Computational Aging

We still know very little about human aging.

For example, how is my liver aging? How is my brain aging? I have no idea.

I am drawn to Prof. Michael Snyder's work on extreme measurement of his body. He has collected petabytes of data about his body physiology and genetics. This kind of data will help us measure aging-related interventions with more detail and personalization.

Prof. Snyder is also involved in the ENCODE project, which has the goal of "developing a comprehensive map of functional elements in the human genome" (Snyder et al, Nature, 2020). Many other large-scale (and small-scale) projects like these are in flight. Taken together, all this new data will give us a better systems-level understanding of biology and aging.

If we can know which genes are likely to contribute to aging, personalized for each individual's unique physiology and genes, then we can change our genes to extend our lives. In fact, we may already be doing this. Recently a volunteer in New Zealand had a cholesterol gene edited with CRISPR to a lower-risk version ("Edits to a cholesterol gene could stop the biggest killer on earth", MIT Technology Review, July 2022). This could be life-extending gene editing, here and now.

We are in the early days of systems biology. We are in the very early days of curing aging. Exponential curves can move quickly. We might be surprised what we can do in 20 years.

Are we making progress in life extension? Will it be in my lifetime?

Here's a signal that we're making real progress in life extension: when we have interventions that allow mice, rats, dogs and monkeys to live much longer and healthier than they currently do.

We're not there yet.

We've seen some incremental evidence of life extension in mice. Still, we can't get a mouse to live reliably to 5 years old and beyond. We can't get a rat to live much beyond 6 or 7, though maybe Harold Katcher's blood factors will change that?

Mice and rats are interesting, especially given the naked mole rat. Naked mole rats can live for 30+ years. They age much more slowly. They have better DNA repair. They get less cancer. They're similar to rats and mice (though more similar to guinea pigs, which live 5-7 years).

One interesting research path would be to make mice and rats (or guinea pigs) more like naked mole rats. Maybe gene editing or drugs to stimulate the same DNA repair pathways?

We also haven't seen much life extension yet in dogs and monkeys. The Dog Aging Project may change this soon. This study is giving rapamycin to older companion dogs.

Epigenetic reprogramming is promising and high-visibility. We'll know it's especially promising when we see mice, rats, dogs and monkeys living longer and healthier because of it. Same with the factors in young blood.

Put another way, if we can't reliably increase lifespan and healthspan in mice, rats, dog and monkeys, we probably not that close to achieving it in humans.

One of the most important questions within aging science is identifying good biomarkers of aging.

We need biomarkers that are predictive of aging rate and mortality. We have lots of biomarkers that are associated with aging rate and mortality, like cholesterol readings and epigenetic clocks. But we don't know how predictive they are.

We need these biomarkers to be more frequently measured than a full human lifespan. That way we can test interventions and see how they work. The more frequently these biomarkers can be taken (and still be predictive), the more we can make lots of personalized interventions (e.g. lifestyle, drugs, epigenetic reprogramming, gene editing).

Once we have these biomarkers, I could imagine a device like an Apple Watch giving us personalized recommendations based on population and personal data on how to slow our aging. Apple Watch captures large amounts of physiological and lifestyle data. They are increasing their data-capturing capabilities every year.

Working on biomarkers of aging is likely a very good use of time.