Living to 150

Friends,

Let me ask you a question.

If we cured all cancers, by how much would we extend the average American’s lifespan?

Answer: 3 years (Science, 1990).

In fact, research into centenarians (individuals who have lived to 100+) shows that they get all the same problems the rest of us get (cancer, heart disease etc), just a bit later on in their lives. It seems they have an extended period of ‘good health’ before the inevitable.

So how can we, like Methuselah, live to 969? Or more realistically — how does one live to 150?

Prof David Sinclair prefaces Lifespan: Why We Age—And Why We Don’t Have To with the following (roughly):

99% of living longer, your mother could have told you. Do your best to avoid the big four (diabetes, heart disease, Alzheimer’s and cancer). Basically — don’t eat sh*t, don’t get fat, exercise and don’t smoke.

But this isn’t very exciting. With good genetics, maybe it could get you to 90 — but what about 150?

First principles thinking is very in vogue at the moment. I even titled a podcast after it. It means solving a problem by first understanding the very basics of what’s going on. Elon Musk uses it to send rockets into space.

To ‘solve’ ageing with the first principles approach, you’d start by learning about the nine hallmarks of ageing.

Then you might create therapeutics which delay some of these cellular processes.

But consider a much sexier alternative: The Throw Sh*t at the Wall and See What Sticks Approach (TSWSWS).

Another approach is not to understand, but just see what works.

Sounds kind of un-scientific, but consider that after a century of use — we still don’t understand how paracetamol works. But RCTs show that it is both safe and efficacious. So we use it anyway 🤷‍♂️

Here’s the most exciting anti-ageing drug being studied with the TSWSWS approach. And it only costs 10 pennies.

There are something like seven groups of anti-diabetic drugs.

With 4 million diabetics in the UK, researchers became interested in what the most efficacious anti-diabetic regime was. Which anti-diabetic drug led to the longest lifespan?

Curiously, diabetics treated with metformin (green line) lived longer than similar people who didn’t have diabetes (black line).

Someone with a (significant) disease lives longer than someone without the disease. That’s crazy.

Does this make metformin a longevity drug? Could we give it to completely healthy, non-diabetic people — and increase their lifespan?

Maybe.

The TAME and MILES trials are looking at giving non-diabetic older adults metformin. It could be targeting all nine processes of ageing from the ground up, but in true TSWSWS spirit — no one really knows.

I suspect that in the future, metformin will be used much like a statin. More interestingly, what would happen if we gave 20-year olds metformin. Would they live to 150?

🦹🏽‍♂️ After outline.com stopped working, I found printfriendly.com which is a nice way to get past newspaper paywalls.

😈 This plugin adds a free sci-hub link to academic papers.

🚗 This was cool. To see a $30M fund use Fast&Furious branding.

With warmest wishes,

Musty