Sirtuin protein discovery opens door to potential 'molecular fountain of youth'
A new study led by researchers at the University of California, Berkeley, represents a major advance in the understanding of the molecular mechanisms behind aging while providing new hope for the development of targeted treatments for age-related degenerative diseases.
Researchers were able to turn back the molecular clock by infusing the blood stem cells of old mice with a longevity gene and rejuvenating the aged stem cells' regenerative potential. The findings will be published online Thursday, Jan. 31, in the journal Cell Reports.
The biologists found that SIRT3, one among a class of proteins known as sirtuins, plays an important role in helping aged blood stem cells cope with stress. When they infused the blood stem cells of old mice with SIRT3, the treatment boosted the formation of new blood cells, evidence of a reversal in the age-related decline in the old stem cells' function.
"We already know that sirtuins regulate aging, but our study is really the first one demonstrating that sirtuins can reverse aging-associated degeneration, and I think that's very exciting," said study principal investigator Danica Chen, UC Berkeley assistant professor of nutritional science and toxicology. "This opens the door to potential treatments for age-related degenerative diseases."
Chen noted that over the past 10 to 20 years, there have been breakthroughs in scientists' understanding of aging. Instead of an uncontrolled, random process, aging is now considered as highly regulated as development, opening it up to possible manipulation.
"A molecular fountain of youth"
"Studies have already shown that even a single gene mutation can lead to lifespan extension," said Chen. "The question is whether we can understand the process well enough so that we can actually develop a molecular fountain of youth. Can we actually reverse aging? This is something we're hoping to understand and accomplish."
Chen worked with David Scadden, director of the Center for Regenerative Medicine at Massachusetts General Hospital and co-director of the Harvard Stem Cell Institute.
Sirtuins have taken the spotlight in this quest as the importance of this family of proteins to the aging process becomes increasingly clear. Notably, SIRT3 is found in a cell's mitochondria, a cell compartment that helps control growth and death, and previous studies have shown that the SIRT3 gene is activated during calorie restriction, which has been shown to extend lifespan in various species.
To gauge the effects of aging, the researchers studied the function of adult stem cells, which are responsible for maintaining and repairing tissue; it is a function that breaks down with age. They focused on hematopoietic, or blood, stem cells because of their ability to completely reconstitute the blood system, the capability that underlies successful bone marrow transplantation.
The researchers first observed the blood system of mice that had the gene for SIRT3 disabled. Surprisingly, among young mice, the absence of SIRT3 made no difference. It was only when time crept up on the mice that things changed. By the ripe old age of two, the SIRT3-deficient mice had significantly fewer blood stem cells and decreased ability to regenerate new blood cells compared with regular mice of the same age.
What is behind the age gap? It appears that in young cells, the blood stem cells are functioning well and have relatively low levels of oxidative stress, which is the burden on the body that results from the harmful byproducts of metabolism. At this youthful stage, the body's normal antioxidant defenses can easily deal with the low stress levels, so differences in SIRT3 are less important.
"When we get older, our system doesn't work as well, and we either generate more oxidative stress or we can't remove it as well, so levels build up," said Chen. "Under this condition, our normal antioxidative system can't take care of us, so that's when we need SIRT3 to kick in to boost the antioxidant system. However, SIRT3 levels also drop with age, so over time, the system is overwhelmed."
Old mice, new blood
To see if boosting SIRT3 levels could make a difference, the researchers increased the levels of SIRT3 in the blood stem cells of aged mice. That experiment rejuvenated the aged blood stem cells, leading to improved production of blood cells.
It remains to be seen whether over-expression of SIRT3 can actually prolong life, but Chen pointed out that extending lifespan is not the only goal for this area of research. "A major goal of the aging field is to utilize knowledge of genetic regulation to treat age-related diseases," she said.
Study co-lead author Katharine Brown, who conducted the research as a UC Berkeley Ph.D. student in Chen's lab, said SIRT3 has some potential in this regard.
"Other researchers have demonstrated that SIRT3 acts as a tumor suppressor," said Brown. "This is promising because, ideally, one would want a rejuvenative therapy where you could increase a protein's expression without increasing the risk of diseases like cancer."
Journal reference: Cell Reports
Provided by University of California - Berkeley
- Scientists identify gene that exacerbates risk factors for heart disease and diabetes Aug 18, 2011 | not rated yet | 0
- Scientists ferret out a key pathway for aging Nov 18, 2010 | not rated yet | 0
- Scientists ID key protein that links dietary restriction with healthy hearing, aging Dec 16, 2010 | not rated yet | 0
- Scientists identify key protein in energy regulation Mar 03, 2010 | not rated yet | 0
- Aging stem cells in mice may hold answers to diseases of the aged Jun 06, 2007 | not rated yet | 0
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
9 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 3 hours ago | 5 / 5 (1) | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 4 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 4 hours ago | 4.5 / 5 (2) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 7 hours ago | not rated yet | 0
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research 23 hours ago | 5 / 5 (2) | 0 |
7 minutes ago | not rated yet | 0
17 minutes ago | not rated yet | 0
17 minutes ago | not rated yet | 0
Variation in the gene MUC5B among patients with idiopathic pulmonary fibrosis was associated with improved survival, according to a study published online by JAMA. The study is being released early online to coincide with i ...
42 minutes ago | not rated yet | 0
As many as 35 percent of Mexican young adults may have a genetic predisposition for obesity, said a University of Illinois scientist who conducted a study at the Universidad Autónoma de San Luis Potosί.
44 minutes ago | not rated yet | 0
A federal court in San Francisco Tuesday struck down Arizona's ban on abortions after 20 weeks of pregnancy.
7 minutes ago | not rated yet | 0