Researchers may have discovered fountain of youth by reversing aging in human cells

Japanese noriben, in the shape of mitochondria (Credit: University of Tsukuba)

Researchers in Japan have found that human aging may be able to be delayed or even reversed, at least at the most basic level of human cell lines. In the process, the scientists from the University of Tsukuba also found that regulation of two genes is related to how we age.

The new findings challenge one of the current popular theories of aging, that lays the blame for humans' inevitable downhill slide with mutations that accumulate in our mitochondrial DNA over time. Mitochondrion are sometimes likened to a cellular "furnace" that produces energy through cellular respiration. Damage to the mitochondrial DNA results in changes or mutations in the DNA sequence that build up and are associated with familiar signs of aging like hair loss, osteoporosis and, of course, reduced lifespan.

So goes the theory, at least. But the Tsukuba researchers suggest that something else may be going on within our cells. Their research indicates that the issue may not be that mitochondrial DNA become damaged, but rather that genes get turned "off" or "on" over time. Most intriguing, the team led by Professor Jun-Ichi Hayashi was able to flip the switches on a few genes back to their youthful position, effectively reversing the aging process.

Professor Hayashi. (Credit: University of Tsukuba)

The researchers came to this conclusion by comparing the function level of the mitochondria in fibroblast cell lines from children under 12 years of age to those of elderly people between 80 and 97. As expected, the older cells had reduced cellular respiration, but the older cells did not show more DNA damage than those from children. This discovery led the team to propose that the reduced cellular function is tied to epigenetic regulation, changes that alter the physical structure of DNA without affecting the DNA sequence itself, causing genes to be turned on or off. Unlike mutations that damage that sequence, as in the other, aforementioned theory of aging, epigenetic changes could possibly be reversed by genetically reprogramming cells to an embryonic stem cell-like state, effectively turning back the clock on aging.

For a broad comparison, imagine that a power surge hits your home's electrical system. If not properly wired, irreversible damage or even fire may result. However, imagine another home in which the same surge trips a switch in this home's circuit breaker box. Simply flipping that breaker back to the "on" position should make it operate as good as new. In essence, the Tsukuba team is proposing that our DNA may not become fried with age as previously thought, but rather simply requires someone to access its genetic breaker box to reverse aging.

To test the theory, the researchers found two genes associated with mitochondrial function and essentially experimented with turning them on or off. In doing so, they were able to create defects or restore cellular respiration. These two genes regulate glycine, an amino acid, production in mitochondria, and in one of the more promising findings, a 97-year-old cell line saw its cellular respiration restored after the addition of glycine for 10 days.

The researchers' findings were published this month in the journal Scientific Reports.

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. However, if the theory holds, glycine supplements could one day become a powerful tool for life extension.

Similar research from the Salk Institute has also recently looked at other ways to slow down or stop aging at a cellular level, while yet another team is looking into a new class of drugs called senolytics that could help slow aging.

Source: University of Tsukuba

ORIGINAL: Gizmag

ERIC MACK

MAY 27, 2015

Researchers nearly double the size of worker ants

MELANIE COUTURE AND DOMINIC OUELLETTE.  Florida carpenter ant workers run the gamut from dainty minors (far left) to hefty majors (far right).

Researchers have changed the size of a handful of Florida ants by chemically modifying their DNA, rather than by changing its encoded information. The work is the latest advance from a field known as epigenetics and may help explain how the insects—despite their high degree of genetic similarity—grow into the different varieties of workers needed in a colony.

This discovery “takes the field leaps and bounds forward,” says entomologist Andrew Suarez of the University of Illinois, Urbana-Champaign, who wasn’t connected to the study. “It’s providing a better understanding of how genes interact with the environment to generate diversity.”

Ant nests have division of labor down pat. The queen spends her time pumping out eggs, and the workers, which are genetically similar sisters, perform all the other jobs necessary to keep the colony thriving, such as tending the young, gathering food, and excavating tunnels. Workers in many ant species specialize even further, forming so-called subcastes that look different and have different roles. In Florida carpenter ants (Camponotus floridanus), for example, workers tend to fall into two groups.

• Minor workers, which can be less than 6 mm long, rear the young and forage for food. 
• Major workers, which can be almost twice as long, use their large jaws to protect the colony from predators.

A team from McGill University in Montreal, Canada, suspected that the mechanism involves DNA methylation: the addition of a chemical to DNA. Genome sequencing and other methods suggest that these physical differences don’t usually stem from genetic differences between individual ants. Instead, environmental factors help push workers to become majors or minors—specifically, the amount of food and coddling that young ants receive. But just how do these factors change the size of ants?

To test their idea, the researchers dosed Florida carpenter ant larvae with compounds that promote or curb methylation throughout the genome. Cells typically use DNA methylation to shut down the activity of specific genes, and past studies have suggested it alters growth in social insects. Researchers have found, for example, that reducing the amount of DNA methylation in bees, which are closely related to ants and have a similar social organization, spurs larvae to morph into queens. “We have provided a biological mechanism that can explain that difference” between major and minor workers, says Sebastian Alvarado, lead author on the paper, who is now at Stanford University in Palo Alto, California.

To test their idea, Alvarado and colleagues dosed Florida carpenter ant larvae with compounds that promote or curb methylation throughout the genome. The amount of methylation determined the workers’ adult size, the researchers report online today in Nature Communications. Increased methylation throughout the genome led to more minor workers, and reduced methylation resulted in more majors. “We have provided a biological mechanism that can explain that difference” between major and minor workers, Alvarado says.

Next, the researchers wanted to nail down which genes dictate the ants’ size. They measured the activity of several growth-controlling genes and found that the one whose activity increased the most in minor workers was the epidermal growth factor receptor (EGFR), suggesting it was responsible for their daintiness. Sure enough, the researchers found that blocking EGFR with a drug produces larger workers.

But the connection between methylation and worker size is more complicated than it first seemed, the team discovered after measuring the amount of methylation on EGFR. Increasing methylation throughout the genome led to reduced methylation of EGFR, resulting in increased EGFR activity and smaller workers. In contrast, reducing methylation overall caused increased methylation of EGFR and spawned heftier workers. The researchers hypothesize that the amount of food or care that an ant larva receives affects the overall amount of methylation in its genome. In turn, that level determines the activity of certain genes that control EGFR’s methylation, which helps set the larva’s growth pattern.

Major and minor workers don’t just look different—they also behave differently; minor workers are nurturers and providers, whereas major workers are head-breakers. “It would be interesting to see if a change in DNA methylation also changes their behavior,” Alvarado says. He and his colleagues are now trying to figure that out. 

*Correction, 11 March, 12:59 p.m.: This story has been updated to reflect the fact that some of the authors on the research team are at McGill University.

ORIGINAL: ScienceMag

By Mitch Leslie

11 March 2015