Lifespan

Lifespan boils down a bunch of the longevity research that David Sinclair has done throughout his career studying age.

After reading it, my current take is one of mixed skepticism. Sinclair's research seems sound, as does his findings in yeast and mice, and his arguments make logical sense. That said, I'm unsure of the various supplements which he recommends. The human body is such a complex system that it seems difficult to know which systems will react poorly to extra stimuli or not.

That said, the book did tell me a lot about how DNA and genomic systems work. Reading it made me much more optimistic that we'll find systems to significantly fight aging in the next 50-100 years.

Gene A and Gene B

Imagine the world tens of millions of years ago... as unstable primordial ooze. There's lots of little molecules that are floating around in this ooze each one occasionally linking with other molecules to create bigger, macro-molecules.

Eventually one of these macro-molecules forms a replicator, it starts creating many little copies of itself from the resources available! Sinclair calls this replicator Gene A.

Gene A continues to pump out more copies of Gene A... and everything goes well until... it doesn't. Suddenly there's a mutation in Gene A, or a shortage of resources, or some other key mechanism. Whatever the reasons, the environment has changed so that Gene A should actually stop reproducing for a minute.

That's where Gene B enters the picture. Gene B is the regulator and repair gene for Gene A. It helps tell Gene A when times are tough and when to stop reproducing, as well as help.

Though it's a simplified view, Sinclair argues that our body still works in this way... via DNA and Epigenome.

DNA as digital information, epigenome as analog

We were all taught that DNA is the building block for genes, it's the information that encodes every single cell in your body.

But each cell gets the same complete copy of your DNA... how can cells vary? Why do cells have specialized functions, like your liver vs your brain vs a blood cell if they all have the same DNA?

That's where your epigenome comes in. It's the set of proteins and enzymes inside your body that respond to your environment that regulate which genes are expressed and how cells form.

Sinclair thinks of DNA as a digital signal (it can't encode much, other than AGCT) while your epigenome is an analog signal. It can express many more genes just as a function of which proteins are active inside your system.

Aging as a disease caused by information degradation

The two above pieces tie into the author's core thesis; that aging is actually caused by mutations and degradations in DNA which cannot be repaired.

At some point, your body has too many breaks which begin to replicate–and it is this set of bad replications which cause humans to age. In effect, we have issues with our Gene A, and we need Gene B to repair it!

Sinclair has been studying a set of proteins called Sirtuins, which he claims act like Gene B. They regulate and repair our DNA so that it doesn't reproduce mutations.

Aging is a treatable disease

Sinclair then argues that aging itself is caused by a lack of these Sirtuins. As the body ages, more and more DNA mutations begin to occur. When Sirtuins can no longer both repair the DNA and reproduce themselves at an appropriate rate, that's when problems happen.

Sinclair thinks that aging is actually a treatable disease, by simply increasing the DNA repair mechanisms in the body. He believes that increasing Sirtuin levels and precursors can allow us to prolong human life, and potentially, reverse aging.