Scientists May Have Found How to Stop Brain Ageing

**kellyhound** · #1 ● 09-02-2025, 10:15 AM

Aging is particularly harsh on the hippocampus, the brain region responsible for learning and memory.

Now, researchers at UC San Francisco have identified a protein that’s at the center of this decline.

They looked at how the genes and proteins in the hippocampus changed over time in mice and found just one protein that differed between old and young animals. It’s called FTL1. Old mice had more FTL1, as well as fewer connections between brain cells in the hippocampus and diminished cognitive abilities.

When the researchers artificially increased FTL1 levels in young mice, their brains and behavior began to resemble that of old mice. In experiments in petri dishes, nerve cells engineered to make lots of FTL1 grew simple one-armed neural wires, or neurites, rather than the branching neurites that normal cells create.

But when scientists reduced the amount of FTL1 in the hippocampus of the old mice, they regained their youth. They had more connections between nerve cells, and the mice did better on memory tests.

“It is truly a reversal of impairments,” said Saul Villeda, PhD, associate director of the UCSF Bakar Aging Research Institute and senior author of the paper, which appears in Nature Aging on Aug. 19. “It’s much more than merely delaying or preventing symptoms.”

In old mice, FTL1 also slowed down metabolism in the cells of the hippocampus. But treating the cells with a compound that stimulates metabolism prevented these effects. Villeda is optimistic the work could lead to therapies that block the effects of FTL1 in the brain.

“We’re seeing more opportunities to alleviate the worst consequences of old age,” he said. “It’s a hopeful time to be working on the biology of aging.”

https://www.fightaging.org/archives/...aging-in-mice/

Mr.NoCredit · #2 ● 09-03-2025, 01:15 PM

Cool

IvorySmith · #3 ● 09-04-2025, 02:06 PM

I'll take it. My memory sucks.

**kellyhound** · #4 ● 09-04-2025, 03:34 PM

Harvard scientists have uncovered that lithium, a naturally occurring element in the brain, may be the missing piece in understanding Alzheimer’s.

Their decade-long research shows that lithium depletion—caused by amyloid plaques binding to it—triggers early brain changes that lead to memory loss.

By testing new lithium compounds that evade plaque capture, they reversed Alzheimer’s-like damage and restored memory in mice at doses far lower than those used in psychiatric treatments without toxicity.

Study shows for the first time that lithium plays an essential role in normal brain function and can confer resistance to brain aging and Alzheimer's disease.

Scientists discovered that lithium is depleted in the brain by binding to toxic amyloid plaques, revealing a new way Alzheimer's may begin.

What is the earliest spark that ignites the memory-robbing march of Alzheimer's disease?
Why do some people with Alzheimer's-like changes in the brain never go on to develop dementia?

These questions have bedeviled neuroscientists for decades.

Now, a team of researchers at Harvard Medical School may have found an answer: lithium deficiency in the brain.

Research shows for the first time that lithium occurs naturally in the brain, shields it from neurodegeneration, and maintains the normal function of all major brain cell types.

The findings -- 10 years in the making -- are based on a series of experiments in mice and on analyses of human brain tissue and blood samples from individuals in various stages of cognitive health.

The scientists found that lithium loss in the human brain is one of the earliest changes leading to Alzheimer's, while in mice, similar lithium depletion accelerated brain pathology and memory decline.

The team further found that reduced lithium levels stemmed from binding to amyloid plaques and impaired uptake in the brain.

In a final set of experiments, the team found that a novel lithium compound that avoids capture by amyloid plaques restored memory in mice.

The results unify decades-long observations in patients, providing a new theory of the disease and a new strategy for early diagnosis, prevention, and treatment.

Affecting an estimated 400 million people worldwide, Alzheimer's disease involves an array of brain abnormalities -- such as clumps of the protein amyloid beta, neurofibrillary tangles of the protein tau, and loss of a protective protein called REST -- but these never explained the full story of the disease.

For instance, some people with such abnormalities show no signs of cognitive decline and recently developed treatments that target amyloid beta typically don't reverse memory loss and only modestly reduce the rate of decline.

It's also clear that genetic and environmental factors affect risk of Alzheimer's, but scientists haven't figured out why some people with the same risk factors develop the disease while others don't.

Lithium, the study authors said, may be a or the critical missing link.

The study raises hopes that researchers could one day use lithium to treat the disease in its entirety rather than focusing on a single facet such as amyloid beta or tau.

One of the main discoveries in the study is that as amyloid beta begins to form deposits in the early stages of dementia in both humans and mouse models, it binds to lithium, reducing lithium's function in the brain.

The lower lithium levels affect all major brain cell types and, in mice, give rise to changes recapitulating Alzheimer's disease, including memory loss.

Treating mice with the most potent amyloid-evading compound, called lithium orotate, reversed Alzheimer's disease pathology, prevented brain cell damage, and restored memory.

Although the findings need to be confirmed in humans through clinical trials, they suggest that measuring lithium levels could help screen for early Alzheimer's.

Moreover, the findings point to the importance of testing amyloid-evading lithium compounds for treatment or prevention.

Other lithium compounds are already used to treat bipolar disorder and major depressive disorder, but they are given at much higher concentrations that can be toxic, especially to older people.

Yankner's team found that lithium orotate is effective at one-thousandth that dose -- enough to mimic the natural level of lithium in the brain. Mice treated for nearly their entire adult lives showed no evidence of toxicity.

Lithium was the only metal that had markedly different levels across groups and changed at the earliest stages of memory loss. Its levels were high in the cognitively healthy donors but greatly diminished in those with mild impairment or full-blown Alzheimer's.

The team replicated its findings in samples obtained from multiple brain banks nationwide.

The observation aligned with previous population studies showing that higher lithium levels in the environment, including in drinking water, tracked with lower rates of dementia.

But the new study went beyond by directly observing lithium in the brains of people who hadn't received lithium as a treatment, establishing a range that constitutes normal levels, and demonstrating that lithium plays an essential role in brain physiology.

"Lithium turns out to be like other nutrients we get from the environment, such as iron and vitamin C," Yankner said.

Also Scientists at UCSF have uncovered how certain immune cells in the brain, called microglia, can effectively digest toxic amyloid beta plaques that cause Alzheimer’s.

They identified a key receptor, ADGRG1, that enables this protective action. When microglia lack this receptor, plaque builds up quickly, causing memory loss and brain damage.

But when the receptor is present, it seems to help keep Alzheimer's symptoms mild.

Since ADGRG1 belongs to a drug-friendly family of receptors, this opens the door to future therapies that could enhance brain immunity and protect against Alzheimer’s in more people.

And: A quick 3-minute brainwave test called Fastball EEG can detect early signs of Alzheimer’s at home, opening the door to faster diagnoses and treatments.

The University of Bath and the University of Bristol, reports that Fastball EEG, a three-minute passive test that records electrical activity in the brain while participants view a stream of images, can reliably identify memory problems in people with Mild Cognitive Impairment (MCI) -- a condition that can lead to Alzheimer's.

This follows the group's previous study in 2021 that demonstrated Fastball was sensitive to memory impairment in Alzheimer's disease.

Crucially, the research team has demonstrated for the first time that the test can be administered in people's homes, outside of a clinical environment.

Researchers say this opens the door to wider screening and monitoring using accessible, low-cost technology.

With the development of the breakthrough Alzheimer's drugs, donanemab and lecanemab, an early diagnosis is more important than ever before.

The drugs are clinically proven to be the most effective in the early stages of Alzheimer's.

Despite this, in England, it is estimated that as many as 1 in 3 people do not currently have a dementia diagnosis, delaying treatments, support and research opportunities to tackle the condition.

Dr George Stothart, a cognitive neuroscientist in the Department of Psychology at the University of Bath said: "We're missing the first 10 to 20 years of Alzheimer's with current diagnostic tools.

Fastball offers a way to change that -- detecting memory decline far earlier and more objectively, using a quick and passive test."

Researchers say Fastball could be scaled for use in GP surgeries, memory clinics, or at home -- helping deliver earlier, more accurate diagnoses.

Dr Stothart added: "There's an urgent need for accurate, practical tools to diagnose Alzheimer's at scale. Fastball is cheap, portable, and works in real-world settings."

Fastball measures patients’ brain waves through the use of a headset that uses electroencephalogram (EEG) technology.

It records the brain's automatic response to a series of flashing images displayed on a screen.

Its inventors, from the universities of Bristol and Bath, say it can detect subtle changes to brain waves during the very early stages of dementia.

A £1.5million funding boost from the government will allow it to be tested on 1,000 patients in Bristol to find out if it can be used for mass screening.

IvorySmith · #5 ● 09-04-2025, 06:46 PM

That bit about lithium made me curious. I never heard before that lithium was in the human body. Chatgpt saves the day:

Shared Elements Between Humans and Computers

Carbon
Hydrogen
Oxygen
Nitrogen
Calcium
Phosphorus
Sulfur
Sodium
Chlorine
Potassium
Magnesium
Iron
Copper
Zinc
Manganese
Cobalt
Nickel
Molybdenum
Chromium
Boron
Iodine
Fluorine
Lithium
Arsenic
Silicon
Lead
Mercury
Tin
Aluminum — trace in humans; cases, heat sinks, alloys
Silver — trace in humans; high-conductivity traces/connectors
Gold — trace in humans; corrosion-resistant connectors/bonding
Cadmium — trace in humans; legacy batteries/pigments, some components
Antimony — trace in humans; flame-retardant synergist (Sb₂O₃) in plastics
Bromine — trace in humans; brominated flame retardants in plastics/PCBs
Titanium — trace in humans; TiO₂ pigments, BaTiO₃ ceramics (capacitors)
Barium — trace in humans; BaTiO₃ multilayer ceramic capacitors
Strontium — trace in humans; specialty glass/ceramics
Vanadium — trace in humans; alloying element in steels
Selenium — essential trace in humans; traces in some alloys/parts
Beryllium — trace in humans; Cu-Be springs/connectors
Tungsten — trace in humans; vias/contacts, weights, some components
Bismuth — trace in humans; used in some lead-free solders

A human is ~99% computer (by elemental composition).

A computer is ~95% human (by elemental composition).