markers of oxidative stress did not parallel the accumulation of mitochondrial genetic mutations. Instead, the group found evidence that indicated accelerated cell death, especially in tissues characterized by rapid turnover of cells, occurred as mutations mounted in the mitochondrial DNA.

"We found no evidence of oxidative stress," Prolla explains. In fact, the team noted less oxidative stress in some tissues - the liver, for example - which suggests that accumulated genetic mutations in mitochondria slow metabolism. In turn, that change prompts cells to produce fewer of the reactive free radical molecules.

The symptoms of aging become pronounced with the loss of some critical cells, notably adult stem cells from some tissues and that are essential for replacing cells that die. "If these stem cells are lost, tissue structure and the ability of tissue to regenerate are impaired," Prolla explains. "We have observed that in tissues like bone marrow, intestine and hair follicles."

The altered mice used in the study were created by manipulating mouse embryonic stem cells to produce mice with the defective DNA proofreading protein. The mice develop normally, but age rapidly and develop such things as age rela ted heart dysfunction, hair loss, loss of immune cells, anemia, and loss of male germ cells that lead to reduced sperm production and infertility.

Intriguingly, the mice develop symptoms of old age, notably gray hair and hair loss, more commonly seen in humans than mice.

Prolla suggests that new studies of mice engineered to have fewer than normal mitochondrial DNA defects or improved mitochondrial function may pave the way for strategies to retard aging. "The idea would be to reduce the level of cell death and improve function. If that pans out, then we can begin to think about pharmaceutical interventions to retard aging by preserving mitochondrial function."


'"/>

Source:University of Wisconsin-Madison


Related biology news :

1. FDA Warns About Antipsychotic Drugs and Elderly
2. Elderly spinal cord injuries increase five-fold in 30 years, Jefferson neurosurgeons find
3. Genome-wide mouse study yields link to human leukemia
4. Microbial fuel cell: High yield hydrogen source and wastewater cleaner
5. Insight into DNAs weakest links may yield clues to cancer biology
6. Marine sponge yields nanoscale secrets
7. New understanding of cell movement may yield ways to brake cancers spread
8. Small worm yields big clue on muscle receptor action
9. Modified collagen could yield important medical applications
10. Organic farms produce same yields as conventional farms
11. Weight control protein may yield antiobesity drugs
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based and Touchless), Product ... by MarketsandMarkets, the market is expected to be worth USD 18.98 billion by ... Continue Reading ... ...      (Logo: http://photos.prnewswire.com/prnh/20160303/792302) ...
(Date:3/22/2017)... 2017   Neurotechnology , a provider of ... announced the release of the SentiVeillance 6.0 ... facial recognition using up to 10 surveillance, security ... The new version uses deep neural-network-based facial detection ... utilizes a Graphing Processing Unit (GPU) for enhanced ...
Breaking Biology News(10 mins):
(Date:4/27/2017)... ... April 27, 2017 , ... This month Quorum ... solution that simplifies research studies, accelerates study startup, and improves participant engagement. Developed ... is the first and only IRB-integrated eConsent solution . , “Our mission ...
(Date:4/27/2017)... (PRWEB) , ... April 27, 2017 , ... ... a practicing internist, who will review how testing for 1,25-Dihydroxyvitamin D can enhance ... ordering of 25-OH-vitamin D and 1,25 dihydroxyvitamin D. , Dr. Gregory Plotnikoff, senior ...
(Date:4/27/2017)... ... April 27, 2017 , ... ... name change to Fluence Analytics. , Fluence Analytics provides proprietary hardware ... biopharmaceutical manufacturing processes and R&D applications. The company’s patented technologies improve production ...
(Date:4/27/2017)... (PRWEB) , ... April 27, 2017 , ... ... the 2017 Borlaug CAST Communication Award goes to Jayson Lusk, a consummate communicator ... forms of media to advocate for science, as he explains how innovation and ...
Breaking Biology Technology: