AlphaFold and The Fiscal Importance of Understanding Why We Age

"Where do I think the next amazing revolution is going to come? And this is going to be flat-out one of the biggest ones ever. There's no question that digital biology is going to be it." — Jensen Huang, founder & CEO of NVIDIA, Dec 6, 2023

A Macro Investor’s Journey into Health and Longevity

As a macro investor, healthcare was rarely on my radar beyond its defensive sector characteristics, similar to utilities or consumer staples. While biotech occasionally sparked interest, it remained too speculative without deep expertise. As a health-conscious person who loves life and being healthy, I have always been focused on longevity. You can learn a lot about me by looking at the Twitter thematic lists I have set up for research. Unsurprisingly, based on my Substack content, these lists are dominated by AI, Bitcoin, and economics. Also included is a list on longevity—a theme that I spend more time on than any other.

My interest in longevity and healthspan increased significantly about a decade ago after a visit to Singularity University, an innovation incubator focused on exponential technologies addressing global challenges. A presentation there forecasted a future where technology and health would converge, accelerating us toward what Ray Kurzweil, one of the founders, calls "Longevity Escape Velocity"—the point where technological advancement adds more years to our remaining lifespan than time passing. Simply put, for each calendar year, life expectancy would increase by more than one year. This inspired me to do daily research, eventually leading to an anti-aging approach I regularly mentioned on my podcast, In Search of Green Marbles. It also led to ongoing rabbit-hole research on when we might approach Longevity Escape Velocity.

Over the last five years, advancements in fields like CRISPR and mRNA technology, along with Moderna’s AI-based approach to rapidly developing the COVID-19 vaccine, have shown that technology’s impact on lifespan and healthspan is accelerating. In the last two years, nothing has brought more media attention to healthcare than Ozempic. Just in the past month, reports indicated that obesity rates in the U.S. are finally declining. This trend toward improving healthspan and lifespan was further reinforced when the Nobel Prize in Chemistry was recently awarded to two members of Google DeepMind for their work on AlphaFold. Additionally, AlphaFold was named one of Time’s best inventions for 2024.

DeepMind captured AlphaFold's significance well in 2020: “Proteins are the building blocks of life, they underpin every biological process in every living thing. And, because a protein’s shape is closely linked with its function, knowing a protein’s structure unlocks a greater understanding of what it does and how it works.” Nobel Laureate and Royal Society President Professor Venki Ramakrishnan echoed this, calling AlphaFold’s achievements a “stunning advance” on the 50-year-old protein-folding problem in biology, with implications that will “fundamentally change biological research.”

This year, DeepMind announced the next phase with AlphaFold 3, which aims to “transform our understanding of the biological world and drug discovery.” Building on AlphaFold 2’s breakthrough in protein structure prediction, AlphaFold 3 expands beyond proteins to a broad spectrum of biomolecules, opening doors to discoveries in malaria vaccines, cancer treatments, enzyme design, biorenewable materials, resilient crops, and accelerated genomics research. AlphaFold has been cited over 20,000 times. So far, over 500,000 researchers from 190 countries have used the AlphaFold database to explore more than 2 million structures. It has been recognized for its profound scientific impact, receiving accolades like the Breakthrough Prize in Life Sciences.

AlphaFold has unlocked new pathways to understanding the cellular foundations of aging. By accurately predicting protein structures, AlphaFold enables researchers to investigate the molecular drivers of aging and age-related diseases, potentially leading to treatments that slow or even prevent these conditions.

This comes at a critical time. In 2022, health spending reached $4.5 trillion, with Medicare and Medicaid combined making up 39% of total health spending and health insurance 29%. Consider the enormous waste in this system: I spent four hours on the phone with United Healthcare in a single day last week. The U.S. budget deficit is at alarming levels and is projected to worsen in the coming years. An aging population poses a significant economic burden. With federal programs like Medicare and Medicaid already consuming about 25% of the U.S. federal budget, the financial strain of age-related diseases is set to grow as populations live longer but not necessarily healthier lives. Understanding and addressing the root causes of aging could help reduce this strain by shifting healthcare from reactive treatment of chronic diseases to preventative care that extends healthspan—the period of life spent in good health.

AlphaFold – A Game Changer in Protein Structure Prediction

Proteins are essential to nearly every function within the body, and understanding their structures is crucial for addressing age-related diseases. AlphaFold’s breakthrough ability to predict protein structures provides researchers with critical insights into cellular processes, helping to reveal how specific molecular mechanisms drive aging. This advancement significantly reduces the time and costs associated with protein structure determination, accelerating the pace of drug discovery.

Beyond individual diseases, AlphaFold’s mapping of protein structures enables scientists to address aging’s underlying mechanisms, opening up the possibility for breakthroughs in longevity therapeutics. These therapies aim to target multiple age-related conditions by addressing common biological pathways. Research in longevity therapeutics has already shown promising results, with studies suggesting that treatments targeting aging itself—rather than isolated diseases—could improve health outcomes and reduce healthcare costs associated with multimorbidity, or the simultaneous presence of multiple chronic diseases.

The Convergence of AI, Biology, and Longevity Therapeutics

AlphaFold’s success highlights a trend of convergence in AI, where insights from genomics, pharmacology, and diagnostics come together to address the complex nature of aging. This convergence enables the development of therapies that treat aging as a holistic condition rather than as a collection of isolated symptoms.

1. Understanding the Cellular Hallmarks of Aging: Aging is driven by interconnected cellular processes such as genomic instability, mitochondrial dysfunction, and chronic inflammation. Researchers like Carlos López-Otín have categorized these processes into primary, antagonistic, and integrative hallmarks of aging. By mapping protein structures, AlphaFold provides a foundation for understanding how these hallmarks interact, offering a clearer view of the aging process and paving the way for therapies that target multiple pathways simultaneously.

2. Development of Longevity Therapeutics: Advances in AI-driven pharmacology are enabling the development of drugs that treat multiple chronic diseases by targeting shared biological pathways. For example, GLP-1 drugs, initially developed for metabolic conditions, have shown efficacy in improving cardiac and renal health. Similarly, longevity therapeutics aim to extend healthspan by addressing aging’s root causes, potentially reducing the prevalence of multimorbidity and alleviating the strain on healthcare systems. In 2021, Google unveiled a new company under their umbrella called Isomorphic Labs to use AI to reimagine “the entire drug discovery process.” Ninety percent of drugs fail in trials, and the average time from beginning to end is 10-15 years—highlighting further waste in the healthcare system. Earlier this year, Isomorphic Labs announced collaborations with Novartis and Eli Lilly.

3. Epigenetic Reprogramming and Gene Therapy: Emerging technologies in gene therapy and epigenetic reprogramming, explored by companies like Rejuvenate Bio and Tune Therapeutics, hold promise in reversing aspects of biological aging. By targeting gene expression profiles associated with aging, these therapies could restore cellular function, potentially delaying or reversing age-related decline. This approach not only improves individual health outcomes but also reduces the economic burden of age-related diseases.

Economic Implications of Extending Healthy Lifespan

The economic impact of extending healthspan is substantial. At the ARDD conference in 2023, Michael Ringel, a partner at Boston Consulting Group, presented analyses on the potential economic gains from healthspan extension, drawing on studies from three groups:

• Murphy and Topel (University of Chicago): Murphy and Topel analyzed the economic value of increased healthspan and lifespan from 1970 to 2000, estimating an annual economic boost of $3 trillion. This figure underscores the significant benefits that even modest improvements in healthspan can yield.

• Dana Goldman and Colleagues: Goldman and his team projected the economic impact of a slight increase in healthspan, starting at age 50 and gradually extending. This modest change was estimated to add over $7 trillion in value, demonstrating the economic potential of gradual improvements in older adults’ health.

• Scott, Ellison, and Sinclair: In their paper "The Economic Value of Targeting Aging," Andrew Scott, Martin Ellison, and David Sinclair analyzed the economic benefits of targeting aging itself rather than focusing on individual diseases. Their findings suggest that a slowdown in aging, resulting in a one-year increase in life expectancy, would yield economic gains of $38 trillion. A ten-year increase in life expectancy due to improved aging processes could have an economic impact of $367 trillion globally. Their research highlights that compressing morbidity—focusing on making lives healthier rather than just longer—provides greater economic value and that targeting aging itself has the potential for far larger economic gains than eradicating individual diseases.

These studies show that improving healthspan is not just beneficial for individuals but holds immense value for economies. By reducing the prevalence of chronic diseases and extending the period of life spent in good health, longevity therapeutics could ease fiscal pressures associated with aging populations, such as the rising costs of Medicare and Medicaid. As more people remain healthy for longer, governments could redirect funds from reactive healthcare to other areas, supporting economic growth and innovation.

The Path Forward – A Holistic Approach to Aging and Economic Stability

As society advances toward longevity therapeutics, we are not just improving individual health outcomes but potentially transforming economic stability. The convergence of AI, genomics, and epigenetics offers the possibility of compressing morbidity, allowing individuals to live longer with fewer years spent in poor health. This compression could dramatically reduce the costs associated with age-related diseases, enabling a sustainable healthcare model that eases the strain on public resources.

Healthier aging could also impact workforce dynamics. As people remain physically and mentally capable for longer, they may extend their careers, contributing to productivity and reducing the economic dependency ratio. Consider the disruption that Ozempic has already created in consumer spending on processed foods, sugar, and alcohol. Another wave of disruption may come as people embrace healthier lifestyles.

Extended working lives would generate more tax revenue, reducing the need for increased public spending on social support systems. Additionally, healthier elderly populations could contribute to communities and mentorship roles, enhancing social structures and reducing overall care costs.

AlphaFold’s groundbreaking contributions, honored by the Nobel Prize, mark a pivotal moment in our understanding of biology, aging, and the economy. As a macro investor, I now view healthcare not as a defensive sector but as a cornerstone of economic stability and growth, as well as a major disruptor of consumer and government spending. Since 2020, the top-performing companies in the S&P 500 with market caps over $500 billion illustrate this shift. AI-driven Nvidia ranks first, and, perhaps surprisingly, Eli Lilly comes in second. Healthcare is a significant expenditure for consumers, with most spending directed to doctors and hospitals. If consumers can instead invest in maintaining health and slowing aging to remain more active, these resources could be redirected to fuel other sectors of the economy.

The work of researchers like Murphy, Topel, Goldman, Scott, Ellison, and Sinclair underscores the profound economic benefits of extending healthspan, demonstrating that longer, healthier lives are not just an aspiration but a fiscal imperative. Through AI convergence, we stand on the brink of a new era where aging populations contribute to economies rather than drain them, driving growth, innovation, and stability. AlphaFold and the Nobel Prize-winning team at DeepMind offer a path to a future where extended healthspan not only enhances lives but also redefines the economic foundations of aging.

Now, go eat healthy, do some yoga and deep breathing, and get a good Oura ring sleep score while we wait to hit Longevity Escape Velocity!