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Life Extension Factor Klotho Enhances Cognition

aging brain genetics cognition

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#1 APBT

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Posted 09 May 2014 - 06:21 PM


Is this genetic information available on 23andme?

FULL TEXT:  http://www.cell.com/...1247(14)00287-3
 

Life Extension Factor Klotho Enhances Cognition
  Highlights
  • KLOTHO variant elevates klotho levels and is associated with enhanced human cognition
  • �Elevation of klotho in mice enhances normal cognition, independent of age
  • �Klotho elevation leads to greater synaptic GluN2B (NMDAR subunit) levels and plasticity
  • �GluN2B blockade abolishes klotho-mediated effects on NMDAR functions and cognition
Summary

Aging is the primary risk factor for cognitive decline, an emerging health threat to aging societies worldwide. Whether anti-aging factors such as klotho can counteract cognitive decline is unknown. We show that a lifespan-extending variant of the human KLOTHO gene, KL-VS, is associated with enhanced cognition in heterozygous carriers. Because this allele increased klotho levels in serum, we analyzed transgenic mice with systemic overexpression of klotho. They performed better than controls in multiple tests of learning and memory. Elevating klotho in mice also enhanced long-term potentiation, a form of synaptic plasticity, and enriched synaptic GluN2B, an N-methyl-D-aspartate receptor (NMDAR) subunit with key functions in learning and memory. Blockade of GluN2B abolished klotho-mediated effects. Surprisingly, klotho effects were evident also in young mice and did not correlate with age in humans, suggesting independence from the aging process. Augmenting klotho or its effects may enhance cognition and counteract cognitive deficits at different life stages.



#2 sthira

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Posted 09 May 2014 - 07:00 PM

Anti-Aging Hormone Could Make You Smarter
by Jon Hamilton

NPR - May 8, 2014

A hormone associated with longevity also appears to make people's brains work better....

http://www.npr.org/b...er?sc=17&f=1001

The finding in Cell Reports could someday lead to drugs that improve memory and learning, researchers say.

"We've discovered a way to potentially boost cognition," says Dena Dubal, one of the study's authors who does research on aging and the brain at the University of California, San Francisco. And that could mean "a very new way to treat diseases," ranging from Alzheimer's to schizophrenia, she says.

The hormone is named Klotho, after the Fate from Greek mythology who spins the thread of life. Scientists have known for more than a decade that people and animals tend to live longer if they have high levels of Klotho in their bodies.

And that led Dubal and researchers at the Gladstone Institutes to wonder whether a hormone that protects the body against aging might also protect the brain. So the team set out to see whether Klotho offered a way to "prevent the cognitive decline that comes with aging," Dubal says.

To find out, they studied more than 700 people between the ages of 52 and 85. About 1 in 5 of these people had a form of the Klotho gene that causes their bodies to produce high levels of the Klotho hormone.

The team expected to find that people with high levels of the hormone experienced less cognitive decline than people with lower levels. "In fact what we found was not consistent with our hypothesis," Dubal says. "We were completely surprised."

What they found was that the people with lots of Klotho experienced just as much cognitive decline as other people. Their brains weren't protected against aging at all. But their brains were different nonetheless, Dubal says.

"Those that carried the genetic variant that increased their Klotho levels showed better cognitive performance across the lifespan," Dubal says. At any given age, people with lots of Klotho scored higher on tests of learning and memory, language and attention, she says.

So instead of discovering a way to protect the brain from aging, the team had found a hormone that appears to make people smarter.

To learn more, the team began studying mice that had been genetically engineered to produce high levels of the mouse version of Klotho. And this time, the researchers got exactly the result they hoped for. "Elevating klotho made the mice smarter across all the cognitive tests that we put them through," Dubal says

A look at the brains of these mice suggested a reason. There was evidence that in areas involved in learning and memory, Klotho was causing a change that strengthened the connections between brain cells.

All this suggests that a drug able to raise levels of Klotho might be able to help people with Alzheimer's and other brain diseases, Dubal says, even if the drug didn't stop the disease itself. "Our goal and vision is that there will be a therapy that improves the lives of people that are suffering from diseases of the brain," Dubal says.

But any treatment based on manipulating Klotho levels in people remains years away, says Molly Wagster, who oversees research on cognitive change at the National Institute on Aging. The NIA and National Institute of Neurological Disorders and Stroke both helped fund the research.

"The beauty of this study is that the finding gives us another place to look, another path to take as we try to determine targets for the development of drugs," Wagster says. It also raises questions about whether Klotho levels may be influenced by diet, exercise or brain activity all of which have been shown to affect cognitive function in older people, she says.

There's a lot researchers still don't know about the Klotho, which was discovered in 1997. For example, it's not clear why carrying one copy of the gene associated with higher levels of the hormone improves cognitive function while carrying two copies seems to impair function.

But knowing that a naturally occurring hormone affects cognition in both mice and people should speed efforts to find treatments for diseases that cause impaired brain function, Wagster says. 

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#3 Razor444

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Posted 27 July 2014 - 10:37 PM

From 24 July, FYI:

 

 

Boston University School of Medicine researchers may have found a way to delay or even prevent Alzheimer's disease (AD). They discovered that pre-treatment of neurons with the anti-aging protein Klotho can prevent neuron death in the presence of the toxic amyloid protein and glutamate. These findings currently appear in the Journal of Biological Chemistry.

 

Alzheimer's disease is the most frequent age-related dementia affecting 5.4 million Americans including 13 percent of people age 65 and older and more than 40 percent of people over the age of 85. In AD the cognitive decline and dementia result from the death of nerve cells that are involved in learning and memory. The amyloid protein and the excess of the neurotransmitter, glutamate are partially responsible for the neuronal demise.

 

Nerve cells were grown in petri dishes and treated with or without Klotho for four hours. Amyloid or glutamate then were added to the dish for 24 hours. In the dishes where Klotho was added, a much higher percentage of neurons survived than in the dishes without Klotho.

 

"Finding a neuroprotective agent that will protect nerve cells from amyloid that accumulates as a function of age in the brain is novel and of major importance," explained corresponding author Carmela R. Abraham, PhD, professor of biochemistry and pharmacology at BUSM. "We now have evidence that if more Klotho is present in the brain, it will protect the neurons from the oxidative stress induced by amyloid and glutamate.

 

According to the researchers, Klotho is a large protein that cannot penetrate the blood brain barrier so it can't be administered by mouth or injection. However in a separate study the researchers have identified small molecules that can enter the brain and increase the levels of Klotho. "We believe that increasing Klotho levels with such compounds would improve the outcome for Alzheimer's patients, and if started early enough would prevent further deterioration. This potential treatment has implications for other neurodegenerative diseases such as Parkinson's, Huntington's, ALS and brain trauma, as well," added Abraham.

 

 



#4 eon

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Posted 11 February 2015 - 11:55 AM

I was wondering how scientists determine how much Klotho the rats have or are they artificially increasing the rat's Klotho levels, and how so? Obviously I'm seeking something to increase my Klotho levels but none of the articles I've read so far ever mentioned it. It's probably still too early for anyone to figure it all out.

 

Protein linked to longevity and enhanced cognition protects against Alzheimer's symptoms

 

http://medicalxpress...-alzheimer.html

 

"Scientists from the Gladstone Institutes and the University of California, San Francisco report in the Journal of Neuroscience that raising levels of the life-extending protein klotho can protect against learning and memory deficits in a mouse model of Alzheimer's disease. Remarkably, this boost in cognition occurred despite the accumulation of Alzheimer-related toxins in the brain, such as amyloid-beta and tau."

 

"Klotho decreases naturally with aging, which also leads to a decline in cognitive ability. An earlier study from these researchers revealed that having a genetic variant that increases klotho levels is associated with better cognition in normal, healthy individuals, and experimentally elevating klotho in mice enhances learning and memory. However, klotho's influence in the face of aging-related cognitive disorders like Alzheimer's disease was unclear."

 

They never mentioned how they were experimentally elevating klotho levels in mice and if this is possible with humans as well.

 

"Klotho's benefits may be due to its effect on a certain type of neurotransmitter receptor in the brain, called NMDA, that is crucially involved in learning and memory."

 

So do we look for drugs that affect NMDA? How about some Magnesium?

 

"The next step will be to identify and test drugs that can elevate klotho or mimic its effects on the brain," says senior author Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and the Joseph B. Martin Distinguished Professor of Neuroscience at UCSF. "We are encouraged in this regard by the strong similarities we found between klotho's effects in humans and mice in our earlier study. We think this provides good support for pursuing klotho as a potential drug target to treat cognitive disorders in humans, including Alzheimer's disease."

 

I still wonder what it was they were using to elevate Klotho in mice, experimentally. They could start looking into making something out of it.

 


Edited by eon, 11 February 2015 - 11:56 AM.


#5 Razor444

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Posted 04 April 2015 - 01:31 PM

From reddit: Science AMA Series: I'm Dena Dubal, a neurologist and neuroscientist. My group discovered that an anti-aging hormone could make you "smarter". My hope is that we can use this to "boost the brain" and treat diseases. AMA!

 

 

Hi reddit!

My lab is focused on shoring up the brain against the insults of aging. We know that many people, when their post-mortem brains are examined, turn out to have extensive Alzheimer's pathology, even though they were cognitively normal when they were alive. Something must have protected them. KLOTHO is a longevity hormone that circulates in our body and acts to make tighter, better connections at the synapse, and may partly explain this mystery. It probably optimizes a lot of other brain functions, too.

We’re taking a completely new approach to dementia therapy, which, until now, has focused on removing the build up of toxic proteins in the brain.

I'll be back at 2 pm EDT to answer your questions, ask me anything!

My lab at UCSF: http://www.duballab.org/wp/

Me on Twitter: @DenaDubal

A recently published paper about our work: http://onlinelibrary...2/acn3.161/epdf

Recent UCSF write-up about KLOTHO: https://www.ucsf.edu...ty-gene-variant

NIH release about KLOTHO: http://www.nih.gov/n...14/ninds-09.htm

NPR article: http://www.npr.org/b...ake-you-smarter

Economist article: http://www.economist...y-has-just-been

EDIT: Schedule typo, I'll be back at 2pm EDT, 11 am PST

EDIT: Hi everyone! Thanks for joining me today. Excited to start answering questions!

EDIT: So many fascinating questions - thanks for submitting them and engaging in this terrific forum. I wish I could have gotten to them all. Stay tuned for more on klotho and brain resilience. . . Signing off.

 


Edited by Razor444, 04 April 2015 - 01:32 PM.


#6 YOLF

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Posted 06 April 2015 - 08:44 PM

Ok, so we can boost kotho with tocotrienols, D, and a few other things and there are heaps of benefits from having higher klotho levels and taking supplements that boost klotho. There are also things like tocopherols and synthetic E that lowers klotho.

 

My question is, would supplementing these things and then suddenly removing them, adding things that lower klotho for a week or two create a sensolytic effect? Tocopherols are cheap and readily available everywhere, just stay out of the sun to decrease D. 

 

Is there any kind of inexpensive testing that can be done for klotho levels?

 

Being that diet and supplementation can do so much for klotho levels it might be a blessing in disguise for those of us who don't have it.

 

I'll be posting another topic further expanding on this. 



#7 normalizing

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Posted 15 February 2017 - 03:19 AM

hi i just read this on klotho; http://www.medicalne...ases/315826.php

 

so, im curious since i cant find any paper stating you can increase it by supplementation, i have to ask can one do that and which supplements can do this??



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#8 HaplogroupW

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Posted 14 April 2017 - 08:45 AM

 

Is this genetic information available on 23andme?

 

yes, see:

http://www.snpedia.c...x.php/Rs9536314


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