Computational Aging

Goals for 2033

1. Look, feel, move, and do activities like I’m closer to 40. In other words, I have dramatically slowed my rate of aging.
2. I know and monitor in near real-time my risk for general aging and each major disease. I know how to balance lifestyle and pharmaceuticals to keep this risk low, with close to real-time updates. As a result of this monitoring and intervention, my risk is very low.
3. I take the first of various FDA-approved therapies to slow and reverse aging for various organs/systems. Eventually there will likely be therapies for muscle, bone, brain, heart, blood, liver, skin, etc.
4. Most people around the world can will be able to do this within another 5-10 years because these technologies are safe, approved by regulatory agencies, accessible, and affordable. 

What do we need to make this a reality?

1. Data-driven real-time monitoring of aging and disease risk
2. Data-driven, personalized real-time interventions to reduce this risk
3. FDA approved therapies for cellular rejuvenation across various tissues
4. Improved fundamental understanding of aging biology

What is the current situation?

• Fundamental understanding of aging biology is rapidly improving. There are probably 100,000s of researchers working on this around the world from various angles. Trends and demographics suggest this will be millions of researchers soon.
• Rapid AI progress + data growth are making data-driven monitoring and intervention in aging much more feasible. Aging science can ride these two exponential curves.
• It is still unclear how much lifestyle changes + known drugs/therapies can slow aging. That said, if I had to guess, known technologies could make average lifespan more like 100-110 if they were rigorously applied with personalized measurement and interventions. But, they will not “rejuvenate” our bodies, or at least not that much.
• FDA approval of rejuvenating therapies is a big question mark. Early clinical trials are started and on their way. The first approvals will really speed this up. We need fast progress here!
• New drugs are typically very expensive. For anti-aging drugs, there will be a strong incentive for governments to subsidize these drugs to reduce the cost burden of age-related disease. Hopefully this will help adoption and affordability.

I posted my first research paper with Abbasi Lab and a great team of collaborators: "Unsupervised pattern discovery in spatial gene expression atlas reveals mouse brain regions beyond established ontology."

Here's the link: https://www.biorxiv.org/content/10.1101/2023.03.10.531984v1.full.pdf)

In this manuscript, we show that unsupervised machine learning (ML) can rapidly create maps of the brain based purely on 3D gene expression data. We demonstrate this in the adult mouse brain that goes beyond established ontology. Existing maps are typically hand-drawn, and can take years of person-hours to complete. By contrast, this method (osNMF) can run in a few hours on a MacBook Pro and is potentially less biased. It is applicable to any tissue or organism. Tissue maps are important. They help us understand function, development, disease, and aging.

This new method is just one of the countless examples of the powerful combination of ML + new data generation methods. Together, they are increasing the pace of biological discovery. Ours was a relatively basic ML approach––and it leads to orders of magnitude improvement in generating tissue maps. This improvements are happening all over the place.

More healthy years is one of the greatest possible gifts.

We have doubled average human life expectancy in the last 150 years. Much of this came from reducing child mortality, as can be seen in the compression of the red/orange/yellow lines in the figure. Excitingly, in the last 50 or so years, we are starting to see gains in older age. The life expectancy for a 70 year old in 1850 England and Wales was around 79 years, which means a 70 year old could expect to live for 9 more years. In 1950, this number hadn't really budged. The tools that improved child mortality (e.g. antibiotics, vaccines, etc) don't help as much for the diseases of old age (e.g. heart disease, cancer, dementia, etc).

Today, with the growing population of older people, the medical system and drug discovery are far more focused on diseases of aging. The life expectancy for a 70 year old in England and Wales today is 86 years. That means we've added ~7 years in 70 years. That's still slow progress (e.g. 1 year gained every decade). It's not enough to help you or me live much longer.

However, you can see that the curve of improvement for older people seems to be showing exponential improvement (I took the liberty of adding the red arrow to emphasize this). Might we be seeing exponential improvement? What could keep this curve exponential? How can we add 30 years of life expectancy for the typical 70 year old in the next few decades? That would be a rate of improvement closer to 1 extra year annually. People have called this "longevity escape velocity", where lifespan/healthspan is growing faster than we can age.

Here's a general framework for how to think about adding 30 healthy years broadly to people around the world

Horizon 1 improvements: Horizon 1 is where we use known science to help people live longer. For example, it appears that the average person could add ~10-15 extra healthy years based purely on lifestyle. This could be as simple as regular exercise (like 30-60 minutes per day, even including brisk walking plus some higher intensity workouts and regular weight training) and a Mediterranean diet. Exercise and diet are amazing because they appear to slow the progression and risk of the scariest diseases, including dementia, cancer, diabetes, and heart disease. Already this is a big industry, but I expect dozens of new $ billion companies to get created simply helping people apply known science to their lives. I also expect the biggest consumer internet companies in the world (Apple, Google, Amazon, etc) to deliver exciting new solutions. Entrepreneurs, go forth! 

Horizon 2 improvements: Horizon 2 is where we apply the learnings in aging biology from the last 30 years to develop new therapies and drugs. These include promising drugs like Metformin and Rapamycin that work well in model organisms and human biomarkers, but haven't been thoroughly tested in humans yet for lifespan extension. They include promising lifestyle interventions like intermittent fasting. They include a crop of new drugs, like BioAge's new sarcopenia (muscle loss) drug that is heading for Phase 2 clinical trials. It also includes the disease-specific progress, such as in Alzheimer's (finally) and cancer. Imagine 5-10 new drug approvals and 1-2 new lifestyle interventions over the next 20 years. If they work on relatively distinct pathways or pathologies, we might get another 10-20 years from these. Maybe everyone over 40 or 50 will be taking a few anti-aging drugs by 2040, e.g. statins for aging? Drug developers, go forth!

Horizon 3 improvements: Horizon 3 are the big, paradigm-changing, rejuvenation technologies. For example, cellular rejuvenation via Yamanaka factors is one of these. They have the potential to rejuvenate our cells and tissues. Horizon 3 improvements are harder to work on. They're risky and uncertain. They may not pay as well. They may fail outright. And sometimes these emerge in surprising ways or places, like Yamanaka factors did. There is tremendous investment going into cellular reprogramming including Yamanaka and other factors. We will learn a lot there. There are other high-risk Horizon 3 possibilities out there too, often in the realm of basic science. It could include replacement organs or tissues grown in a lab. It could include regular blood replacement based on the learnings of parabiosis. It could include riding the exponential improvements in AI to a profound understanding of aging biology. We need people to pursue these. Dreamers and inventors, go forth!

It's hard not to feel optimistic about the future of human longevity. There is tremendous pressure to innovate from our aging population and the growing cost of healthcare. There is a deep human desire to feel and be youthful. Older people, who hold most of the world's wealth, will invest much of it towards health and longevity. Horizon 1 and Horizon 2 have great, growing momentum. They alone may deliver 30 more years of healthy life. Horizon 3 has momentum, but I believe we need more people and money exploring Horizon 3 ideas. A single Horizon 3 technology may bring billions of people decades of more healthy years.