Anti-aging therapy is one step closer after successful primate trial

You already lost 5 years because of your stroke. Ask your doctor how you are going to make up those lost years.
Are ANY of these earlier researches put into practice at your hospital? 

This Fruit Reverses Brain Ageing - strawberries March 2018 

One Serving Of These Slows Brain Aging By 11 Years - Leafy green vegetables December 2017

 Be careful if you are on warfarin, don't do this on your own.  DEMAND your doctor get you a diet protocol because you can't do this dangerous food on your own. 

Would you rather try young blood?

OR;

  Cannabis Reverses Aging Processes in the Brain

I'll be doing this one, Michigan has approved recreational marijuana.

Eat This Once A Week To Reduce Brain Aging - seafood  November 2017 

German Study Finds Marijuana May Reverse Brain Aging, Memory Loss  May 2017

The latest here:

 

Anti-aging therapy is one step closer after successful primate trial

By Bronwyn Thompson

July 04, 2023

Boosting klotho expression after it naturally depletes could have vast anti-aging health benefits

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More than 30 years after it was identified as a key ‘longevity gene,’ the protein klotho has been used to boost the cognitive function of aging rhesus macaques, paving the way for human trials.

Following on from recent mice models, an international team of scientists found that the working memory and task-completion abilities of 18 rhesus macaques (Macaca mulatta), aged an average of 22 years (the human-equivalent of around 65), was boosted when injected with the klotho protein.

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The researchers include scientists from the University of California, San Francisco, Weill Institute for Neurosciences, who have focused studies on klotho and regenerative cognitive function for more than half a decade.

In the study, the monkeys had to repeatedly navigate easy and difficult mazes to find a treat, in order to see how well they remembered the most direct path. The animals repeated the tasks four hours later. after being dosed with klotho, raising the protein levels to that of juveniles. While they only showed a 6% average improvement for the easy mazes, they fared about 20% better on the harder task. The memory boost was shown to last at least two weeks.

Interestingly, the dosage was relatively much lower than in mice trials.

The transmembrane protein family klotho, which as three subfamilies, including the most often referenced alpha-klotho, was only identified in 1997 and its function is still not completely understood. However, it does play a key role in aging, regulating many of the pathways such as phosphate levels and insulin signaling.

The protein, named after the Greek goddess Clotho who spun the thread of human life, is naturally produced in the kidneys and depletes with age. Its deficiency is a factor in arterial stiffening, hypertension and vascular degeneration, among many other age-related health conditions.

Previously, studies have shown how klotho expression has boosted cognitive function in mice models, from how intermittent fasting influenced its levels to how plasma transfusions from younger to older animals resulted in muscle regeneration.

One of the current study’s co-authors, Dena Dubal compares the cognitive tests to real-world experiences like needing to remember where you left your car in a parking lot, or recalling a string of numbers, two skills that decline as you age.

Dubal, now a physician-researcher at the University of California San Francisco’s Weill Institute for Neurosciences, has been studying the life-extending potential of klotho for years.

“For humans, the end game really is: how can we increase our ‘healthspan?’” Dubal said in 2018. “And that may go hand in hand with an increase in lifespan, because the things that help us to live longer are also the things that help us to live better.”

While there’s still much unknown about the mechanisms involved in klotho’s restorative abilities, Dubal said this current research provides “a very strong reason to jump into human clinical trials now.”

The research was published in the journal Nature Aging.

Sources: Nature, Weill Institute for Neurosciences, Medical Xpress

One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?

You already lost 5 years because of your stroke. Ask your doctor how you are going to make up those lost years.
Are ANY of these earlier researches put into practice at your hospital? 

This Fruit Reverses Brain Ageing - strawberries March 2018 

One Serving Of These Slows Brain Aging By 11 Years - Leafy green vegetables December 2017

 Be careful if you are on warfarin, don't do this on your own.  DEMAND your doctor get you a diet protocol because you can't do this dangerous food on your own. 

Would you rather try young blood?

OR;

  Cannabis Reverses Aging Processes in the Brain

I'll be doing this one, Michigan has approved recreational marijuana.

Eat This Once A Week To Reduce Brain Aging - seafood  November 2017 

German Study Finds Marijuana May Reverse Brain Aging, Memory Loss  May 2017

The latest here:

One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?

By Carl Zimmer

• April 2, 2019

Leer en español

In 2011, Dr. Dena Dubal was hired by the University of California, San Francisco, as an assistant professor of neurology. She set up a new lab with one chief goal: to understand a mysterious hormone called Klotho.

Dr. Dubal wondered if it might be the key to finding effective treatments for dementia and other disorders of the aging brain. At the time, scientists only knew enough about Klotho to be fascinated by it.

Mice bred to make extra Klotho lived 30 percent longer, for instance. But scientists also had found Klotho in the brain, and so Dr. Dubal launched experiments to see whether it had any effect on how mice learn and remember.

The results were startling. In one study, she and her colleagues found that extra Klotho protects mice with symptoms of Alzheimer’s disease from cognitive decline. “Their thinking, in every way that we could measure them, was preserved,” said Dr. Dubal.

She and her colleagues also bred healthy mice to make extra Klotho. They did better than their fellow rodents on learning mazes and other cognitive tests.

Klotho didn’t just protect their brains, the researchers concluded — it enhanced them. Experiments on more mice turned up similar results.

“I just couldn’t believe it — was it true, or was it just a false positive?” Dr. Dubal recalled. “But here it is. It enhances cognition even in a young mouse. It makes them smarter.”

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Five years have passed since Dr. Dubal and her colleagues began publishing these extraordinary results. Other researchers have discovered tantalizing findings of their own, suggesting that Klotho may protect against other neurological disorders, including multiple sclerosis and Parkinson’s disease.

Now Dr. Dubal and other researchers are trying to build treatments based on these results. Either by injecting Klotho into the body or by stimulating the brain to make more of the hormone, they hope to treat diseases like Alzheimer’s.

The researchers developing these treatments readily acknowledge that they may fail. And other Klotho experts think there’s a huge amount of work left to do first to figure out how Klotho affects the brain.

“You’ve got all of this amazing stuff showing a really major impact, but we can’t really explain why,” said Gwendalyn D. King, a neuroscientist at the University of Alabama at Birmingham. “That’s where we’re stuck.”

But what happens if scientists get unstuck? What if a drug that enhances cognition really were possible?

Eric Juengst, the director of the University of North Carolina Center for Bioethics, has been thinking about these questions for two decades — back when such drugs were little more than thought experiments.

We tend to think of drugs that enhance performance — say, sports doping — as bad. Drugs that cure or prevent diseases are good. “The scientific community and the public all draw that line,” said Dr. Juengst.

When it comes to Klotho, there may be no such line. In theory, such a drug might offer both a way to prevent diseases of the brain and to enhance it.

Recent research is giving these questions a sudden urgency, according to Dr. Juengst.

“It’s exciting for someone who’s been doing armchair work on this for a long time to see it happening in the real world,” he said. “But it also makes it all the more pressing that this conversation get started in earnest.”

One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?

Ask your doctor and stroke hospital to followup and see how close to regular use this is. Survivors should be able to benefit. 

One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?

By Carl Zimmer

• April 2, 2019

In 2011, Dr. Dena Dubal was hired by the University of California, San Francisco, as an assistant professor of neurology. She set up a new lab with one chief goal: to understand a mysterious hormone called Klotho.

Dr. Dubal wondered if it might be the key to finding effective treatments for dementia and other disorders of the aging brain. At the time, scientists only knew enough about Klotho to be fascinated by it.

Mice bred to make extra Klotho lived 30 percent longer, for instance. But scientists also had found Klotho in the brain, and so Dr. Dubal launched experiments to see whether it had any effect on how mice learn and remember.

The results were startling. In one study, she and her colleagues found that extra Klotho protects mice with symptoms of Alzheimer’s disease from cognitive decline. “Their thinking, in every way that we could measure them, was preserved,” said Dr. Dubal.

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She and her colleagues also bred healthy mice to make extra Klotho. They did better than their fellow rodents on learning mazes and other cognitive tests.

Klotho didn’t just protect their brains, the researchers concluded — it enhanced them. Experiments on more mice turned up similar results.

“I just couldn’t believe it — was it true, or was it just a false positive?” Dr. Dubal recalled. “But here it is. It enhances of cognition even in a young mouse. It makes them smarter.”

[Like the Science Times page on Facebook. | Sign up for the Science Times newsletter.]

Five years have passed since Dr. Dubal and her colleagues began publishing these extraordinary results. Other researchers have discovered tantalizing findings of their own, suggesting that Klotho may protect against other neurological disorders, including multiple sclerosis and Parkinson’s disease.

Now Dr. Dubal and other researchers are trying to build treatments based on these results. Either by injecting Klotho into the body or by stimulating the brain to make more of the hormone, they hope to treat diseases like Alzheimer’s.

The researchers developing these treatments readily acknowledge that they may fail. And other Klotho experts think there’s a huge amount of work left to do first to figure out how Klotho affects the brain.

“You’ve got all of this amazing stuff showing a really major impact, but we can’t really explain why,” said Gwendalyn D. King, a neuroscientist at the University of Alabama at Birmingham. “That’s where we’re stuck.”

But what happens if scientists get unstuck? What if a drug that enhances cognition really were possible?

Eric Juengst, the director of the University of North Carolina Center for Bioethics, has been thinking about these questions for two decades — back when such drugs were little more than thought experiments.

We tend to think of drugs that enhance performance — say, sports doping — as bad. Drugs that cure or prevent diseases are good. “The scientific community and the public all draw that line,” said Dr. Juengst.

When it comes to Klotho, there may be no such line. In theory, such a drug might offer both a way to prevent diseases of the brain and to enhance it.

Recent research is giving these questions a sudden urgency, according to Dr. Juengst.

“It’s exciting for someone who’s been doing armchair work on this for a long time to see it happening in the real world,” he said. “But it also makes it all the more pressing that this conversation get started in earnest.”

The rest is behind the NYTimes paywall unless it is one of the free articles you can get. 

Longevity hormone boosts memory and protects against brain aging in mice - Klotho

You already lost 5 years because of your stroke. Ask your doctor how you are going to make up those lost years.
Are ANY of these earlier researches put into practice at your hospital? 

This Fruit Reverses Brain Ageing - strawberries March 2018 

One Serving Of These Slows Brain Aging By 11 Years - Leafy green vegetables December 2017

 Be careful if you are on warfarin, don't do this on your own.  DEMAND your doctor get you a diet protocol because you can't do this dangerous food on your own. 

Would you rather try young blood?

OR;

  Cannabis Reverses Aging Processes in the Brain

I'll be doing this one, Michigan has approved recreational marijuana.

Eat This Once A Week To Reduce Brain Aging - seafood  November 2017 

German Study Finds Marijuana May Reverse Brain Aging, Memory Loss  May 2017

The latest here but in mice so no use to you.

 Longevity hormone boosts memory and protects against brain aging in mice - Klotho

FULL STORY

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This illustration shows how klotho treatment in mice rapidly improved learning and memory of a hidden platform in a water maze.

Credit: Leon et al.

In a study that augurs well for the therapeutic potential of klotho -- a life-extending protein hormone that a minority of people naturally produce at high levels -- scientists at UC San Francisco have found that administering a fragment of the klotho protein to young, aging or impaired mice rapidly improves their cognitive and physical performance.

While previous studies had revealed associations between elevated klotho levels and better cognition, that research had been done with mice genetically engineered to continuously produce high klotho levels and in people carrying genetic variants that caused them to have high klotho levels throughout life. As a result, it was still unclear whether klotho could be administered like a drug to rapidly enhance cognitive functioning in mice or people with normal or low levels of the hormone.
"The burning question in the field was, 'Does klotho have therapeutic potential?'" said Dena Dubal, MD, PhD, associate professor of neurology, David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease at UCSF, and senior author of the new paper. "We now know that, yes, it does."
The study, published online Aug. 8, 2017, in Cell Reports, showed clear evidence of improved cognition across a range of domains -- including spatial learning and memory, as well as working memory. But it remains unexplained how the piece of the klotho hormone that the researchers injected into the bodies of the mice caused these effects, since there is no evidence that klotho is able to enter the brain from the bloodstream.
"It makes us wonder about the connection between the body and the brain," said Dubal, a member of the UCSF Weill Institute for Neurosciences. "What we saw with acute klotho administration may be similar to what happens with exercise, which also improves cognition and brain health, although we don't know how."
The beneficial effects that Dubal and her team saw in young mice occurred within hours, and they far outlasted the time that klotho remained active in the body. "It suggests to me that there is a long-lasting effect of even a single treatment, and it probably has to do with the remodeling of synapses, the sites where communication among nerve cells takes place," she said.
The team also tested aged mice that, at 18 months old, are at about the same stage in the mouse lifespan as a 65-year-old human, and found that a single injection of klotho was enough to significantly improve their ability to navigate and to learn new tasks.
The researchers then looked at mice that were engineered to produce a human protein called alpha-synuclein, which is a hallmark of Parkinson's disease and contributes to Alzheimer's disease. Alpha-synuclein is believed to contribute to the movement disturbances seen in Parkinson's. Giving klotho to these mice improved their motor function. The klotho-treated mice also learned better and were more willing than untreated mice to explore new territory, even though their brains remained loaded with toxic proteins. This suggests that the treatment might somehow make diseased brains more resilient.
"There's stronger and stronger evidence that the body works in a very integrated way, and that systemic effects profoundly affect the resilience of our brain," Dubal said.
Klotho, which is naturally produced in both the kidney and the brain, is a complex hormone that affects many different systems in the body, and it has several forms. Once produced, it lodges itself in cell membranes, then enzymes cleave off a portion that circulates in the blood and the cerebrospinal fluid that bathes the brain and spinal cord.
The klotho fragment that Dubal's team injected into mice is similar to the cleaved piece of the hormone that naturally circulates in the blood. But since klotho does not cross the so-called blood-brain barrier, which blocks the entry of some substances from the general circulation into the brain, researchers do not know exactly how it alters brain function.
Members of Dubal's lab had previously shown that mice carrying genetic modifications that exposed them to high klotho levels from birth had greater numbers of a synaptic protein called the GluN2B subunit, which is implicated in long-term potentiation, a strengthening of synapses that is critical to learning and memory. The researchers leading the current study expected to find a greater abundance of GluN2B in the klotho-treated mice, but they did not.
Instead, "after many months of repeating experiments and analyzing the data, we slowly realized that klotho treatment was increasing activation of the subunits that were already there," said Julio Leon, PhD, first author and a postdoctoral fellow in Dubal's lab.
To confirm these findings, the researchers selectively blocked the GluN2B subunits to see if they could still be activated by klotho, and found that they could not. Then they performed an unbiased analysis of about 4,000 proteins to see which ones changed together in the brains of the klotho-treated mice, an analysis that pointed to glutamate receptor signaling, which involves GluN2B, as the main pathway affected by klotho treatment.
Dubal said the new findings, along with others like the experiments involving exercise or those in which older mice have been rejuvenated with blood from younger mice, are helping to illuminate the dimly understood connections between the body and the brain.
"All of this work is going to teach us something really important about how the body transmits resilience to the brain," she said. "That's where this is taking us."

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Story Source:
Materials provided by University of California - San Francisco. Original written by Laura Kurtzman. Note: Content may be edited for style and length.

---

Journal Reference:

1. Julio Leon, Arturo J. Moreno, Bayardo I. Garay, Robert J. Chalkley, Alma L. Burlingame, Dan Wang, Dena B. Dubal. Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice. Cell Reports, 2017; 20 (6): 1360 DOI: 10.1016/j.celrep.2017.07.024

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University of California - San Francisco. "Longevity hormone boosts memory and protects against brain aging in mice: Mice treated with klotho do better on tests of memory and motor skills." ScienceDaily. ScienceDaily, 8 August 2017. .

 

 

Could a protein called klotho block dementia and aging?

I don't know. WHOM is going to followup? 

Could a protein called klotho block dementia and aging?

Neurologist and neuroscientist Dena Dubal, MD, Ph.D., is taking an innovative approach to battling neurodegenerative diseases like Alzheimer's disease and dementia. Rather than trying to understand the specific mechanisms that cause each disease, she took a step back and asked, "What do all these conditions have in common?"

The answer: old age.
Over time, something happens to our cells and organs, and in the past three decades scientists have begun to unravel exactly what that something is – and the cellular mechanisms our bodies use to fight it.
Dubal, an associate professor of neurology at UC San Francisco, thinks we can use the science of aging to help stave off these neurodegenerative diseases.
"Aging is the biggest risk factor for cognitive problems, and cognitive problems are one of the biggest biomedical challenges that we face," she said. "Why don't we just block aging?"
Blocking aging is easier said than done, but Dubal jumped head first into the problem by studying a protein called klotho.
Klotho was named after the Greek fate Clotho, a mythological figure who spun the thread of life and had say over when gods and mortals lived and died. The Japanese researchers who named the protein found that the amount of klotho produced by mice could affect how long the rodents lived. Other researchers later discovered that humans who naturally have more klotho tend to live longer.
Living longer is one thing, but Dubal, a member of the UCSF Weill Institute for Neurosciences, wanted to know if klotho could help our brains stay healthier and more resilient to cognitive problems. Could klotho levels predict how quickly subjects solved a variety of puzzles that test cognition? In both humans and mice, she found the same result: more klotho meant better cognitive function.
To bring this boost in brain health to everyone, and not just the 20 percent of people who happen to have naturally high klotho, Dubal is testing the protein's potential as a therapeutic. The protein can exist in two forms: the first is anchored to the cell membranes of your organs, mostly your brain and kidneys; and the second occurs when the protein is cut loose from its anchor and freed to float around the bloodstream. Dubal found that by simply injecting this floating form into mice, she could re-create the cognitive boost she found by genetically increasing klotho.
"We found that those mice that had been treated, within four hours had better brain function," she said. This worked in young mice, old mice, and mice that had a condition similar to Alzheimer's.
Next, Dubal's lab will try to understand how klotho acts on the brain without crossing the blood-brain barrier. And ultimately, could klotho become a therapy for humans to improve brain health and protect against aging and disease?
"For humans, the end game really is: how can we increase our 'healthspan?'" said Dubal. "And that may go hand in hand with an increase in life span, because the things that help us to live longer are also the things that help us to live better."
Hear the full story on Carry the One Radio:

Explore further: Hormone shows promise as cognition enhancer

Provided by: University of California, San Francisco

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

Ask your doctor for a definitive dementia prevention protocol. Not just the unusable generalities  from Mayo clinic, or the generic crap from Harvard. 

My complete list here: Don't listen to me, your doctor obviously knows more than I do. Have him/her prove that knowledge or fire them.
Dementia prevention 19 ways

The latest here:

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

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.
To test klotho's protective capacity, the scientists created a mouse model of Alzheimer's disease that produced higher levels of this protein throughout the body. Ordinarily, Alzheimer's-model mice have cognitive deficits, abnormal brain activity, and premature death, but raising klotho levels ameliorated these problems. The cognition-enhancing effects of the protein were powerful enough to counteract the effects of Alzheimer-related toxins, whose levels were unchanged.
"It's remarkable that we can improve cognition in a diseased brain despite the fact that it's riddled with toxins," says lead author Dena Dubal, MD, PhD, an assistant professor of neurology and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease at UCSF. "In addition to making healthy mice smarter, we can make the brain resistant to Alzheimer-related toxicity. Without having to target the complex disease itself, we can provide greater resilience and boost brain functions."
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. While Alzheimer's impairs NMDA receptors, the mice with klotho elevation maintained normal receptor levels. In addition, these mice had more GluN2B—a subunit of NMDA—than control animals. This increase may have contributed to the protective effects of klotho, counteracting the detrimental impact of Alzheimer-related toxicity on the brain.
"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."

 

 

Longevity Gene Linked to Better Brain Skills

Is your doctor going to be testing you for this post-stroke to determine your cognitive needs?

And look at that, it comes from that font of socialism, the government program NIH.

Longevity Gene Linked to Better Brain Skills

People with a variant form of a lifespan-related gene tend not only to live longer but to have better cognitive skills than those who lack the variant, a new study reports. Experiments done in mice might help explain why. The findings could lead to new approaches for improving thinking skills at various life stages.

The gene KLOTHO is named for a Greek mythological goddess of fate. Previous studies found that increased levels of the klotho protein can extend lifespan, whereas disruption of klotho can speed up aging. It’s been unclear, however, whether klotho might also have an effect on cognitive function, which typically declines with age.
To examine the potential link between klotho and cognition, Dr. Dena Dubal of the University of California, San Francisco, and her colleagues focused on a KLOTHO variant called KL-VS. Earlier studies had found that people with one copy of this variant tend to live longer and have a reduced risk for stroke. In contrast, having 2 copies of the KL-VS variant (a rare occurrence) had opposite effects on lifespan and stroke risk.
The researchers analyzed the relationship between KL-VS and cognition in more than 700 people, ages 52 to 85, who had no signs of dementia and were all participating in clinical studies. The research was supported in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Aging (NIA). The study appeared online in Cell Reports on May 7, 2014.
The participants were given a variety of cognitive tests, including measures of learning, memory, and attention. The 26% of participants who carried just one copy of the KL-VS variant performed better on the tests than those who had no copies, at all ages. Because people with the KL-VS variant also had elevated blood levels of klotho, the researchers concluded that the variant might enhance cognition by boosting klotho activity or levels.
The researchers next examined how the klotho protein affects learning and memory in mice. Mice genetically engineered to overproduce klotho lived longer and had higher levels of klotho in the brain’s hippocampus, an area that controls some types of learning and memory. The klotho-enhanced mice performed better on several learning and memory tests, regardless of age. In one test, the mice remembered the location of a hidden target in a maze better, which allowed them to find it twice as fast as control mice.
Brain tissue analysis of the klotho-enhanced mice showed that their synapses had more of a receptor subunit called GluN2B than control mice. The presence of GluN2B at synapses has previously been associated with changes in synaptic strength and learning and memory. When klotho mice were treated with a drug that blocked GluN2B-containing receptors, their ability to perform on learning and memory tests was reduced. The results suggest that increasing the presence of GluN2B-containing receptors may be one way that klotho could enhance cognitive skills.
“This could be a major step toward helping millions around the world who are suffering from Alzheimer’s disease and other dementias,” says Dubal. “If we could boost the brain’s ability to function, we may be able to counter dementias.” The researchers caution, however, that additional research is needed to better understand the effects of klotho.