Adding 30 years of healthy lifespan as quickly as possible

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.

Exciting paths forward in longevity science

Longevity science seems to be experiencing rapid progress, yet expected lifespan is still <100 years even if you do all the right things (diet, exercise, sleep, don't smoke, etc).

We need a lot more progress.

Here are six paths I'm excited about:

  1. The translation of discoveries in the last 30 years into actual medicines, such as senolytics, metformin, rapamycin, leveraging "young" blood and microbiota, etc
  2. Cellular rejuvenation using Yamanaka factors
  3. Cellular rejuvenation beyond Yamanaka factors, e.g. Sengstack et al (2022, BioRxiv)
  4. A better understanding of why our cells and tissues age
  5. Massive multi-modal 'omics and imaging data applied to aging
  6. Reformulating aging biology wet lab experiments as computational/AI models, e.g. language models for cellular aging

These paths each have the potential to guide us to more healthy years.

The fastest path to biomedical breakthroughs: Continuous measurement of personal aging and health

One of the biggest challenges with slowing aging and improving health is that we don't closely measure how we age. Most people do annual blood tests, look for changes in how they look in the mirror, and wait until they get a specific disease. This is like taking basic measurements once a year or even less. It means our understanding of health and aging is very limited. We can't quickly try new things and see if they work. New therapies are beholden to the pace of slow, expensive clinical trials that take decades to bring new therapies to market. At this pace, we will have to get lucky to cure aging. In short, today's healthcare system leads to slow, incremental, analog improvements. 

Instead, we should track our complete health real-time. We should have real-time, continuous, zero-marginal-cost data on the health of every tissue and system, our rate of molecular damage throughout our bodies, and frequent predictions on our mounting health risks. It would provide tremendous understanding of aging and health. Then, we would apply modern ML tools to this data across lots of people with lots of health outcomes over time. These ML tools would be able to model our health, predict our health risks, and suggest interventions to improve our health. It's hard to overstate what this will bring.

Imagine a Chat-GPT for our own personal health. Let's call it Doc-GPT. Doc-GPT would be trained on data from hundreds of millions of people over many years. It will comb your data looking for risks and making suggestions. You will get reminders and suggestions frequently based on your risks and behavior. It will become your primary preventative physician.

I believe we are trending to this world. We will have automatic, continuous measurement of aging and health. Two big trends are making this possible: 1) the explosion of health data tracked on our phones and wearables, and 2) the exponential decrease in the cost of 'omics measurements. My iPhone and Apple Watch already have the data to make much better sense of my health than any doctor. They know my heart rate, gait, voice, daily activities, and much more. Our heart rate variability, voice, and gait each provide windows into our health and molecular damage. They have my photo library from the last 10 years, and faces provide a good window into our overall health [1]. They know how social and active we are, and how much we exercise. They know when people have heart attacks. They know when we go to the hospital. They can sense dementia. They probably know when we die. Apple has over 1 billion iPhone users and 100 million Watch users. They can see what increases or slows our aging. They can see what helps and hurts our health.

Our wearables and phones don't yet directly know the molecular damage in our cells and DNA. This is fundamental data to aging and health. Fortunately, 'omics measurement tools are riding an exponential curve trending towards essentially zero cost. ~20 years ago it cost billions of dollars to map the human genome. Today, we can do it for around $100. This is trending towards zero. As it does, we will know the status our DNA, epigenetics, RNA, and proteins much more frequently. It's hard to imagine having this data in real-time, but we are trending in that direction.

This health data from phones, wearables, and omics is absolutely massive. It's on the scale to build the Doc-GPT of the future. Apple, for example, may already be able to build a Doc-GPT with the data they have that is better than any doctor today. These data may replace much of what clinical trials do. These tools are coming, and they can't come soon enough. The race is on.


References:

[1] Xia X, Chen X, Wu G, Li F, Wang Y, Chen Y, Chen M, Wang X, Chen W, Xian B, Chen W, Cao Y, Xu C, Gong W, Chen G, Cai D, Wei W, Yan Y, Liu K, Qiao N, Zhao X, Jia J, Wang W, Kennedy BK, Zhang K, Cannistraci CV, Zhou Y, Han JJ. Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle. Nat Metab. 2020 Sep;2(9):946-957. doi: 10.1038/s42255-020-00270-x. Epub 2020 Sep 7. PMID: 32895578.