Posts Tagged ‘autophagy’

by CHRISTIAN COTRONEO

If the startling results of a recent Austrian study are any indication, we should all get better acquainted with ashitaba.

In fact, we might even want to make a little room for this ancient Japanese plant beside the basil and lavender in the windowsill.

Ashitaba may have a bright future in Western households because the so-called “Tomorrow’s Leaf” promises just that: A future.

In a paper published this month in the journal Nature, researchers at the University of Graz, suggest a key component of the plant — called 4,4′-dimethoxychalcone, or DMC — may act as an anti-aging mechanism.

In experiments, the substance was found to prolong the lives of worms and fruit flies by as much as 20 percent.

Keeping the cellular process tidy
Researchers suggest DMC acts as a kind of “cellular garbage collector.” It basically speeds along the natural process by which frail and damaged cells are shed to be replaced by shiny new ones.

Normally, the crusty old cells are removed regularly through a process called autophagy. But as we age, the body’s trash collector starts missing appointments, allowing the damaged cells to accumulate, opening the door for a wide range of diseases and disorders.

In the experiments, DMC kept the process whirring along.

So what exactly is this humble hero — and more importantly, why haven’t we carpeted the planet with it yet?

Well, it’s not much to look at, and its leaves are said to be rather bitter — but that likely just gives adds more cred for its centuries-long use as a traditional medicine.

Let’s face it, practitioners of traditional medicine were probably the first to offer the cheerful slogan, “It tastes awful and it works.”

And those ancient chemists stood by the myriad benefits of Angelica keiskei — the plant’s botanical name — touting its powers of increasing breast milk flow, easing blood pressure and even calming the savage ulcer.

Samurai, too, were notorious nibblers— not so much for the plant’s breast milk-boosting ways, but rather its reputation for adding years to one’s life.

But does it really work? Or does it get a pass from traditional medicine because it tastes awful?

Keep in mind that Austrian researchers developed an intensive process to isolate the DMC, administering concentrated dosages to subjects. You’re not likely to be overwhelm your anti-aging genes by chewing on a bale of ashitaba, or making it into a nice tea.

Also, although this was the first time DMC was tested on living animals, there’s a wide chasm between worms and human beings. Countless promising experiments involving animals have crashed hard against the very different reality of human biology.

“The experiments indicate that the effects of DMC might be transferable to humans, although we have to be cautious and wait for real clinical trials,” Frank Madeo, lead author of the study, tells Medical News Today.

Human testing, he adds, will follow, only after researchers see how DMC fares at torquing the hearts of mice.

Of course, that doesn’t mean you can’t get a headstart on what could well become the ultimate opiate for the age-obsessed masses — and grow your own little ashitaba garden.

“Angelicas [another name for the plant] like to be cold stratified,” San Francisco Botanical Garden curator Don Mahoney tells Modern Farmer.

That means keeping the seeds outside at night, preferably in 30-degree temperatures, to help them germinate. As an alternative, Mahoney suggests, a couple of weeks in the fridge could kickstart the process.

“Nearly all of my last batch of seeds germinated,” he explains.

From there, it’s all in the hands of quality soil, while you gradually increase the pot size until the seedling are ready for the ground.

Ashitaba is partial to cool, damp conditions. So in the summer, it might seem like you messed up yet another gardening gambit. But then, when things cool down, “Tomorrow’s Leaf” rises mightily to the occasion.

The plants generally grow to around four feet high. Not only that, but they have a remarkable knack for rejuvenating themselves — a leaf cut off in the morning will start growing back the next day.

As far as looks go, ashitaba, which is a relative of the carrot, isn’t going to make your begonias blush. But its leaves, stems and yellow sap still course with nutrients. Even if the age-torquing upside doesn’t work out, it still packs promise for ulcers and breast milk and even blood pressure.

At the very least, all that promise of extending life will be a nice conversation piece — even if all it ever ends up enlivening is your salad.

And remember: Even the samurai died of old age at some point.

https://www.mnn.com/your-home/organic-farming-gardening/stories/ashitaba-plant-antiaging-properties-how-to-grow

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Brown University researchers studying the biology of aging have demonstrated a new strategy for stimulating autophagy, the process by which cells rebuild themselves by recycling their own worn-out parts.

In a study published in the journal Cell Reports, the researchers show that the approach increased the lifespans of worms and flies, and experiments in human cells hint that the strategy could be useful in future treatments for Alzheimer’s disease, ALS and other age-related neurodegenerative conditions.

“Autophagy dysfunction is present across a range of age-related diseases including neurodegeneration,” said Louis Lapierre, an assistant professor of molecular biology, cell biology and biochemistry at Brown who led the work. “We and others think that by learning how to influence this process pharmacologically, we might be able to affect the progression of these diseases. What we’ve shown here is a new and conserved entry point for stimulating autophagy.”

Autophagy has become a hot topic in recent years, earning its discoverer the Nobel Prize in Physiology and Medicine in 2016. The process involves the rounding up of misfolded proteins and obsolete organelles within a cell into vesicles called autophagosomes. The autophagosomes then fuse with a lysosome, an enzyme-containing organelle that breaks down those cellular macromolecules and converts it into components the cell can re-use.

Lapierre and his colleagues wanted to see if they could increase autophagy by manipulating a transcription factor (a protein that turns gene expression on and off) that regulates autophagic activity. In order for the transcription factor to switch autophagic activity on, it needs to be localized in the nucleus of a cell. So Lapierre and his team screened for genes that enhance the level of the autophagy transcription factor, known as TFEB, within nuclei.

Using the nematode C. elegans, the screen found that reducing the expression of a protein called XPO1, which transports proteins out of the nucleus, leads to nuclear accumulation of the nematode version of TFEB. That accumulation was associated with an increase in markers of autophagy, including increased autophagosome, autolysosomes as well as increased lysosome biogenesis. There was also a marked increase in lifespan among the treated nematodes of between about 15 and 45 percent.

“What we showed was that by blocking the escape of this transcription factor from the nucleus, we could not only influence autophagy but we could get an increase in lifespan as well,” Lapierre said.

The next step was to see if there were drugs that could mimic the effect of the gene inhibition used in the screening experiment. The researchers found that selective inhibitors of nuclear export (SINE), originally developed to inhibit XPO1 to treat cancers, had a similar effect — increasing markers of autophagy and significantly increasing lifespan in nematodes.

The researchers then tested SINE on a genetically modified fruit fly that serves as a model organism for the neurodegenerative disease ALS. Those experiments showed a small but significant increase in the lifespans of the treated flies. “Our data suggests that these compounds can alleviate some of the neurodegeneration in these flies,” Lapierre said.

As a final step, the researchers set out to see if XPO1 inhibition had similar effects on autophagy in human cells as it had in the nematodes. After treating a culture of human HeLa cells with SINE, the researchers found that, indeed, TFEB concentrations in nuclei increased, as did markers of autophagic activity and lysosomal biogenesis.

“Our study tells us that the regulation of the intracellular partitioning of TFEB is conserved from nematodes to humans and that SINE could stimulate autophagy in humans,” Lapierre said. “SINE have been recently shown in clinical trials for cancer to be tolerated, so the potential for using SINE to treat other age-related diseases is there.”

Future research, Lapierre said, will focus on testing these drugs in more clinically relevant models of neurodegenerative diseases. But this initial research is a proof of concept for this strategy as a means to increase autophagy and potentially treat age-related diseases.

Lapierre is a faculty member in the newly approved Center on the Biology of Aging within the Brown Institute for Translational Science. This center, led by Professor of Biology John Sedivy, studies the biological mechanisms of aging. The center’s mission is to expand biomedical research and education programs in the emerging discipline of biogerontology, and to bring forth scientific discoveries related to aging and associated disorders.