Saudi Arabia to Spend $1 billion a Year to Slow Aging

Anyone who has more money than they know what to do with eventually tries to cure aging. Google founder Larry Page has tried it. Jeff Bezos has tried it. Tech billionaires Larry Ellison and Peter Thiel have tried it. Now the kingdom of Saudi Arabia, which has about as much money as all of them put together, is going to try it. The Saudi royal family has started a not-for-profit organization called the Hevolution Foundation that plans to spend up to $1 billion a year of its oil wealth supporting basic research on the biology of aging and finding ways to extend the number of years people live in good health, a concept known as “health span.”

The sum, if the Saudis can spend it, could make the Gulf state the largest single sponsor of researchers attempting to understand the underlying causes of aging—and how it might be slowed down with drugs. The foundation hasn’t yet made a formal announcement, but the scope of its effort has been outlined at scientific meetings and is the subject of excited chatter among aging researchers, who hope it will underwrite large human studies of potential anti-aging drugs. The fund is managed by Mehmood Khan, a former Mayo Clinic endocrinologist and the onetime chief scientist at PespsiCo, who was recruited to the CEO job in 2020. ““Our primary goal is to extend the period of healthy lifespan,” Khan said in an interview. “There is not a bigger medical problem on the planet than this one.

The idea, popular among some longevity scientists, is that if you can slow the body’s aging process, you can delay the onset of multiple diseases and extend the healthy years people are able to enjoy as they grow older. Khan says the fund is going to give grants for basic scientific research on what causes aging, just as others have done, but it also plans to go a step further by supporting drug studies, including trials of “treatments that are patent expired or never got commercialized.”

We need to translate that biology to progress towards human clinical research. Ultimately, it won’t make a difference until something appears in the market that actually benefits patients,” Khan says.

Khan says the fund is authorized to spend up to $1 billion per year indefinitely, and will be able to take financial stakes in biotech companies. By comparison, the division of the US National Institute on Aging that supports basic research on the biology of aging spends about $325 million a year.

Hevolution hasn’t announced what projects it will back, but people familiar with the group say it looked at funding a $100 million X Prize for age reversal technology and has reached a preliminary agreement to fund a test of the diabetes drug metformin in several thousand elderly people.

That trial, known as “TAME” (for “Targeting Aging with Metformin”), has been touted as the first major test of any drug to postpone aging in humans, but the study has languished for years without anyone willing to pay for it.

Source: https://www.technologyreview.com/

Memory Problems Common in Old Age Can Be Reversed

While immortality might forever be out of reach, a long, healthy retirement is the stuff dreams are made of. To that end, a recent study suggests that the kinds of memory problems common in old age can be reversed, and all it takes is some cerebrospinal fluid (CSF) harvested from the young. In mice, at least.

If this is sounding a little familiar, you might be thinking of a similar series of studies done back in the mid-2010s, which found that older mice could be generally ‘rejuvenated‘ with the blood of younger animals – both from humans and from mice. The FDA even had to warn people to stop doing it. This new study instead examined the links between memory and cerebrospinal fluid  (CSF), and the results show considerable promise, even providing a mechanism for how it works, and highlighting a potential growth factor that could mimic the results.

“We know that CSF composition changes with age, and, in fact, these changes are used routinely in the clinic to assess brain health and disease biomarkers,” Stanford University neurologist Tal Iram said. “However, we don’t know well how these changes affect the function of the cells in the aging brain.

To investigate, the researchers, led by Iram, took older mice (between 18–22 months old) and gave them light shocks on the foot, at the same time as a tone and flashing light were activated. The mice were then split into groups, and either given young mouse CSF (from animals 10 weeks old) or artificial CSF. In experiments like this, if the mice ‘freeze’ when they see the tone and light, it means they’re remembering the foot shock, and are preparing for it to happen again. In this study, three weeks after the foot shocks were conducted (which the team called “memory acquisition“), the researchers tested the mice, finding that the animals that had been given the CSF from young mice showed higher-than-average freezing rates, suggesting they had better memory. This was followed up by a battery of other experiments to test the theory, which revealed that certain genes (that are different in young-versus-old CSF) could be used to get the same response. In other words, without needing to extract someone’s brain fluid.

When we took a deeper look into gene changes that occurred in the hippocampus (a region associated with memory and aging-related cognitive decline), we found, to our surprise, a strong signature of genes that belong to oligodendrocytes,” Iram explained. “Oligodendrocytes are unique because their progenitors are still present in vast numbers in the aged brain, but they are very slow in responding to cues that promote their differentiation. We found that when they are re-exposed to young CSF, they proliferate and produce more myelin in the hippocampus.” Oligodendrocytes are particularly helpful because they produce myelin, a material that covers and insulates neuron fibers.

New Drug Could Protect Against Aging

Senolytics are an emerging class of drugs designed to target zombie-like cells that have stopped dividing and build up in the body as we age, and the past few years have seen some exciting discoveries that demonstrate their potential. Adding another to the list are Mayo Clinic researchers, who have shown that these drugs can protect against aging and its related diseases, by acting on a protein long associated with longevity. The zombie-like cells involved in this research are known as senescent cells, and their accumulation during aging is associated with a range of diseases. Recent studies have shown that using senolytics to clear them out could serve as new and effective treatments for dementia and diabetes, and also improve health and lifespan more broadly.

The Mayo Clinic team were exploring how senolytics can influence levels of a protein called a-klotho, known to help protect older people from the effects of aging. The role of this protein in the aging process is well established and has placed it at the center of much research in this space, with studies demonstrating how it could help reverse osteoarthritis and regenerate old musclesLevels of a-klotho are also known to decrease with age, and studies have shown these declines shorten the lifespan of mice. Conversely, inserting genes that encode for the protein has been shown to increase the lifespan of mice by 30 percent. Boosting its levels in humans has been problematic, however, as its larger size would require it to be administered intravenously. But now the Mayo Clinic scientists believe they have found another route, as senolytic drugs can be administered orally.

They first showed that senescent cells reduce levels of a-klotho in human cells. They then demonstrated that using a combination of senolytic drugs on three different types of mice could counter this and increase levels of a-klotho. This effect was then observed in follow-up experiments on patients with idiopathic pulmonary fibrosis, a lung disease that can cause breathing difficulty, frailty and death.

“We show that there is an avenue for an orally active, small-molecule approach to increase this beneficial protein and also to amplify the action of senolytic drugs,” says James Kirkland, M.D., Ph.D., a Mayo Clinic internist and senior author of the study.

Source: https://www.thelancet.com/

The Fountain of Youth

A step toward discovering the fountain of youth could involve protecting against the inevitable accumulation of “senescentcells associated with aging and age-related diseases. Now, researchers from Japan have identified the MondoA protein as key to protecting against the accumulation of senescent cells.

In a study published this month in Cell Reports, researchers led by Osaka University have shown that MondoA delays cellular senescence, and therefore promotes longevity, by activating . Autophagy is a process whereby cells undergo controlled breakdown and recycling of their components, which is important for maintaining stable conditions in the cellular environment and for enabling adaptation to stress. Activation of autophagy by MondoA partly involves suppressing a protein called Rubicon, which is a negative regulator of autophagy. Rubicon can increase with aging in various tissues and model organisms, which can cause the decline in autophagy seen with aging.

Furthermore, MondoA is also essential to maintaining stable conditions of parts of the cell called mitochondria, which are responsible for energy production. MondoA does this by regulating another molecule, Prdx3, which is involved in mitochondrial turnover. Mitochondria are constantly fusing and dividing, which is important for maintaining their health. Prdx3 is part of the process by which autophagy occurs in mitochondria, preventing senescence. The research team led by Osaka University concluded that MondoA plays a key role in the regulation of Prdx3 and therefore in maintaining mitochondrial stability.

Particularly dense accumulation of senescent cells has been observed in the kidney. The researchers therefore looked at ischemic acute kidney injury (AKI) in mice.

Mice with ischemic AKI and reduced levels of MondoA showed increased senescence,” explains lead author Hitomi Yamamoto-Imoto. “We also found that decreased MondoA in the nucleus correlated with human aging and ischemic AKI. MondoA therefore counteracts cellular  in aging and ischemic AKI in both mice and humans.”

Drugs that eliminate senescent cells, called senolytics, are currently being considered as treatment for age-associated diseases. However, senescent  play important roles, and their complete removal may have considerable side effects. “Our work shows that the transcriptional activation of MondoA can protect against , kidney injury associated with aging, and organismal aging,” explains senior author Tamotsu Yoshimori. “Activation of MondoA and therefore autophagy could be a potentially safe therapeutic strategy.” This work could well open new and safer avenues for the treatment of aging and age-related diseases.

Source: https://phys.org/

How to Reverse Muscle Loss Due to Aging

An international team led by uOttawa Faculty of Medicine researchers have published findings that could contribute to future therapeutics for muscle degeneration due to old age, and diseases such as cancer and muscular dystrophyIn a study appearing in the Journal of Cell Biology, which publishes peer-reviewed research on cellular structure and function, the authors said their work demonstrates the importance of the enzyme GCN5 in maintaining the expression of key structural proteins in skeletal muscle. Those are the muscles attached to bone that breathing, posture and locomotion all rely on.

We found that if you delete GCN5 expression from muscle it will no longer be able to handle extreme physical stress,” says Dr. Keir Menzies, a molecular biologist at the Faculty of Medicine’s Biochemistry, Microbiology and Immunology department and cross-appointed as an associate professor at the Interdisciplinary School of Health Sciences.

Over the span of roughly five years, the uOttawa-led international collaboration painstakingly experimented with a muscle-specific mouse knockout” of GCN5, a well-studied enzyme which regulates multiple cellular processes such as metabolism and inflammation. Through a series of manipulations, scientists produce lab mice in which specific genes are disrupted, or knocked out, to unveil animal models of human disease and better understand how genes work.

In this case, multiple experiments were done to examine the role the GCN5 enzyme plays in muscle fiber. What they found with this line of muscle-specific mouse knockouts was a notable decline in muscle health during physical stress, such as downhill treadmill running, a type of exercise known by athletes to cause micro-tears in muscle fibres to stimulate muscle growth. The lab animals’ muscle fibers became dramatically weaker as they scurried downhill, like those of old mice, while wild-type mice were not similarly impacted

Dr. Menzies, the senior author of the study, says the findings are akin to what is observed in advanced aging, or myopathies and muscular dystrophy, a group of genetic diseases that result in progressive weakness and loss of muscle mass. It was supported by human data, including an observed negative correlation between muscle fiber diameter and Yin Yang 1, a highly multifunctional protein that is pivotal to a slew of cellular processes and found by the Menzies lab to be a target of GCN5. Ultimately, the team’s research found that GCN5 boosts the expression of key structural muscle proteins, notably dystrophin, and a lack of it will reduce them.

Source: https://rupress.org/
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https://www.thebrighterside.news

Rejuvenation by Controlled Reprogramming

On 19 January 2022, co-founders Rick Klausner and Hans Bishop publicly launched an aging research initiative called Altos Labs, with $3 billion in initial investment from backers including tech investor Yuri Milner and Amazon founder Jeff Bezos. This is the latest in a recent surge of investment in ventures seeking to build anti-aging interventions on the back of basic research programs looking at epigenetic reprogramming. In December, cryptocurrency company Coinbase’s cofounder Brian Armstrong and venture capitalist Blake Byers founded NewLimit, an aging-focused biotech backed by an initial $105 million investment, with the University of California, San Francisco’s Alex Marson and Stanford’s Mark Davis as advisors.

The discovery of the Yamanaka factors’ — four transcription factors (Oct3/4, Sox2, c-Myc and Klf4) that can reprogram a differentiated somatic cell into a pluripotent embryonic-like state — earned Kyoto University researcher Shinya Yamanaka a share of the Nobel prize in 2012. The finding, described in 2006, transformed stem cell research by providing a new source of embryonic stem cell (ESC)-like cells, induced pluripotent stem cell (iPSCs), that do not require human embryos for their derivation. But in recent years, Yamanaka factors have also become the focus for another burgeoning area: aging research.

So-called partial reprogramming consists in applying Yamanaka factors to cells for long enough to roll back cellular aging and repair tissues but without returning to pluripotency. Several groups, including those headed by Stanford University’s Vittorio Sebastiano, the Salk Institute’s Juan Carlos Izpisúa Belmonte and Harvard Medical School’s David Sinclair, have shown that partial reprogramming can dramatically reverse age-related phenotypes in the eye, muscle and other tissues in cultured mammalian cells and even rodent models by countering epigenetic changes associated with aging. These results have spurred interest in translating insights from animal models into anti-aging interventions. “This is a pursuit that has now become a race,” says Daniel Ives, CEO and founder of Cambridge, UK-based Shift Bioscience.

The Yamanaka factors that can reprogram cells into their embryonic-like state are at the heart of longevity research

We’re investing in this area [because] it is one of the few interventions we know of that can restore youthful function in a diverse set of cell types,” explains Jacob Kimmel, a principal investigator at Alphabet subsidiary Calico Life Sciences in South San Francisco, California. The zeal is shared by Joan Mannick, head of R&D at Life Biosciences, who says partial reprogramming could be potentially “transformative” when it comes to treating or even preventing age-related diseases. Life Biosciences, a startup co-founded by David Sinclair, is exploring the regenerative capacity of three Yamanaka factors (Oct4, Sox2 and Klf4).

Source: https://www.nature.com/

Flexible device could treat hearing loss without batteries

Some people are born with hearing loss, while others acquire it with age, infections or long-term noise exposures. In many instances, the tiny hairs in the inner ear’s cochlea that allow the brain to recognize electrical pulses as sound are damaged. As a step toward an advanced artificial cochlea, researchers in ACS Nano report a conductive membrane, which translated sound waves into matching electrical signals when implanted inside a model ear, without requiring external power.

An electrically conductive membrane implanted inside a model ear simulates cochlear hairs by converting sound waves into electrical pulses; wiring connects the prototype to a device that collects the output current signal.

When the hair cells inside the inner ear stop working, there’s no way to reverse the damage. Currently, treatment is limited to hearing aids or cochlear implants. But these devices require external power sources and can have difficulty amplifying speech correctly so that it’s understood by the user. One possible solution is to simulate healthy cochlear hairs, converting noise into the electrical signals processed by the brain as recognizable sounds. To accomplish this, previous researchers have tried self-powered piezoelectric materials, which become charged when they’re compressed by the pressure that accompanies sound waves, and triboelectric materials, which produce friction and static electricity when moved by these waves. However, the devices aren’t easy to make and don’t produce enough signal across the frequencies involved in human speech. So, Yunming Wang and colleagues from the University of Wuhan wanted a simple way to fabricate a material that used both compression and friction for an acoustic sensing device with high efficiency and sensitivity across a broad range of audio frequencies.

To create a piezo-triboelectric material, the researchers mixed barium titanate nanoparticles coated with silicon dioxide into a conductive polymer, which they dried into a thin, flexible film. Next, they removed the silicon dioxide shells with an alkaline solution. This step left behind a sponge-like membrane with spaces around the nanoparticles, allowing them to jostle around when hit by sound waves. In tests, the researchers showed that contact between the nanoparticles and polymer increased the membrane’s electrical output by 55% compared to the pristine polymer. When they sandwiched the membrane between two thin metal grids, the acoustic sensing device produced a maximum electrical signal at 170 hertz, a frequency within the range of most adult’s voices. Finally, the researchers implanted the device inside a model ear and played a music file. They recorded the electrical output and converted it into a new audio file, which displayed a strong similarity to the original version. The researchers say their self-powered device is sensitive to the wide acoustic range needed to hear most sounds and voices.

Source: https://www.acs.org/
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https://pubmed.ncbi.nlm.nih.gov/

Toxic Fatty Acids Play a Critical Role in Brain Cell Death

Rodent studies led by researchers at NYU Grossman School of Medicine have found that cells called astrocytes, which normally nourish neurons, also release toxic fatty acids after neurons are damaged. The team suggests that this phenomenon is likely the driving factor behind most, if not all, diseases that affect brain function, as well as the natural breakdown of brain cells seen in aging.

Our findings show that the toxic fatty acids produced by astrocytes play a critical role in brain cell death and provide a promising new target for treating, and perhaps even preventing, many neurodegenerative diseases,” said Shane Liddelow, PhD, who is co-senior and corresponding author of the researchers’ published paper in Nature. In their report, which is titled, “Neurotoxic reactive astrocytes induce cell death via saturated lipids,” the team concluded. “The findings highlight the important role of the astrocyte reactivity response in CNS injury and neurodegenerative disease and the relatively unexplored role of lipids in CNS signaling.”

 

Astrocytes—star-shaped glial cells of the central nervous system (CNS)—undergo functional changes in response to CNS disease and injury, but the mechanisms that underlie these changes and their therapeutic relevance remain unclear, the authors noted. Interestingly, previous research has pointed to astrocytes as the culprits behind cell death seen in Parkinson’s disease and dementia, among other neurodegenerative diseases. “Astrocytes regulate the response of the central nervous system to disease and injury, and have been hypothesized to actively kill neurons in neurodegenerative disease,” the researchers stated. But while many experts believed that these cells release a neuron-killing molecule to clear away damaged brain cells, the identity of the toxin has remained a mystery.

The studies by Liddelow and colleagues now provide what they say is the first evidence that tissue damage prompts astrocytes to produce two kinds of fats, long-chain saturated free fatty acids and phosphatidylcholines. These fats then trigger cell death in damaged neurons. For their investigation, researchers analyzed the molecules released by astrocytes collected from rodents. “Previous evidence suggested that the toxic activity of reactive astrocytes is mediated by a secreted protein, so we first sought to identify the toxic agent by protein mass spectrometry of reactive versus control astrocyte conditioned medium (ACM),” they wrote.

Source: https://www.genengnews.com/

How to Reverse Age-related Brain Deterioration

Research from APC Microbiome Ireland (APCSFI Research Centre at University College Cork (UCC) published in the journal Nature Aging introduces a novel approach to reverse aspects of aging-related deterioration in the brain and cognitive function via the microbes in the gut.

As our population ages one of the key global challenges is to develop strategies to maintain healthy brain function. This ground-breaking research opens up a potentially new therapeutic avenues in the form of microbial-based interventions to slow down brain aging and associated cognitive problems. The work was carried out by researchers in the Brain-Gut-Microbiota lab in APC led by Prof John F. Cryan, Vice President for Research & Innovation, University College Cork as well as a Principal Investigator at APC Microbiome Ireland an SFI Research Centre, based in in University College Cork and Teagasc Moorepark.

There is a growing appreciation of the importance of the microbes in the gut on all aspects of physiology and medicine. In this latest mouse study the authors show that by transplanting microbes from young into old animals they could rejuvenate aspects of brain and immune function.

Prof John F. Cryan, says “Previous research published by the APC and other groups internationally has shown that the gut microbiome plays a key role in aging and the aging process. This new research is a potential game changer , as we have established that the microbiome can be harnessed to reverse age-related brain deterioration. We also see evidence of improved learning ability and cognitive function”.

Although very exciting Cryan cautions that “it is still early days and much more work is needed to see how these findings could be translated in humans”.

APC Director Prof Paul Ross stated that “This research of Prof. Cryan and colleagues further demonstrates the importance of the gut microbiome in many aspects of health, and particularly across the brain/gut axis where brain functioning can be positively influenced. The study opens up possibilities in the future to modulate gut microbiota as a therapeutic target to influence brain health”.

The study was led by co-first authors Dr Marcus Boehme along with PhD student Katherine E. Guzzetta, and Dr Thomaz Bastiaanssen.

Source: https://www.ucc.ie/

Reversal of Aging is Closer

The cure for aging has long been the Holy Grail of medicine. Emerging technologies, like the gene editing tool CRISPR, have opened the floodgates to what may be possible for the future of medical science. The key to slowing down aging, however, may lie in a simple and age-old technique. For the first time, Israeli scientists showed the reversal of aging in two key biological clocks in humans, by giving patients oxygen therapy in a pressurized chamber. The results appear in the journal Aging.

As you grow older and your cells continue to divide, sequences of DNA at the end of chromosomes, called telomeres, gradually become shorter. Once the telomeres become too short, the cell can no longer replicate and eventually dies. This isn’t necessarily a bad thing.

Telomere shortening can prevent rogue cancerous cells from multiplying uncontrollably, but unfortunately, this comes with the cost of genetic aging. These geriatric cells that can no longer divide are also known as senescent cells, which accumulate over the period of your life and are believed to be one of the leading causes of aging. In a clinical trial, 35 healthy adults aged 64 and older received 60 oxygen therapy sessions daily over the course of three months. The scientists collected the subjects’ blood samples prior to treatment, after the first and second months of the trial, and two weeks after the trial was over. None of the patients had any lifestyle, diet, or medication changes throughout the study, and yet their blood work showed significant increases in the telomere length of their cells and a decrease in the number of their senescent cells. This isn’t the first time doctors have put patients into pressurized oxygen chambers. Hyperbaric oxygen therapy (HBOT) has been used for almost a century to treat a number of illnesses, including decompression sickness in deep-sea divers and carbon monoxide poisoning.

The therapy involves breathing pure oxygen in a pressurized chamber, which causes blood and tissues in your body to become saturated with oxygen. Strangely enough, this can trigger similar physiological effects that occur when your body is starved of oxygen, known as hypoxia. While previous research shows these effects can stimulate your brain and increase your cognitive abilities, this is the first study to show the therapy may also reverse aging.

Since telomere shortening is considered the ‘Holy Grail’ of the biology of aging, many pharmacological and environmental interventions are being extensively explored in the hopes of enabling telomere elongation,” said study coauthor Shai Efrati, a professor at the Sackler School of Medicine at Tel Aviv University. The significant improvement of telomere length shown during and after these unique HBOT protocols provides the scientific community with a new foundation of understanding that aging can, indeed, be targeted and reversed at the basic cellular-biological level.

This also isn’t the first time scientists have claimed to reverse aging. Several studies using pharmacological drugs, such as danazol, have been shown to elongate telomeres. Additionally, lifestyle changes, including exercise and healthy diets, have been shown to have small effects on the growth of telomeres. “Until now, interventions such as lifestyle modifications and intense exercise were shown to have some inhibition effect on the expected telomere length shortening. However, what is remarkable to note in our study, is that in just three months of HBOT, we were able to achieve such significant telomere elongation—at rates far beyond any of the current available interventions or lifestyle modifications,” study coauthor Amir Hadanny, a neurosurgeon at the Sagol Center of Hyperbaric Medicine and Research in Israel, explained in the press release.

Source: https://www.popularmechanics.com/