Reverse aging: Can science turn back the clock?

Reverse aging: Can science turn back the clock?

Sarah Yang-Berkeley on Friday, February 1, 2013 13:47
Source: futurity.org 

UC BERKELEY (US) — Researchers report they’ve made a major advance in understanding the molecular mechanisms behind aging.

"Studies have already shown that even a single gene mutation can lead to lifespan extension," says Danica 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." (Credit: "youth pill" via Shutterstock)

The team was 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 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,” says study principal investigator Danica Chen, an assistant professor of nutritional science and toxicology at the University of California, Berkeley.

“This opens the door to potential treatments for age-related degenerative diseases.”

Chen notes 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 highly regulated as development, opening it up to possible manipulation.

‘Molecular fountain of youth’

“Studies have already shown that even a single gene mutation can lead to lifespan extension,” says 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.”

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. The adult stem cells are responsible for maintaining and repairing tissue, 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 anti-oxidant 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,” says Chen. “Under this condition, our normal anti-oxidative system can’t take care of us, so that’s when we need SIRT3 to kick in to boost the anti-oxidant 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 says.

Study co-lead author Katharine Brown, who conducted the research as a student in Chen’s lab, says SIRT3 has some potential in this regard.

“Other researchers have demonstrated that SIRT3 acts as a tumor suppressor,” says 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.”

Researchers from the University of Toronto, Massachusetts General Hospital’s Center for Regenerative Medicine, and the Harvard Stem Cell Institute contributed to study, which is published in the journal Cell Reports.

The Searle Scholars Program, the National Institutes of Health, and the Siebel Stem Cell Institute partially funded the study.

Source: University of California, Berkeley

Straight from the Source

Read the original study

DOI: 10.1016/j.celrep.2013.01.005

Scientists find key to immortality for asexual worms

Scientists find key to immortality for asexual worms

By Kate Kelland

LONDON | Mon Feb 27, 2012 3:18pm EST
Source: reuters.com

mdc.helmholtz.de

(Reuters) - Who wants to live forever? Some flatworms do, even if it means no sex.

British scientists have found that a species of flatworm can overcome the process of ageing to become potentially immortal and say their work sheds light on possibilities of alleviating ageing and age-related characteristics in human cells.

In a study published in the Proceedings of the National Academy of Sciences journal on Monday the researchers found that the flatworms, known as planarian worms, can continuously maintain the length of a crucial part of their DNA, known as telomeres, during regeneration.

"Our data satisfy one of the predictions about what it would take for an animal to be potentially immortal," said Aziz Aboobaker, who led the research at Britain's University of Nottingham. "The next goals for us are to understand the mechanisms in more detail and to understand more about how you evolve an immortal animal."

Planarian worms have long fascinated scientists because they have an extraordinary ability to regenerate. A planarian worm split lengthwise or crosswise will regenerate into two separate living worms.

Aboobaker's team studied two types of planarian - those that reproduce sexually, like humans, and those that reproduce asexually by simply dividing in two.

Both types appear to regenerate indefinitely by growing new muscles, skin, guts and even entire brains again and again, Aboobaker explained in a statement about the work, but the asexual ones also renew their stocks of a key enzyme which may mean they can be immortal.

Scientists know that one of the key factors associated with ageing cells is telomere length. Telomeres are sections of DNA that cap the ends of chromosomes, protecting them from damage and the loss of cell functions linked to ageing. Shorter telomeres are thought to be an indicator of faster ageing.

Previous research -- which won the Nobel Prize for Medicine in 2009 -- has shown that telomeres can be maintained by the activity of an enzyme called telomerase.

In most sexually reproducing organisms the enzyme is most active during early development, but Aboobaker's team found that in the asexual worms, the planarian version of the enzyme is dramatically increased during regeneration - a factor that allows stem cells to maintain their telomeres as they divide to replace missing tissues.

Douglas Kell, chief executive of the Biotechnology and Biological Sciences Research Council which part-funded the study, described the finding as "exciting" and said it "contributes significantly to our fundamental understanding of some of the processes involved in ageing."

The work also "builds strong foundations for improving health and potentially longevity in other organisms, including humans," he said in a statement.

(Editing by Paul Casciato)