Japanese scientists reverse aging in human cell

By altering the behavior of two genes responsible for the production of simple amino acids in human cells, scientists have gained a better understanding of how the process of ageing works, and how we could delay or perhaps even reverse it.

The team, led by Jun-Ichi Hayashi at the University of Tsukuba, targeted two genes that produce the amino acid glycine in the cell’s mitochondria, and figured out how to switch them on and off. By doing this, they could either accelerate the process of ageing within the cell, which caused significant defects to arise, or they could reverse the process of ageing, which restored the capacity for cellular respiration. Using this technique to produce more glycine in a 97-year-old cell line for 10 days, the researchers restored cellular respiration, effectively reversing the cell line’s age.

 The finding brings into question the popular, but more recently controversial, mitochondrial theory of ageing, which puts forward the notion that an accumulation of mutations in mitochondrial DNA leads to age-related defects in the mitochondria – often referred to as the cell’s powerhouses because they are responsible for energy production and cellular respiration. Defects in the cell’s mitochondria lead to damage in the DNA, and an accumulation of DNA damage is linked to age-related hair loss, weight loss, spine curvature, osteoporosis, and a decreased lifespan.

But is this theory accurate? The results of Hayashi’s study support an alternative theory to ageing, which proposes that age-associated mitochondrial defects are caused not by the accumulation of mutations in mitochondrial DNA, but by certain crucial genes being turned on and off as we get older.

The team worked with human fibroblast cell lines gathered from young people – from foetus-age to 12 years old – and the elderly, from 80 to 97 years old. They compared the capacity for cellular respiration in the young and old cells, and found that while the capacity was indeed lower in the cells of the elderly, there was almost no difference in the amount of DNA damage between the two. This calls into question the mitochondrial theory of ageing, the team reports in the journal Scientific Reports, and suggests instead that the age-related effects they were seeing were being caused by a process known as epigenetic regulation.

Epigenetic regulation describes the process where the physical structure of DNA – not the DNA sequence – is altered by the addition or subtraction of chemical structures or proteins, which is regulated by the turning on and off of certain genes. “Unlike mutations that damage that sequence, as in the other, aforementioned theory of ageing, epigenetic changes could possibly be reversed by genetically reprogramming cells to an embryonic stem cell-like state, effectively turning back the clock on ageing,” says Eric Mack at Gizmag.

Hayashi and his team supported this theory by showing that they could turn off the genes that regulate the production of glycine to achieve cellular ageing, or turn them on for the restoration of cellular respiration. This suggests, they say, that glycine treatment could effectively reverse the age-associated respiration defects present in their elderly human fibroblasts.

“Whether or not this process could be a potential fountain of youth for humans and not just human fibroblast cell lines still remains to be seen, with much more testing required,” Mack points out at Gizmag. “However, if the theory holds, glycine supplements could one day become a powerful tool for life extension.”

We’ll just have to wait and see. The faster we can solve the debate over how ageing actually works, the faster we can figure out how to delay it.

 

Source:  sciencedaily.com

1 Million Dollar Race For Cure To End Aging

The $1 Million Race For The Cure To End Aging

The $1 Million Race For The Cure To End Aging

 

The hypothesis is so absurd it seems as though it popped right off the pages of a science-fiction novel. Some scientists in Palo Alto are offering a $1 million prize to anyone who can end aging. “Based on the rapid rate of biomedical breakthroughs, we believe the question is not if we can crack the aging code, but when will it happen,” says director of the Palo Alto Longevity Prize Keith Powers.

It’s a fantastical idea: curing the one thing we will all surely die of if nothing else gets us before that. I sat down with Aubrey de Grey, the chief science officer of the SENS Research Foundation and co-author of “Ending Aging,” to discuss this very topic a few days back. According to him, ending aging comes with the promise to not just stop the hands of time, but to actually reverse the clock. We could, according to him, actually choose the age we’d like to exist at for the rest of our (unnatural?) lives. But we are far off from possibly seeing this happen in our lifetime, says de Grey. “With sufficient funding we have a 50/50 chance to getting this all working within the next 25 years, but it could also happen in the next 100,” he says.

If you ask Ray Kurzweil, life extension expert, futurist and part-time adviser to Google’s somewhat stealth Calico project, we’re actually tip-toeing upon the cusp of living forever. “We’ll get to a point about 15 years from now where we’re adding more than a year every year to your life expectancy,” he told the New York Times in early 2013. He also wrote in the book he co-authored with Terry Grossman, M.D., that “Immortality is within our grasp.” That’s a bit optimistic to de Grey (the two are good friends), but he’s not surprised this prize is coming out of Silicon Valley. “Things are changing here first. We have a high density of visionaries who like to think high.”

And he believes much of what Kurzweil says is true with the right funding. “Give me large amounts of money to get the research to happen faster,” says de Grey. He then points out that Google’s Calico funds are virtually unlimited.

Whether it’s 15, 25 or even 100 years off, we need to spur a revolution in aging research, according to Joon Yun, one of the sponsors of the prize. “The aim of the prize is to catalyze that revolution,” says Yun. His personal assistant actually came up with the initial idea. She just happens to be an acquaintance of Wendy Schmidt, wife of Google’s Eric Schmidt. But it was the passing of Yun’s 68-year-old father-in-law and some conversations with his friends that got him thinking about how to take on aging as a whole.

The Palo Alto Prize is also working with a number of angel investors, venture capital firms, corporate venture arms, institutions and private foundations within Silicon Valley to create health-related incentive prize competitions in the future. This first $1 million prize comes from Yun’s own pockets.

The initial prize will be divided into two $500,000 awards. Half a million dollars will go to the first team to demonstrate that it can restore heart rate variability (HRV) to that of a young adult. The other half of the $1 million will be awarded to the first team that can extend lifespan by 50 percent. So far 11 teams from all over the world have signed up for the challenge.

Source:  techcrunch.com

What makes human muscle age

Scientists discover clues on why human muscle ages:

 Scientists discover clues to what makes human muscle age


Scientists discover clues to what makes human muscle age

A study led by researchers at the University of California, Berkeley, has identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself.

Young, healthy muscle (top row) appears pink and red. In contrast, old muscle is marked by scarring and inflammation, as evidenced by the yellow and dark areas. This difference between old and young tissue occurs both in the muscle's normal state and after immobilization in a cast.
Young, healthy muscle (top row) appears pink and red. In contrast, old muscle is marked by scarring and inflammation, as evidenced by the yellow and dark areas. This difference between old and young tissue occurs both in the muscle’s normal state and after immobilization in a cast.  “Our study shows that the ability of old human muscle to be maintained and repaired by muscle stem cells can be restored to youthful vigor given the right mix of biochemical signals,” said Professor Irina Conboy, a faculty member in the graduate bioengineering program that is run jointly by UC Berkeley and UC San Francisco, and head of the research team conducting the study. “This provides promising new targets for forestalling the debilitating muscle atrophy that accompanies aging, and perhaps other tissue degenerative disorders as well.” Previous research in animal models led by Conboy, who is also an investigator at the Berkeley Stem Cell Center and at the California Institute for Quantitative Biosciences (QB3), revealed that the ability of adult stem cells to do their job of repairing and replacing damaged tissue is governed by the molecular signals they get from surrounding muscle tissue, and that those signals change with age in ways that preclude productive tissue repair. Those studies have also shown that the regenerative function in old stem cells can be revived given the appropriate biochemical signals. What was not clear until this new study was whether similar rules applied for humans. Unlike humans, laboratory animals are bred to have identical genes and are raised in similar environments, noted Conboy, who received a New Faculty Award from the California Institute of Regenerative Medicine (CIRM) that helped fund this research. Moreover, the typical human lifespan lasts seven to eight decades, while lab mice are reaching the end of their lives by age 2. Working in collaboration with Dr. Michael Kjaer and his research group at the Institute of Sports Medicine and Centre of Healthy Aging at the University of Copenhagen in Denmark, the UC Berkeley researchers compared samples of muscle tissue from nearly 30 healthy men who participated in an exercise physiology study. The young subjects ranged from age 21 to 24 and averaged 22.6 years of age, while the old study participants averaged 71.3 years, with a span of 68 to 74 years of age. In experiments conducted by Dr. Charlotte Suetta, a post-doctoral researcher in Kjaer’s lab, muscle biopsies were taken from the quadriceps of all the subjects at the beginning of the study. The men then had the leg from which the muscle tissue was taken immobilized in a cast for two weeks to simulate muscle atrophy. After the cast was removed, the study participants exercised with weights to regain muscle mass in their newly freed legs. Additional samples of muscle tissue for each subject were taken at three days and again at four weeks after cast removal, and then sent to UC Berkeley for analysis.
Human muscle stem cell regenerative activity is depicted in green and red. Stem cell responses were incapacitated when researchers inhibited the activation of key biochemical pathways, making the young muscle behave like old muscle. Old cells exhibited regenerative responses when properly triggered by experimental activation of biochemical signals.
Human muscle stem cell regenerative activity is depicted in green and red. Stem cell responses were incapacitated when researchers inhibited the activation of key biochemical pathways, making the young muscle behave like old muscle. Old cells exhibited regenerative responses when properly triggered by experimental activation of biochemical signals. Morgan Carlson and Michael Conboy, researchers at UC Berkeley, found that before the legs were immobilized, the adult stem cells responsible for muscle repair and regeneration were only half as numerous in the old muscle as they were in young tissue. That difference increased even more during the exercise phase, with younger tissue having four times more regenerative cells that were actively repairing worn tissue compared with the old muscle, in which muscle stem cells remained inactive. The researchers also observed that old muscle showed signs of inflammatory response and scar formation during immobility and again four weeks after the cast was removed. “Two weeks of immobilization only mildly affected young muscle, in terms of tissue maintenance and functionality, whereas old muscle began to atrophy and manifest signs of rapid tissue deterioration,” said Carlson, the study’s first author and a UC Berkeley post-doctoral scholar funded in part by CIRM. “The old muscle also didn’t recover as well with exercise. This emphasizes the importance of older populations staying active because the evidence is that for their muscle, long periods of disuse may irrevocably worsen the stem cells’ regenerative environment.” At the same time, the researchers warned that in the elderly, too rigorous an exercise program after immobility may also cause replacement of functional muscle by scarring and inflammation. “It’s like a Catch-22,” said Conboy. The researchers further examined the response of the human muscle to biochemical signals. They learned from previous studies that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell’s ability to divide. The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells’ capacity to effectively rebuild the body. This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue. MAP kinase (MAPK) is familiar to developmental biologists since it is an important enzyme for organ formation in such diverse species as nematodes, fruit flies and mice. For old human muscle, MAPK levels are low, so the Notch pathway is not activated and the stem cells no longer perform their muscle regeneration jobs properly, the researchers said. When levels of MAPK were experimentally inhibited, young human muscle was no longer able to regenerate. The reverse was true when the researchers cultured old human muscle in a solution where activation of MAPK had been forced. In that case, the regenerative ability of the old muscle was significantly enhanced. “The fact that this MAPK pathway has been conserved throughout evolution, from worms to flies to humans, shows that it is important,” said Conboy. “Now we know that it plays a key role in regulation and aging of human tissue regeneration. In practical terms, we now know that to enhance regeneration of old human muscle and restore tissue health, we can either target the MAPK or the Notch pathways. The ultimate goal, of course, is to move this research toward clinical trials.”