Posted on 01/09/2018 12:49:23 PM PST by Red Badger
The experimental drug J147 is something of a modern elixir of life; it's been shown to treat Alzheimer's disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk scientists have solved the puzzle of what, exactly, J147 does. In a paper published January 7, 2018, in the journal Aging Cell, they report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.
"This really glues together everything we know about J147 in terms of the link between aging and Alzheimer's," says Dave Schubert, head of Salk's Cellular Neurobiology Laboratory and the senior author on the new paper. "Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials."
Schubert's group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule found in the curry spice curcumin. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer's progression in mice. However, they didn't know how J147 worked at the molecular level.
In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP—the cell's energy currency—within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.
"We know that age is the single greatest contributing factor to Alzheimer's, so it is not surprising that we found a drug target that's also been implicated in aging," says Goldberg, the paper's first author.
Further experiments revealed that modulating activity of ATP synthase with J147 changes the levels of a number of other molecules—including levels of ATP itself—and leads to healthier, more stable mitochondria throughout aging and in disease.
"I was very surprised when we started doing experiments with how big of an effect we saw," says Schubert. "We can give this to old mice and it really elicits profound changes to make these mice look younger at a cellular and molecular level."
The results, the researchers say, are not only encouraging for moving the drug forward as an Alzheimer's treatment, but also suggest that J147 may be useful in other age-associated diseases as well.
"People have always thought that you need separate drugs for Alzheimer's, Parkinson's and stroke" says Schubert. "But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated."
The team is already performing additional studies on the molecules that are altered by J147's effect on the mitochondrial ATP synthase—which could themselves be new drug targets. J147 has completed the FDA-required toxicology testing in animals, and funds are being sought to initiate phase 1 clinical trials in humans.
Explore further: Experimental drug targeting Alzheimer's disease shows anti-aging effects
More information: The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell. DOI: 10.1111/acel.12715
Journal reference: Aging Cell
The calculation has already taken that into account. Freepers never like to read the article/watch the video....
Will we know it’s working when Minnie Mouse starts looking hot?
Or Daisy......................
“That (life expectancy differences) has already been accounted for in the calculation (for different rates of Alzheimer’s in high-curry consuming India vs. Pennsylvania)”
In that case, it is likely a very dramatic comparison, indicating a role for curcumin in preventing Alzheimer’s.
I don’t want to rain on the powerful support for curcumin found in that comparison (which I believe). Population studies are just so vulnerable to confounding factors. Vegetarianism is the norm in rural Hindu India. Genetic factors could be very distinct between those populations. Other components in curry (or chai tea) might be factors.
In my cursory analysis, I would think that Life expectancy would likely be the major confounding factor (as Alzheimer’s is so correlated to age), and other factors would be relatively much less influential.
The controlled study just published in Nature is much more definitive evidence.
Those are all good points.
The MD who runs NutritionFacts does a pretty good job of only using well designed studies. I don’t think that he tries to oversell the potential of turmeric in this video. Just that it looks promising.
True, but they are also have through the roof poverty, most of the country doesn't have proper sewage (i.e. feces in their water source) or routine vaccinations.
“The calculation has already taken that into account. Freepers never like to read the article/watch the video.”
Your link is to a video which cites some research from 2001.
Here is a link to the abstract cited in the video:
http://www.dementia-epidemiology.pitt.edu/IndoUS/IndoUS_ScientificReports/Chandra2001Incidence.pdf
Note the final paragraph of the abstract:
“There are other, possibly inter-related, reasons for the low incidence of AD in the Ballabgarh cohort. Low average life expectancy in India, with fewer persons living into age of risk, might reduce incidence, especially if there is selectively earlier mortality of those at increased risk. Low incidence rates may also suggest the presence of underlying protective factors, or the absence of underlying risk factors...
given the relatively short duration of follow-up in out study, the small number of incident cases, the wide confidence intervals, and our stated concerns about potential under-reporting of mild disability, we urge caution in the interpretation and generalization of our results.”
Like I said... the evidence from comparing people in India with Americans does not strongly support Turmeric and Curry being preventative of dementia.
However, it is certainly possible. I take Turmeric and Curcumin daily because these have many beneficial properties. I also consume a significant amount of coconut oil. I lost a close family member to dementia and am concerned that I will be at risk in my later years. I don’t know if these lifestyle choices will prevent or minimize my risk, but I do not think they will hurt.
Thanks for sharing.
“maybe that is their secret”
I think I’ll stick with Turmeric.
Even absent of a scientific study, I’m pretty confident that poor sanitation does nothing to prevent dementia.
So what am I supposed to do with all this J146?
Glad I take this already.
I’d like to see those young looking worms.
Although the lower dementia might be, as you say, because of lower lifespan, as dementia is related to aging.
I'm inclined to believe their diet i.e. low fat, less animal products, more minerals from spices, no processed garbage, chemical-laced foods, no soda, etc. only increases one's lifespan and general health.
I'm a firm believer that cardio exercise and healthy (i.e. real) food is a big deterrent to dementia and a host of other health ailments. But that's just me. :)
keeper
Trade it in.....................
Thanks for the referral.
I’m going to look into this, thanks.
You’re welcome. Their manufacturing process makes the curcumin much more bioavailable. I’m not fighting cancer, so I don’t need a 1000 mg capsule. It’s described at the link ...
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