Mois : novembre 2024

As the spooky season draws to a close, ghosts and ghouls are far from the most terrifying things on our minds. Just as the ancient Celts confronted the mysteries of life and death through beliefs and rituals, today’s scientists are tackling something far scarier: life itself.

Rather than ghosts or imagined spirits, the real specters we face are the biological pathways that lead to age-related decline. Longevity research is shedding light on these mechanisms, uncovering methods to slow cellular aging, repair, and extend the human healthspan.

Far from superstition, this October, longevity researchers and enthusiasts have been reshaping the future of longevity with conferences, research, funding, and the launch of new approaches.

Upcoming conferences and events

Crypto City Builders Event with Vitalia

From October 19 to November 19, Vitalia is hosting an entire month of Crypto City Builders. Designed for startup founders, techno optimists, and crypto enthusiasts, the event is set to include a Crypto Cities Summit covering the network state, new jurisdictions, and real-world building; a Safe Harbor Summit encompassing legal jurisdictions, and a crypto-driven future; and a a Hackathon and a Start-up Demo Day, ensuring that boredom is definitely not on the agenda this month. Those looking to attend can find future info here.

Shifting from sickcare to healthcare at Driving the Prevention Society and Economic conference

Collider Health’s event, Driving the Prevention Society and Economy, is a UK-focused conference intended to upturn the current, reactive ‘sickcare’ model of healthcare to a preventive model using data science and cross-sector collaboration, with a focus on broad population health improvements, with a focus on preventative treatments and proactive care. It will take place on November 12 as part of the Longevity Forum, and tickets can be bought on Eventbrite.

International Institute of Longevity hosts the Roundtable of Longevity Clinics event

On December 6 and 7, the International Institute of Longevity will bring together longevity practitioners, businesses and investors as part of the second edition of the Longevity Roundtable. This year’s event is set to cover epigenetic clocks, regenerative medicine, clinical interventions, and lifespan-extending practices like nutrition and exercise, with ticket prices ranging from $199 for virtual attendance to $999 for VIP tickets, all of which are available here.

Tech breakthroughs & new research

VitaRNA/Artan Bio advancing to preclinical studies

Having been funded via both VitaDAO directly for $91,000 and through IP tokenization at $300,000, VitaRNA/Artan Bio has reached two key project milestones, including the validation of two tRNA suppressor candidates targeting arginine nonsense mutations. By collaborating with Lonza for manufacturing, the team hopes to now test its primary candidate known as ARTAN-102 and will seek a new funding round to do so early in Q1 2025.

New research published in Nature shows AI-based approach to enhancing longevity research

The team at the Buck Institute for Research on Aging recently published a paper on the usage of machine learning to analyze metabolomic data from fruit flies and humans. This identified threonine as a key metabolite that impacts lifespan across species. It highlighted how cross-species data can be utilized to accelerate longevity research and how extensive human datasets like UK Biobank allow researchers to pinpoint metabolites such as threonine and orotate that influence aging. Read the full paper here.

DeSci and DAOs

Gamifying longevity with Pump Science

Perhaps the most novel approach to longevity funding yet, the Pump Science team is in collaboration with Molecule. As a form of ‘citizen science’, the Pump team developed a longevity prediction platform in which tokens are linked to real-world stakes in life extension compounds. The Pump.Fun token is linked to compounds that participants believe can improve lifespan. Once a market cap of $10,000 is reached for a specific compound, a ”WormBot” (AI-driven testing platform) is triggered and experiments are then run at Ora Biomedical, with results streamed to Pump Science at regular intervals. This approach hopes to draw both on crypto funding, trading, and gamification to deliver real-life results.

Hackathon time: building new longevity city solutions

Running online from November 4-11, Vitalia, the founder of the “Longevity City” on Roatan, is set to host a hackathon event dedicated to building and accelerating longevity city solutions. This event is set to take place during Vitalia’s Crypto Builders’ Month discussed above.

VitaLabs Fellowship program is now open

With the aim of attracting new and brilliant minds to longevity research, the VitaLabs team (an offshoot of VitaDAO) has launched a fellowship program to seek interested scientists for its program. This team is looking for creative, independent thinkers with PhDs and interests in entrepreneurship and longevity. Applications are open now on the site.

News and funding

$120 million in funding for Terray Therapeutics

Having launched a Series B funding round earlier this year, Terray Therapeutics has announced that it’s raised a sizable $120 million to accelerate its drug discovery platform, backed by the self-declared ‘world’s largest chemistry dataset.’ This dataset, derived from over five billion target-ligand interactions, is continuing to grow and aims to aid the fast-tracking of drug discovery for complex and age-related diseases. In addition, the team is collaborating with Calico, Google’s biotech venture, to manage the development and commercialization of drug discovery in exchange for milestone and royalty payments.

Expand Health and Humanity partner to create new platform

Humanity is the app that predicts aging and health using smart technology, and Expand Health pioneers “Longevity as a Service” via its clinic hubs using AI-backed technology. The latest announcement of a collaboration between the two may come as little surprise given the shift from traditional “sickcare” toward personalized, preventive healthcare. By using Humanity’s B2B API, the platform is designed to offer real-time insights into patients’ biological ages, providing a powerful health metric that reflects lifestyle and genetic factors more accurately than chronological age.

$1.4 billion deal as AbbVie is set to acquire Aliada Therapeutics

In a deal valued at $1.4 billion, AbbVie, a pharmaceutical research and development company, has just agreed to acquire Aliada Therapeutics, a biotech specializing in blood-brain barrier (BBB) penetration. The biotech’s lead compound, known as ALIA-1758, is designed to reduce Alzheimer’s-related amyloid plaques by targeting the transferrin receptor to cross the BBB. It is currently in clinical trials. Of course, this single product is not the only part of the deal; AbbVie expressed an interest in Aliada’s MODEL platform, which uses transferrin and CD98 receptors to deliver large biological molecules and genetic medicines into the CNS. This has potential use cases within AbbVie’s product development pipeline.

Longevity at your fingertips — literally

Finnish wearable company Oura has just announced the launch of its Oura Ring 4, a smart wearable that uses smart sensing for enhanced accuracy and personalization. Used in connection with the company’s app, the latest edition reports a 120% boost in signal quality for O2 saturation statistics and 31% fewer nighttime heart rate gaps, making it more accurate than previous models.

Social media pages to follow this month

Pump Science — crypto gaming for longevity

Lifespan Research Foundation (formerly SENS) — the latest updates from LRI

Vitalia City — feaures a whole host of events

Ora Biomedical and the Rapamycin Longevity Lab have launched a project to screen more than 600 mTOR inhibitors in the hope of finding some that are superior to geroscience’s poster child, rapamycin.

Better than chance

Rapamycin, one of the most potent compounds for prolonging lifespan in numerous animal models, was discovered serendipitously in one of the most remote locations on earth: Easter Island. The island’s name in its natives’ language is Rapa Nui, which is where “rapa” comes from. Rapamycin is produced by a certain type of soil bacteria to compete with fungi. For decades, rapamycin has been used mostly as an immunosuppressant in transplant and cancer patients before it was found that it can extend lifespan in animals.

The point is a compound discovered by chance might not be the best one for the job. Rapamycin works by inhibiting mTOR, a protein kinase that is a central regulator of nutrient sensing. However, it has its quirks and limitations. What if there are other, better mTOR inhibitors out there?

Enter Ora Biomedical, a young company focused on high-throughput screening of chemical compounds in the tiny nematode worm C. elegans. Ora uses a proprietary robotic system called WormBot. Ora’s Million Molecule Challenge is one of the most interesting crowdfunding initiatives in the longevity field. It allows anyone to buy an actual experiment for as little as 100 dollars and compete with other users while also contributing to science.

Ora’s philosophy is that the net we are currently casting to look for life-extending compounds is not nearly wide enough. Using short-lived worms and robotic systems allows us to extend the search space by orders of magnitude. The results might not necessarily be translatable to more complex animals, including humans, but the sheer volume might be able to compensate for that.

One found, 600 to go

The newest Ora’s project is a collaboration with the Rapamycin Longevity Lab led by Krister Kauppi. It entails screening more than 600 mTOR inhibitors to find the ones that work best.

“Currently, rapamycin is considered the gold standard longevity intervention – it works across many animal and even non-animal fungal models,” said Ora CEO Mitchell Lee. “The mechanism of mTOR inhibition has seen extensive development in cancer therapeutics. There’s a broad toolkit of mTOR inhibitors with different patterns of inhibition between mTOR complex 1, mTOR complex 2, and impacts on other kinases. Nobody has comprehensively looked to see if any are better than rapamycin.”

The current project began as a smaller partnership within the Million Molecule Challenge when, in an experiment funded by Kauppi and the Rapamycin Longevity Lab, Ora discovered an mTOR inhibitor that was superior to rapamycin in worms at the same dose. This molecule, called omepalisib, has already been approved by the FDA for treating certain types of cancer, so its way to the clinic as a geroprotector (anti-aging drug) might be relatively short.

The discovery of robust life extension by omepalisib gives Lee the hope that many even more promising molecules are out there. “There are at least 600 different mTOR inhibitors we could test with the WormBot platform,” he said. “We can screen through these in months, not the decades or years needed for mammalian studies, to identify what works best for extending lifespan in this system.”

Ora was spun out of Matt Kaeberlein’s laboratory at the University of Washington School of Medicine, Seattle. Kaeberlein, one of the world’s most prominent geroscientists, is a big believer in rapamycin and is currently running a rapamycin trial in dogs.

“Rapamycin is the best drug we know of to slow aging, increase lifespan, and improve healthspan,” Kaeberlein said. “There are undoubtedly other mTOR inhibitors out there that can have a similar impact, and I’m certain some of them will do even better than rapamycin. Ora’s technology affords the opportunity to find these hidden gems and develop them into the next generation of gerotherapeutics.”

Let’s go fishing!

According to the Rapamycin Longevity Lab’s white paper on the project, “There is a big gap in the literature around how good Rapamycin is compared to other mTOR inhibitors. While many mTOR inhibitors have been developed, no systematic effort exists to find the most effective mTOR inhibitors for improving healthy lifespan. This is something we need an answer to, and this project is an important first step in that direction. The end goal is improved human longevity.”

“One key reason why I founded the Rapamycin Longevity Lab was to accelerate the research around mTOR inhibition because it’s one of the most promising longevity pathways that we currently have,” Kauppi explained. “In this ambitious screening project, we aim to deliver a large volume of unique data to the longevity community with the potential to uncover new mTOR inhibitors that are even better than rapamycin. No one has done anything close to this before, and thanks to Ora Biomedical’s innovative WormBot technology, projects like this can be done in a highly efficient and cost-effective way.”

The mTOR inhibitors project is fueled by donations, and you can do your part. “Anyone can contribute through our website,” Lee said. “We hope to close the first half of financing by year-end. While it’s non-commercial initially, we’ll examine IP opportunities for the most promising compounds. Our development strategies often involve medicinal chemistry to create derivatives from lifespan-extending compounds – optimizing them for better chemical availability.”

According to Lee, the system of incentives that the longevity field is built around is the one responsible for some research directions being overlooked. “It’s striking that we’ve come this far testing only rapamycin for longevity,” he said. “It shows a misalignment between academic research and commercial/translational interests. If you proposed finding better mTOR inhibitors to the NIA (National Institute on Aging), they’d reject it for not finding new mechanisms. They’d call it a fishing expedition. Since most research relies on federal funding, important questions like identifying the best compound for this gold-standard target stagnate. That’s why Ora focuses on making these ‘fishing expeditions’ feasible – because we need to catch these fish.”

The trick-or-treaters have all gotten their candy, but age-related diseases haunt us still. Here’s what we’ve learned about them in October.

LEAF News

Team and activities

Fall Is Here, but It’s Full Steam Ahead for Lifespan.io: For those of us living in the Northern Hemisphere, the summer days are gone and the cooler days of fall have arrived. While it’s time to ditch the beachwear for chunky sweaters and a hot chocolate by the fire, things have been heating up in the longevity space.

Interviews

Life Biosciences Is Bringing Reprogramming to the Clinic: Life Biosciences is a company co-founded by the celebrity geroscientist David Sinclair and is based on his Harvard team’s research into partial cellular reprogramming.

Advocacy and Analysis

Have We Maxed Out on Life Expectancy Gains?: A new study has suggested that radical life extension is all but impossible in this century, and it has made waves among people interested in living longer.

Research Roundup

Boosting Autophagy in Astrocytes Might Help Cure Alzheimer’s: With Alzheimer’s disease, most of the focus has been on neurons. A new study’s researchers suggest boosting the process of cellular junk removal in astrocytes, brain cells that perform maintenance tasks, as a new pathway.

mTOR and SGLT-2 Inhibitors Impact Age-Related Processes: The authors of a recent review propose that there may be positive synergistic effects from combining mTOR inhibitors and sodium-glucose co-transporter-2 (SGLT-2) inhibitors.

Exercise Intensity, Duration, and Amount All Matter: In the European Journal of Protective Cardiology, researchers have published evidence that the intensity of exercise is somewhat more important than volume in reducing all-cause mortality risk, although both have significant correlations.

UK Citizens Are Healthier Than Americans, but Don’t Feel So: A new study shows that in midlife, United States citizens are less healthy than their British counterparts. The latter, however, smoke more and rate their health worse.

Senescent Macrophages: A Unique Target: In Aging, researchers have published a new study on a tool meant for analyzing macrophage senescence along with differences between inflammaging and regular inflammation.

Cryptic Exons for Targeting Neurodegenerative Disease: Amyotrophic lateral sclerosis (ALS) only affects a fraction of cells and must be treated with high specificity. Scientists have achieved that by targeting mRNA sites associated with the disease.

Astragalus Supplement Lengthens Telomeres in the Middle-Aged: Treating middle-aged people for six months with a supplement combination that included astragalus, a plant used in traditional Chinese medicine, positively impacted their telomeres.

Exosomes Break Rat Lifespan Record: In Aging Cell, researchers have published their findings that exosomes, which we have previously reported to extend the lives of mice, also extend the lives of rats.

The Chemical Reasons Why Visceral Fat Is Dangerous: In Aging Cell, researchers have described the chemical ways in which excessive visceral fat, which is metabolically active, causes oxidative stress and cellular senescence.

Heart Organoids Flown to Space Show Signs of Dysfunction: Scientists have found that human heart tissue is harmed by even a short stint in orbit. This might have implications for future space travel.

Blueberry Extract Aids Cognition in People With Inflammation: A reanalysis of data from a previous study identified a difference between people with low and high levels of inflammatory biomarkers. The cognitive performance of people with high levels of inflammation improved after they consumed anthocyanin supplements.

A Potential Target for Post-Surgery Cognitive Impairment: In Aging Cell, researchers have identified a receptor in the brain that appears to be responsible for cognitive problems after surgery, particularly in older people.

Scientists Create a Potent Bacterial Anti-Cancer Vaccine: A new study describes a novel anti-cancer vaccine based on antigen-producing bacteria that can tackle solid and metastatic cancers by colonizing tumors.

The Reason Why the p16 Senescence Pathway Exists: Researchers publishing in Aging Cell have investigated the biology of skin cells taken from people who don’t produce the senescence-related compound p16. This condition leads to familial melanoma syndrome.

Autodigestion From Gut Enzymes May Drive Aging: A new study links damage caused by digestive enzymes escaping from the gut to several hallmarks of aging. The researchers dubbed this effect “autodigestion.”

HAPLN1 in Blood Found to Rejuvenate Skin: Investigating the factors involved in skin rejuvenation processes, researchers have identified the role of hyaluronan and proteoglycan link protein 1 (HAPLN1) in restoring collagen and hyaluronic acid in aged skin.

A Senolytic Treatment for Liver Sepsis: A paper published in Aging Cell offers evidence for the idea that senolytics, which remove senescent cells, might be a treatment for acute liver sepsis and not just age-related diseases.

Neuronal Reprogramming Alleviates Alzheimer’s in Mice: Scientists have shown that long-term intermittent reprogramming limited to hippocampal neurons increases their fitness and improves cognitive function in a mouse model of Alzheimer’s disease.

The Fibroblasts That Protect Ovarian Cancer: In Aging, researchers have described a subpopulation of fibroblasts that nurture ovarian cancer tumors and shield them from harm.

NOVOS Supplement: Lifespan Extension in Male Mice: A recent preprint study suggests that a NOVOS supplement can improve healthspan and extend lifespan in male mice.

Senescent Cells Promote Cartilage Regeneration in Rats: In a rat experiment, researchers publishing in Aging Cell have found that senescent cells and SASP factors are key in regenerating knee cartilage.

Tree-based analysis of longevity predictors and their ten-year changes: a 35-Year mortality follow-up: The simultaneous examination of a broad range of potential predictors revealed that longevity can be achieved under very different conditions and is achieved by heterogeneous groups of people.

Dietary restriction impacts health and lifespan of genetically diverse mice: These findings indicate that improving health and extending lifespan are not synonymous and raise questions about which end points are the most relevant for evaluating aging interventions.

Dietary diversity contributes to delay biological aging: Dietary diversity is associated with a slower rate of biological aging, which may be due in part to reduced oxidative stress.

Association between prescription drugs and all-cause mortality risk in the UK population: As expected, most drugs were linked to a shorter lifespan, likely due to the life-limiting nature of the diseases they are prescribed to treat.

Hippocampal rejuvenation by a single intracerebral injection of one-carbon metabolites in C57BL6 old wild-type mice: The researchers propose the use of these metabolites to explore new strategies for the development of potential treatments for age-related brain diseases.

ESC-sEVs alleviate non-early-stage osteoarthritis progression by rejuvenating senescent chondrocytes: Collectively, these findings reveal that ESC-sEVs-based therapy is of high translational value in non-early-stage OA treatment.

Association of Muscle Strength With All-Cause Mortality in the Oldest Old: Prospective Cohort Study From 28 Countries: Rather than a specific threshold, muscle strength is gradually and inversely associated with mortality risk in the oldest old.

Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells: Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.

Mifepristone and rapamycin have non-additive benefits for life span in mated female Drosophila: he data suggest that mifepristone and rapamycin act through a common pathway to increase mated female Drosophila lifespan.

Machine-guided design of cell-type-targeting cis-regulatory elements: Synthetic sequences exhibit distinct motif vocabulary associated with activity in the on-target cell type and a simultaneous reduction in the activity of off-target cells.

The senolytic drug ABT-263 accelerates ovarian aging in older female mice: Senolytic drugs given to reproductively old females may adversely affect fertility.

Senescent cell transplantation into the skin induces age-related peripheral dysfunction and cognitive decline: The accumulation of senescent cells in the skin can exert remote effects on other organs, including the brain.

Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism.

News Nuggets

Lab-Grown Lung Tissue for Diseases and Transplants: Frontier Bio Corporation has announced a groundbreaking achievement in lab-grown lung tissue. By combining 3D bioprinting with the ability of stem cells to self-assemble, mimicking natural organ development, the California-based biotech company has created complex microscale lung tissue.

Solve Aging and Enhance Brains at MIT: It might take a second renaissance bringing polymaths across science to solve aging and enhance human mental capacity to groundbreaking heights. From 10/25 to 10/27, Ekkolápto, Augmentation Lab, and Meditation Artifacts united interdisciplinary minds.

Grant Awarded for Heart Aging at the University of Oxford: The Longevity Science Foundation (LSF), a nonprofit organization dedicated to funding research aimed at extending the healthy human lifespan, is proud to announce a grant award to researchers at the University of Oxford’s Department of Physiology, Anatomy, and Genetics.

World’s First Subzero Organ Transports: In a world first, a pig kidney preserved at subzero temperatures was successfully transported across the Atlantic Ocean multiple times, demonstrating the potential for a novel technology to greatly extend organ storage and preservation, and make long-distance organ transportation a clinical reality.

Coming Up

Longevity Summit Dublin 2025 Announces New Dates and Venue: Longevity Summit Dublin, the premier international event dedicated to the latest research, innovation, and collaboration in the field of longevity, is excited to announce its new dates and venue for 2025.