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

Scientists discover key driver of reversing aging process

A study tying the aging process to the deterioration of tightly packaged bundles of cellular DNA could lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer's disease, experts say.

A study tying the aging process to the deterioration of tightly packaged bundles of cellular DNA could lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer’s disease, experts say.

A study tying the aging process to the deterioration of tightly packaged bundles of cellular DNA could lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer’s disease, experts say. In the study, scientists at the Salk Institute and the Chinese Academy of Science found that the genetic mutations underlying Werner syndrome, a disorder that leads to premature aging and death, resulted in the deterioration of bundles of DNA known as heterochromatin.

The discovery, made possible through a combination of cutting-edge stem cell and gene-editing technologies, could lead to ways of countering age-related physiological declines by preventing or reversing damage to heterochromatin.

“Our findings show that the gene mutation that causes Werner syndrome results in the disorganization of heterochromatin, and that this disruption of normal DNA packaging is a key driver of aging,” says Juan Carlos Izpisua Belmonte, a senior author on the paper. “This has implications beyond Werner syndrome, as it identifies a central mechanism of aging–heterochromatin disorganization–which has been shown to be reversible.”

Werner syndrome is a genetic disorder that causes people to age more rapidly than normal. It affects around one in every 200,000 people in the United States. People with the disorder suffer age-related diseases early in life, including cataracts, type 2 diabetes, hardening of the arteries, osteoporosis and cancer, and most die in their late 40s or early 50s.

The disease is caused by a mutation to the Werner syndrome RecQ helicase-like gene, known as the WRN gene for short, which generates the WRN protein. Previous studies showed that the normal form of the protein is an enzyme that maintains the structure and integrity of a person’s DNA. When the protein is mutated in Werner syndrome it disrupts the replication and repair of DNA and the expression of genes, which was thought to cause premature aging. However, it was unclear exactly how the mutated WRN protein disrupted these critical cellular processes.

In their study, the Salk scientists sought to determine precisely how the mutated WRN protein causes so much cellular mayhem. To do this, they created a cellular model of Werner syndrome by using a cutting-edge gene-editing technology to delete WRN gene in human stem cells. This stem cell model of the disease gave the scientists the unprecedented ability to study rapidly aging cells in the laboratory. The resulting cells mimicked the genetic mutation seen in actual Werner syndrome patients, so the cells began to age more rapidly than normal. On closer examination, the scientists found that the deletion of the WRN gene also led to disruptions to the structure of heterochromatin, the tightly packed DNA found in a cell’s nucleus.

This bundling of DNA acts as a switchboard for controlling genes’ activity and directs a cell’s complex molecular machinery. On the outside of the heterochromatin bundles are chemical markers, known as epigenetic tags, which control the structure of the heterochromatin. For instance, alterations to these chemical switches can change the architecture of the heterochromatin, causing genes to be expressed or silenced.

The Salk researchers discovered that deletion of the WRN gene leads to heterochromatin disorganization, pointing to an important role for the WRN protein in maintaining heterochromatin. And, indeed, in further experiments, they showed that the protein interacts directly with molecular structures known to stabilize heterochromatin–revealing a kind of smoking gun that, for the first time, directly links mutated WRN protein to heterochromatin destabilization.

“Our study connects the dots between Werner syndrome and heterochromatin disorganization, outlining a molecular mechanism by which a genetic mutation leads to a general disruption of cellular processes by disrupting epigenetic regulation,” says Izpisua Belmonte. “More broadly, it suggests that accumulated alterations in the structure of heterochromatin may be a major underlying cause of cellular aging. This begs the question of whether we can reverse these alterations–like remodeling an old house or car–to prevent, or even reverse, age-related declines and diseases.”

Izpisua Belmonte added that more extensive studies will be needed to fully understand the role of heterochromatin disorganization in aging, including how it interacts with other cellular processes implicated in aging, such as shortening of the end of chromosomes, known as telomeres. In addition, the Izpisua Belmonte team is developing epigenetic editing technologies to reverse epigenetic alterations with a role in human aging and disease.


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

Protein could reverse the aging process

protein that could reverse the aging process

protein that could reverse the aging process

Researchers from the Harvard Stem Cell Institute (HSCI) have shown that injections of a protein dubbed GDF11, when administered to older mice, appear to cause a reversal of many signs of aging. Analysis showed that every major organ system tested displayed signs of improvement, with the protein even appearing to reverse some of the DNA damage which is synonymous with the aging process itself.

The protein GDF11 is found in humans as well as mice, and is now being considered for possible human testing due to its surprising and apparently regenerative properties.

A previous study had focused on examining the hearts of mice the equivalent of 70 human years old. The mice were regularly exposed to the blood of younger mice whose blood carried a higher concentration of GDF11. Ordinarily the hearts of older mice are enlarged and weakened, however results from the previous study displayed that, thanks to the GDF11 protein present in the blood of the younger mice, the hearts of the elderly mice reduced in size, making them appear younger and healthier. The changes were not purely aesthetic however, with the mice displaying an increased ability to exercise for prolonged periods of time.

The most recent set of experiments tested the protein in two ways. The first stage of the testing involved linking the circulatory systems of an older and a younger mouse through what is known as a parabiotic system. This allowed the protein-rich blood from the younger mouse to flow through the elder’s system continuously, maximizing the effect of the protein. The second method involved injecting the older mice with a concentrated dose of GDF11.

Results from the second study showed that the protein had positive effects reaching far beyond the heart. It was found that, having been exposed to increased levels of the protein, all organs examined by the researchers displayed a heightened level of function. Furthermore, whilst previous studies on the protein had focused on regenerating damaged muscle in mice, the most recent study focused on the repair of cells damaged by the aging process. The GDF11 protein was found to reverse some of this damage, allowing muscle to function as effectively as that of a much younger mouse.

Analysis of the brains of the older mice via MRI imaging displayed an increase in neural stem cells along with the development of blood cells in the brain. “There seems to be little question that, at least in animals, GDF11 has an amazing capacity to restore aging muscle and brain function,” states Dr. Doug Melton, co-chair of HSCI. The team believes that due to the increased blood flow exhibited in the brain of the elderly mice, it may be possible to reverse some of the cognitive effects of aging. The protein was also found to improve the olfactory system of older mice, greatly heightening their sense of smell.

In terms of human applications, it is hoped that a drug derived from GDF11 will lead to a cure for conditions such as diastolic heart failure. This condition is a defect which eventually causes one or more of the ventricles of the heart to deteriorate while attempting to fill the heart with blood, in order to pump it around the body. There is also a possibility that a GDF11-inspired drug could be used to combat Alzheimer’s, a condition synonymous with the aging process.

Looking to the future, the team will continue studies of the GDF11 protein, with a view to begin human medical trials within three to five years.


Source: w.gizmag.com