Timofey Glinin:

Today, my pride knows no bounds. For almost three years, the Open Longevity project dedicated itself to constructing a comprehensive database, capturing every facet of how genes influence aging. The Open Genes endeavor wasn't a walk in the park: it demanded immense dedication, a harmonious collaboration between software developers and aging biologists. And now, our tireless efforts have culminated in a groundbreaking scientific publication in one of the world's leading scientific journals—Nucleic Acid Research.

This achievement primarily stands as a testament to the relentless drive and dedication of Ekaterina Rafikova and Constantine Rafikov, who poured their heart and soul into this database. Mikhail Batin and Anastasia Egorova who inspired us to make our dreams to reality. But I must admit, it brings joy to my heart too. As the scientific lead at Open Longevity, we've demonstrated our capability to produce monumental cornerstones for the entire industry.

Within this database, we've meticulously curated more than 2,000 genes, detailing their contribution to lifespan alteration, their influence on aging pathways, and identifying specific variants associated with longevity.

Scientific articles are diverse, and the painstaking task of standardization often had to be done by hand. But now, we've birthed a tool that enables us to bioinformatically compare the contributions of these genes, and to hunt for combinations of genetic interventions.

We've proven what we're capable of, but this platform's journey is just beginning. The horizon brims with exciting ideas: like launching bioinformatic competitions based on Open Genes, incorporating more information on protein interactions, and so much more. And as daunting as these tasks may sound, they are surmountable, especially with the backing of the most passionate anti-aging community out there.

Hey there longevity ppl all over the world! October 1 is the International Lonngevity Day (and October is the longevity month, so more longevity events are coming). There are and will be meetings in 🇺🇸San Francisco and New York, 🇮🇱Tel Aviv, 🇪🇸Madrid, 🇧🇪Brussels, 🇲🇪Budva, 🇫🇮Helsinki, 🇩🇪Berlin, and many more! Details are here.

Budva meeting is here https://facebook.com/events/s/longevity-day--montenegro/2514408125390283/?mibextid=RQdjqZ

This Saturday, Oct 7, 12:00 at Ferry Building in San Francisco (where International Longevity Day was held last Sunday) Lets collect some signatures! smart signs only😎 dublinlongevitydeclaration.org/#DublinLongevityDeclaration #SayForeverDayOct7 #SayForeverDay

The first Baltics Conference on Healthy Longevity, organized by the Longevity Alliance Baltic (LAB) will take place on 25 November 2023 (11.00-17.00) in the Latvian University – House of Nature, in Riga, Latvia.

Some of the leading longevity researchers and advocates in the Baltic area and internationally will take part. Hopefully, this conference will help increase the awareness about longevity research and help build up the longevity community in the Baltic region, catalyzing a further development of the longevity field internationally.

Details and registrations are in the link. The attendance is free, but registration is requested. The program is preliminary and changes may be possible. Thanks for spreading the word!

http://longevitybaltics.org/conference/

Halloween is on the horizon, and this month, we're drawing inspiration from the Day of the Dead. Let's gather at the Ferry Bld in San Francisco on Saturday, October 28 at 4 PM. For now we are planning to walk to the Fisherman's Wharf or Presidio along the embankment.

Event Concept is Expelling the Inner Death.

We will conduct a symbolic exorcism ritual, channeling energy to challenge the belief that death is our ultimate destiny.

In an age marked by revolutionary breakthroughs, from genome-editing therapies to cellular reprogramming, we're redefining our relationship with mortality. As societal perceptions shift, ceremonies like ours capture the essence of this transformation. The strength of our gathering magnifies the magic we can create. Circle this date on your calendar and be part of this transformative event.

Own a coffin? Feel free to bring it. Or any other emblem that represents your reflections on death or your stand against it.

Costume Call: To effectively illustrate the concept of expelling death from our lives, we're calling for 2 costume themes:

🎃Dress in costumes that encapsulate deeper connotations of death—whether it's damaged mitochondria, cholesterol, genetic mutations, or society's evolving views on mortality.

🎃Dress in costumes of characters that expel death in different cultures, existing or fictional: monks, shamans, priests, elve healers, etc. Bring tambourines and other music instruments that can help assist with the rituals and attract attention.

Raise your anti-death banners and bring posters that celebrate life. We'll also be collecting signatures for the Dublin Longevity Declaration. With video recording in place, we aim to make this event unforgettable.

Want a deeper involvement? If you're interested in assisting with event preparations and organization, don't hesitate to get in touch.

Together, let's make this Halloween a symbol of hope for scientific approach, and a declaration of triumph over death within ourselves.

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Aging is a paradox. A squirrel can live for 20 years, while the rat - only for two years, and we do not know why. Birds and bats live very long for their body sizes. The termite queen can live for many decades, while the worker termite is short-lived while having the same genome. Naked mole rats are barely age at all, while some carnivorous marsupials and Pacific salmons die very soon after reproduction, and we don't why.

Aging is a routine part of our existence but it does not have a scientific definition. We know that bad things happen to organisms as they age, but what exactly happens and why, remains obscure. If we ask different experts what aging is, they will give us different answers. The consensus around this question is missing. In this seminar, we will discuss the strengths and the weaknesses of the mainstream models explaining the evolution of aging. Peter will present his alternative model, which suggests that aging evolved as an adaptive mechanism to control the spread of infectious diseases.

us06web.zoom.us/j/84240186900

Nastya Egorova: Made a very important step towards decentralized clinical trials with these wonderful ppl the other day aka built a Telegram bot for trial participants. We also took the🥇at the #DeSci track at #ZuConnect hackathon🤓 love you guys, excited to build this thing (and the whole infrastructure) bigger🙌 Zuzalu community and web3 in general are perfect to make such initiatives finally happen🚀

Check out Aaron King’s project:

“It took longer than it should have, but Agerank.com is now functional. It's not done but at least it's shareable.

"If it changes with age, it's part of aging."

Search for biomarkers in the top bar, use demographic filters in the left bar. Input your own data using the Plot function next to each scatterplot, add more datapoints with +. Swap medical ranges and underlying scatterplot info using the dropdown menus.

What it does:
- Shows most of the NHANES biomarkers in the context of age. How does each biomarker change over the lifespan, what is the variance, what are some medical ranges that exist for that biomarker.
- Allows you to input your own data to see if you are beating the curve.
- Allows you to swap between various years of NHANES data, not all data has been put in yet.
- Has demographics filters for gender, ethnicity, BMI, and wealth.
- Displays floating point mean (red) and median (black)

Now I have a list of all the biomarkers that change with age, at least biomarkers from NHANES. I've discovered that 6 biomarkers are pretty much explained by obesity, so if you don't get fat these 6 will not change over your life. Another 8 respond to obesity but are not fully explained by it.

At least 178 biomarkers in the system so far. More incoming.”

The first real antiaging drug has just received FDA approval:

"Today, I’m so proud to announce that Loyal has earned what we believe to be the FDA’s first-ever formal acceptance that a drug can be developed and approved to extend lifespan. In regulatory parlance, we have completed the technical effectiveness portion of our conditional approval application for LOY-001’s use in large dog lifespan extension.

As there was no established regulatory path for a lifespan extension drug, we had to design from scratch a scientifically strong and logistically feasible way to demonstrate efficacy of an aging drug. This process took more than four years, resulting in the 2,300+ page technical section now approved by the FDA. It included interventional studies of LOY-001 in an FDA-accepted model of canine aging and an observational (no-drug) study of 451 dogs.

Our interventional studies with LOY-001 showed that the drug improved clinically-relevant aging parameters. We assessed these in laboratory studies using a dog model that represents accelerated aging. We then correlated those results with quality of life scores in the observational study, as independently measured by dog owners, and health outcomes as measured by veterinarians. This was key to show that the biological benefits of the drug are linked to clinically relevant outcomes.

From our data, the FDA believes LOY-001 is likely to be effective for large dog lifespan extension in the real world. Once we satisfactorily complete safety and manufacturing sections and other requirements, vets will be able to prescribe LOY-001 to extend the lifespan of large dogs while we complete the confirmatory pivotal lifespan extension study in parallel."

~ Celine Halioua, founder of Loyal

From Karl Pfleger’d LinkedIn:

Data from the new TargetD trial suggests that prior vitamin D trials were flawed.

Many people, even professionals, still think vitamin D was a false profit that was disproven by big RCTs. This view is very flawed, for several reasons. A brief history:

For decades, thousands of studies have shown reliable correlation of low vitamin D levels & bad health outcomes. Scientifically, the proper way to test the hypothesis that this correlation is causal is RCTs that meaningfully alter the low vitamin D status & then measure outcomes.

Heaney in 2014 published trial design guidelines for nutrients saying essentially the above.

Rule 4 was "The hypothesis to be tested must be that a change in nutrient status (not just a change in diet) produces the sought-for effect."

This trial design guideline was repeated in 2018 specifically for vitamin D by Grant et al. But almost every negative vitamin D trial violates these guidelines & fails to properly scientifically test the hypothesis.

In 2020 Boucher specifically & directly addressed this issue in a short paper, "Why do so many trials of vitamin D supplementation fail?"

Common simple D RCT flaws:
- Not starting w/ subjects w/ low levels.
- Not using high enough dose to meaningfully change status (eg resolve deficiency). Esp true w/ overweight subjects who need higher doses.
- Not waiting long enough for levels to rise before measuring outcomes.

Now a new trial called Target-D tries to do the right thing by repeatedly testing 25OHD until a prespecified target (40ng/ml) is achieved & early data presented at American Heart Association's Nov'23 meeting vindicates the criticisms of the prior trials.

Outcome data not mentioned (prob not avail yet) but data f/ early dosing still shows the issues:

On dose: "90% [of subjects] required some level of Vitamin D dosing. Of those, 86.5% required more than 2000 IU daily [VITAL study dose] and 14.6% required more than 10,000 IU daily"

On how long it took: "Less than 65% achieved over 40 ng/mL at three months. Another 25% of patients required six months or more of dosing titration" So longer than most D RCTs wait to measure outcomes, usually w/o testing levels achieved. Shows mid-trial testing is important.

"Our findings here show that just giving patients some Vit D does not help them achieve optimal levels"

Just b/c a trial is big doesn't mean it answers the right question. Most failed D trials don't negate the hypothesis that raising levels f/ low to sufficient improves health.

The central effort in promoting life extension revolves around broadcasting scientific achievements in this field.

The battle against aging often boils down to a newsfeed of scientific discoveries.

Thousands of people, across various platforms like Twitter, review articles, and YouTube, relay what gerontology researchers have discovered.

Among Longevity activists, there's a prevailing idea of alerting the public about the imminent discovery of anti-aging remedies.

However, there's a problem. This approach isn't really effective.

The efficiency of such popularization is probably less than 1%. Discussions about a few molecules and their interactions related to aging lead nowhere.

There are millions of such publications. It's like a chewing gum that people have been chewing for decades. How many interviews with leading experts do we need to realize that they have minimal impact?

I'm not against scientific news, interviews, or statements on the necessity of life extension. I strongly support them, but they are insufficient. This activity becomes harmful if we focus solely on it, as it drains the energy and strength needed for change.

It creates an illusion of progress, as if we've convinced someone to take action.

If we had a metric for social change, we would see the minimal impact of such work.

People are not rational. In a rational world, one interview, one lecture, one book would be enough to make life extension a universal social task. Moreover, in a society that accepts death, there are groups with entirely different interests, monopolizing resources and reluctant to allocate them to life extension.

There are people, knowingly or unknowingly, who promote death. Even under the banners of health preservation and life extension, there can be enemies whose true interest is personal enrichment. Selling promises of immediate life extension works well, even for non-effective remedies.

Overcoming tradition, stereotypes, and indifference involves incredibly complex tasks, the solutions to which are not just about listing aging science achievements.

Clearly, we need a different approach in the public sphere.

How?

Raise the level of abstraction, introduce new categories, use models of social processes, gather and analyze new types of data.

What's the first step? Change the language in which we discuss these problems. Introduce new categories, describe reality anew.

Like in mathematics, where we can't solve a vast class of problems using only arithmetic and require differential and integral calculus.

Like in physics, where we need a counterintuitive view of the world, where the passage of time depends on the speed of movement, or events in the quantum world completely contradict common sense. But this brings us closer to understanding the nature of reality.

Rationalists, in solving their problems, introduced several concepts, particularly CEV (coherent extrapolated volition) — how future AI will extrapolate our values.

Effective altruists think in terms of calculating expected utility and overlooked efficient ways of doing good.

Whenever we face complex new tasks, we need new categories, essentially a new language, to solve this new challenge.

What specific categories do we need?

We need a measure of readiness to act in the fight against death. The degree of obsession.

Characterize the strength and types of connections between community members. It may turn out that the most effective activity in the fight against death is to increase the connectivity of the Longevity community.

We need to characterize the Longevity field itself, its structure, types of changes, and development dynamics.

I will write more about these and other categories. Perhaps 90% of the ideas won't find agreement with the reader.

But I can state from my experience that without a new language, a new picture of reality, metrics of social changes, and new categories, we will stagnate. We urgently need to create this.

Martin Borch Jensen (CSO at Gordian Bio) is looking for Scientific Chief if Staff:

“Work directly with me as our Scientific Chief of Staff & be part of everything it takes to run a growing biotech.

You'll have wide responsibilities, owning projects and culture improvements, organizing our teamwork, and helping me set the company strategy.

The ideal candidate combines scientific training (eg a PhD but degree not required) with excellent organization and communication, proactive problem solving, and handling a lot of balls at once.
Most of all you'd have good mind-meld with me, to absorb ideas and judgement fast.

Read more and apply here. And can learn more about GordianBio, including our mission and unique technology here.”

“I was always looking for ways to meaningfully improve people’s lives. For instance, I worked a lot with gifted children. At some point, I realized that no matter how well we do, in the end, frailty, disease, and death await everyone. Aging spares no one, be it businessmen, governors, farmers, it’s like an arch-problem.”

An interview with @MishaBatin, one of the co-founders of Open Longevity & Say Forever! movement.

LBF has published its plan to defeat aging:

https://www.longbiofellowship.org/roadmap

Vitalism Foundation is hosting The Longevity State Conference, a curated first-of-its-kind event focused on longevity states & how to hasten their emergence.

-50/50 workshops + talks
-longevity resort venue
-accommodation and food incl.

The number of spots is limited, and they are filling up quickly. Hurry up!