In August, 2023, AthenaDAO announced their commitment to combat ovarian aging, by dedicating $120,000 to Dr. Mario Cordero at Pablo de Olavide University. Not only was the preliminary science promising, but Dr. Cordero's own journey through fertility struggles, combined with his genuine desire to connect with the community he aimed to serve demonstrated a clear alignment in values. Since then, Dr. Cordero has been hard at work generating data, and we’re happy to let you know that things have gone well! 

In order to continue this important work, Dr. Cordero, together with AthenaDAO, is looking to the community for support in raising $75k to fund the next milestones. Before we look too far ahead, we thought we’d walk you through the most recent results. 

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Fertility 101

Fertility often influences major life decisions and future planning. Estimates suggest that one in six people experience fertility issues during their lifetime - a challenge that people usually bear privately behind closed doors, feeling isolated and confused. With no clear biomarkers to indicate how many eggs a woman has or how much time she has left to conceive, decisions about family planning can feel like a race against an invisible clock. This isn’t just about reproduction—it’s about choice. The ability to make informed decisions about when to start a family, or whether to start one at all, is crucial for many women. Even beyond fertility, ovarian aging also impacts the onset of menopause, a life-altering transition that many women may be unprepared for.

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What is Ovarian Aging?

Ovarian aging is the gradual decline of the processes that maintain fertility over time. As women age, their ovarian reserve—the number of viable eggs—naturally diminishes. But this decline isn’t the same for everyone. Some women experience a faster depletion, known as diminished ovarian reserve (DOR), where fertility declines earlier than expected. This can lead to fewer reproductive options for those affected.

At birth, women have around 1-2 million eggs, but by the time they reach menopause (around age 51), only about 1,000 remain. The most significant drop in egg quality and quantity occurs between the ages of 35 and 40, contributing to reduced fertility, a higher risk of miscarriage, and an increased chance of genetic issues in embryos. Globally, millions of women are affected by this decline, with many experiencing these challenges well before the average age due to conditions like DOR.

Factors that can cause ovarian aging to occur prematurely include genetics, autoimmune disorders, certain medical treatments (like chemotherapy), and environmental exposures. These influences can fast-track the decline, often leading to fertility challenges in women as early as their late 20s or early 30s.

Understanding ovarian aging is vital for women who want to take control of their fertility and make informed choices about their future. It’s also crucial for the doctors and specialists who support them in navigating these deeply personal decisions. By recognizing the signs early and raising awareness, we can help women explore their options sooner and find ways to preserve their fertility for when they’re ready.

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Tracking Ovarian Health

One key biomarker often used to track ovarian health is Anti-Müllerian Hormone (AMH), a hormone produced by cells in the ovary. As the ovarian reserves drop, so do the AMH levels, providing insights into how quickly time is catching up with a woman’s reproductive ability. But AMH isn’t the only clue! Another key hormone, Follicle-Stimulating Hormone (FSH), rises as the ovaries become less responsive to its signals, consequently, prompting the brain to pump out more FSH in an attempt to maintain fertility. This ultimately leads to a cycle of increasing FSH levels, indicating a declining ovarian reserve and reduced fertility, which results in fewer healthy follicles developing into viable eggs. In addition, these hormonal changes don’t happen in isolation. The ovaries themselves also undergo structural changes, leading to fewer healthy follicles developing into viable eggs. Together, these biomarkers form a roadmap of ovarian aging, one that researchers like Dr. Mario Cordero are actively working to understand, in an effort to uncover novel treatments. 

Until now, the process of ovarian aging has seemed like a predestined path, unable to be disrupted. However, what if there were ways to change direction? What if we could slow down this process? During research funded by the AthenaDAO community, Dr. Mario Cordero uncovered a surprising biological pathway, which may hold the key to new treatments. The pathway, known for its role in immune response, is called the cGAS-STING pathway.

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The Role of the cGAS-STING Pathway in Ovarian Aging

Emerging research shows that the cGAS-STING pathway might be a major cause of inflammation and tissue damage in aging ovaries. In both humans and animal models, higher levels of STING have been found in the ovaries, especially in a specific cell type called granulosa cells. These cells are crucial because they help eggs (oocytes) grow and mature, which is key to fertility. When this pathway is overactive in aging ovaries, it leads to increased production of certain inflammatory substances (such as IL-6 and Type I interferons). These substances cause inflammation and gradually reduce the ovaries' ability to function properly. When STING remains active for too long in ovarian cells, it can lead to several problems: the cells may age faster, their energy production can be disrupted, and their DNA can become damaged. 

All of these issues can speed up the loss of eggs and simultaneously lower the quality of the remaining ones.  

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Results from Dr. Cordero’s research so far

This research was designed to look at how the cGAS-STING pathway might be linked to aging in the ovaries and how it affects fertility. The researchers also studied how this process might be involved when chemotherapy damages the ovaries. The project was divided into three main parts, called work packages (WP).

WP1: Studying How the cGAS-STING Pathway Affects Aging in Ovaries

In the first part (WP1), the scientists looked at how the cGAS-STING pathway changes as women get older. The first experiments were designed to check whether or not cGAS-STING was involved at all with ovarian aging. If not, then it wouldn’t make sense to pursue further experiments. If yes, then full steam ahead!

They found that the STING protein is more active in older ovaries, which may contribute to the ovaries aging. This was seen in both human and mouse ovaries. They discovered that cells in the ovaries, especially in granulosa cells, are where this process happens most. Both mouse and human samples were tested because mice are often used as model organisms. However, if there was a big difference between the mouse and human data, then it would not be possible to continue using mice to study these effects, and another model organism would need to be chosen.

Since the data showed that mice can be used as a tool to study these effects, Dr. Cordero’s lab continued with their plan, and used a STING knockout model to see what would happen to the ovarian reserves if the STING protein was no longer present. Knockout mice are used to study what happens in an organism when a particular gene is absent. 

Dr. Cordero found that mice lacking the STING protein had more eggs and better fertility as they aged. The figure below shows mouse ovaries from ‘normal’ and ‘knockout’ mice, and the white arrows point to more follicles developing in the knockout mouse compared to the normal, wild-type mouse. 

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Finally, the researchers also found that women with diminished ovarian reserve had higher STING activity in their ovarian cells, as shown by higher levels of STING protein levels in samples from a healthy female compared to samples from a female with DOR. 

Together, the results from WP1 suggest that blocking the cGAS-STING pathway might help women keep their fertility longer as they get older. 

WP2: Looking at Chemotherapy’s Effect on Ovaries

In the second part (WP2), the researchers wanted to see if the cGAS-STING pathway also plays a role in how chemotherapy damages the ovaries. Early findings showed that chemotherapy increases STING activity in patients. 

In experiments with mice, they found that mice without the STING protein were protected from the harmful effects of chemotherapy on their ovaries. This means that blocking the cGAS-STING pathway could help protect women’s ovaries during chemotherapy, potentially saving their fertility while receiving life-saving treatment. 

WP3: Creating Therapies to Block the cGAS-STING Pathway

The third part (WP3) was about developing new drugs to block the cGAS-STING pathway. The scientists tested several small molecules and found one, called "A2," that works well at reducing the harmful effects of the cGAS-STING pathway, such as inflammation and cell death. This drug could be helpful in protecting or improving fertility in women as they age or undergo chemotherapy.

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It's time to fundraise for the next milestones!

True to the belief in equitable and accessible scientific research, AthenaDAO will be tokenizing the Cordero IP-NFT into Intellectual Property Tokens (IPTs) with the support of Molecule. These tokens enable the distribution of IP rights to holders to both raise funds for continued scientific research and empower the community to govern the resulting IP.

Due to the successful completion of the work packages in the first milestone of the project, Dr. Mario Cordero is looking to raise $75,000 USD to continue the work in milestone 2. With these funds, he is hoping to achieve two clear goals:

1. Continue the development of in vitro testing of these newly discovered inhibitors (A2) from WP3 
2. Test to see what happens when the cGAS-STING pathway is inhibited with Dr. Cordero’s newly developed compounds in animal models with reduced ovarian reserve

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Why choose the IPT model? 

By giving community members the power to co-develop research projects via IPTs, AthenaDAO is harnessing the potential of decentralized science. As the project moves forward, important decisions—such as which delivery vehicles to test, the best disease indications for clinical trials, and how to raise additional funds—will be guided by the collective expertise of the community. With the power of IP tokenization, the wisdom of the crowd will play a critical role in shaping the future of fertility research.

AthenaDAO will be sharing more details on the crowdsale soon - subscribe to their newsletter, join the community on telegram, or follow on X so you can be the first to know. 

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Supporting research that matters

At its core, this research is about empowering women with new options for their reproductive health. By tackling ovarian aging at a deeper level, we’re moving closer to a future where the limits of biology can be redefined. We’ve been honored to support Dr. Cordero’s partnership with AthenaDAO, and hope that you’ll join us on this journey. 

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References:

1. Jirge, P. (2016) ‘Poor ovarian reserve’, Journal of Human Reproductive Sciences, 9(2), p. 63. doi:10.4103/0974-1208.183514. 
2. Moolhuijsen, L.M. and Visser, J.A. (2020) ‘Anti-müllerian hormone and Ovarian Reserve: Update on assessing ovarian function’, The Journal of Clinical Endocrinology & Metabolism, 105(11), pp. 3361–3373. doi:10.1210/clinem/dgaa513. 
3. Oh, S.R., Choe, S.Y. and Cho, Y.J. (2019) ‘Clinical application of serum anti-Müllerian hormone in women’, Clinical and Experimental Reproductive Medicine, 46(2), pp. 50–59. doi:10.5653/cerm.2019.46.2.50. 
4. Decout, A. et al. (2021) ‘The CGAS–sting pathway as a therapeutic target in inflammatory diseases’, Nature Reviews Immunology, 21(9), pp. 548–569. doi:10.1038/s41577-021-00524-z. 
   

Life is the ultimate multiplayer game. We're all logged in, whether we choose to be or not. Some of us are grinding for XP, increasing the skill and resources of our character. Others are watching from the sidelines as our avatar slowly loses health. There is one universal truth for all of us in this game: it will end. 

Let's face it, death is the final boss. It's the game over screen nobody wants to see. But what if you could develop your own infinite health cheat code? What if we could keep playing the game indefinitely?

Enter the world of longevity research, where science can potentially unlock the secret to extended playtime  — a.k.a. lifespan.

The Longevity Trilemma

Finding this cheat code isn’t easy. If it were, we would have found it already. To change how our bodies interact with time, we need better potions (supplements), better gear (drugs), and better strategies (regimens). But like any cheat code, it’s only good if you know it actually works. When it comes to longevity, having proof-of-cheat-code is a must  — after all, we only have one “life” in this game. So how do we know what works?

Human trials? Too slow. Testing on mice? Still too slow. Consider this, there are more potential drug compounds than atoms in the universe! When it comes to longevity, you don’t want to settle for any option—you want the best.

These dynamics create a Longevity Trilemma, and longevity research must balance three key factors: 

1. Speed: We need results fast. Time is ticking. 
2. Cost: It can't break the wallet. We have to efficiently use resources to test the large chemical space.
3. Quality: The data must accurately predict how drug candidates will impact the lifespan of humans.

AI can help, but it needs lots of top-notch training data to propose potential life-extending treatments. So, how do we strike the perfect balance?

The Longevity Drug Testing Protocol 

Based on all available information, we believe a protocol to test new combinations to optimize human lifespan is as follows. 

Testing compounds in C. elegans (worms) → Daphnia Magna or Drosophila Melanogaster (fruit flies) → mice → rats → 1 human → 2 humans → n + 1 humans → broader public. This protocol ensures that data is generated on the least expensive organisms with the shortest lifespan before taking on more risk to cost and health.

If a regimen proves effective on C.elegans, further experiments can be run on flies or mice, with live data streamed to users. The goal is to eventually bring online testing on worms, and other organisms as well, letting the market decide which regimens and experiments should be performed among the menu of options.

Of course, regimens can enter at any point in the protocol (e.g. “mouse” instead of “C elegans”) based on the proposed mechanism of action and the financial and personal health risk profile of those funding or taking the regimen. 

Minimizing cost and health risk is what makes C elegans the ideal first experiment. 

Enter the Wormbot: The Unlikely Speedrunner

Meet Wormbot, our unlikely hero in our quest for immortality.

The Wormbot is a low-cost, rapid experimental platform developed by Ora Biomedical, founded by Matt Kaeberlein and Mitchell Lee to inexpensively test a large number of potential longevity regimens on C. elegans, a worm with a lifespan of 20 days. 

Why worms? Well, 40% of their proteins are similar to ours. They're like the tutorial level for human biology. Plus, they've shown an impressive correlation with how treatments affect mice's lifespans. It's not a 1:1 match for humans by any means, but it's a great starting point. The data from the chart below shows that compounds extending life in mice also extend life in the worms.

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Regimens are cultured with ~30 worms per well, monitored by a camera recording the worms’ movement and lifespan. This platform can be used to inexpensively test whether regimens may increase the lifespan in larger organisms (mice and humans). 

Pump.Science: Where Crypto Meets Immortality

This is where you come in. Pump.science is a platform that lets anyone submit longevity regimen ideas (drug strategies) to be tested on the Wormbot (and soon - other experiments), own the intellectual property (IP), and stream the results. It’s like gladiators in the Coliseum, if the Coliseum were a petri dish, the gladiators were microscopic worms, and their weapons were experimental longevity cocktails. Are you not entertained?

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Here's how it works:

1. Submit a regimen idea or back someone else's by buying tokens
2. Once the regimen reaches a certain market cap, the Wormbot experiment is run
3. Watch the experiment data stream as the regimen is tested on real worms
4. Buy tokens if you think the compounds can extend life and the regimen is valuable

The goal? Predict which treatments extend human lifespan. We're swapping financial yield (APY) for "time yield" – Percentage Life Extension (PLE). 

Gamifying the Longevity Game

Pump.science gamifies the Wormbot. The objective of the game is to predict whether a longevity regimen will increase lifespan in humans using the worm experiments as a signal. The higher the PLE, the greater the chance of winning. 

To play, users either submit a regimen for testing, which launches a new token, or fund others’ regimen ideas by purchasing their regimens’ tokens. 

To submit a regimen for testing, users can select from a list of available ones.

To buy tokens in an existing regimen, users can choose live tokens from the marketplace of all the regimens currently being tested. 

For each regimen’s market, users see a stream of the latest images taken by the Wormbot and some raw data (movement, growth) that can serve as leading indicators for whether the regimen is increasing lifespan. 

In other words, pump.science turns Wormbot into a tokenized prediction market for longevity regimens with a goal of increasing PLE in humans. 

Why is the platform called pump.science?

Pump.fun is a token launchpad on the Solana blockchain that launched in January 2024 and amassed well over 100 billion USD in volume in a period of months, and is now responsible for the greatest number of transactions on the Solana blockchain. The key innovation of pump.fun is enabling the creator economy for meme tokens, lowering the cost of creating a new coin to $2. 

Pump.science is built on top of pump.fun, so we called it pump.science. The key innovation of pump.science is enabling a creator economy for science tokens, starting with longevity regimens, by lowering the barrier to entry to fundraise and execute lifespan experiments while streaming the data for maximum transparency on the performance of each regimen. In other words, it’s pump.fun for science. 

We want to lower the friction to submitting, supporting, and justifying the products that will increase the duration of our lives.

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This kind of stadium science, scientific research with live, open-sourced data and real-time speculation, has not been sufficiently explored. Traditional biotech markets release data once experiments (typically clinical trials) are completed. Real-time data readouts in stadium science provide more opportunities for odds to change and enable continuous speculation by market participants. Participants can look at the data and make educated guesses on a continuous basis - either based on their a priori scientific understanding or by watching the experiment run. To propose a new regimen will likely require a deeper level of scientific understanding, but anyone can speculate on the regimen’s experiment. That means anyone can bet on the next longevity breakthrough on pump.science.

Why is this something people want? 

Finding ground truth data on longevity regimens is hard. Many advocates (marketers) for particular regimens have a financial interest in doing so. It is also commonly argued that longevity is a ‘problem for rich people,’ but time is the most valuable asset for all of us. We want to democratize not only the funding discovery of longevity breakthroughs but also their supporting evidence and products because those should be available to everyone. With pump.science, we hope to create a fair and open system for longevity and a new blueprint for science at large.

Come play with our worms. It’s the only game that isn’t wasting time - it’s creating it. 

Let's pump.science

Are you ready to pump.science? Visit the website, follow pump.science on X, or join the telegram.

Acknowledgements

Thank you to Krister Kauppi, Jesse Hudson, Hated by Fate, and Ora Biomedical for their inspiration and support.

DeSci Breaks Ground on Solana

Just like pump.fun is the poster child of Solana’s memecoin bull run, pump.science will be the poster child of Solana’s DeSci movement. 

Using bonding curves and a simple UX, pump.fun made launching meme coins (which used to be a somewhat mysterious process) simple, fast, fun, and transparent. Pump.fun showed that when the barriers to creation fall, more good ideas rise, and new users are drawn into crypto. It was proof that culture eats strategy for breakfast.
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We are no strangers to bonding curves. Molecule’s founder was yapping about bonding curves funding science back in 2019. Molecule’s newest product, Catalyst, leverages a unique bonding curve for funding early-stage scientific research with IP tokens. But Catalyst is on Ethereum (Base). Solana is faster. And scientific progress must accelerate. 

Pump.science: Betting on How to Live Forever 

With the Solana Foundation grant, Molecule is developing pump.science, a platform for funding and streaming longevity experiments powered by Wormbot.

On pump.science, anyone can submit or fund experiments with drug regimens for C. elegans worms trying to extend their 20-day lifespan. Every experiment gets a token named after the drug regimen and seeks to answer the question, “Does this regimen extend the worm's lifespan?” 

Anyone can buy the drug regimen’s tokens, watch the experiments unfold on Wormbot, and, if the regimen extends the worm’ lifespan, have a stake in the resulting drug development and distribution. The goal? Bet on the winning regimen, get it to humans, and live forever. 

This isn’t just fun. It's science.

Learn more about pump.science by joining our Telegram and following us on Twitter.

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About Molecule

Molecule is dedicated to advancing scientific research through democratized funding and the tokenization of intellectual property (IP). By transforming IP into liquid, onchain assets, Molecule aligns the incentives of researchers and funders, fostering a more collaborative and efficient research ecosystem.

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