What Are Sirtuins — and Why Are They Called Your Longevity Genes?

If there's one family of proteins at the absolute heart of modern longevity science, it's the sirtuins. Discovered in yeast cells in the 1990s — partly through David Sinclair's own early research — sirtuins have since been found in virtually every organism on Earth, from bacteria to humans.

Understanding what they do, and why they lose effectiveness as we age, is central to understanding how to slow down the ageing process.

Sirtuins are the conductors of your cellular orchestra

Your cells contain roughly 20,000 genes. At any given moment, only a subset of these genes should be active — and which ones are active determines what type of cell you are and how well it functions. Sirtuins are among the key proteins responsible for maintaining this gene expression — turning the right genes on, keeping others off, and preserving the cellular identity that keeps your body working correctly.

Think of them as conductors of an orchestra. The musicians (genes) are all present. But without the conductor ensuring everyone plays the right notes at the right time, the result is noise, not music.

Sirtuins also repair DNA — but at a cost

Sirtuins have a second crucial job: repairing broken DNA. Every day, an estimated 20 trillion DNA breaks occur in your body's cells — from radiation, stress, normal metabolic activity, and environmental toxins. Sirtuins are first responders, rushing to sites of DNA damage to help orchestrate repair.

But here's the problem. When sirtuins rush to repair a DNA break, they leave their normal post — the genes they're supposed to be regulating. While they're away fixing the emergency, those genes drift. Some that should be on turn off. Some that should be off switch on. And when the sirtuins return, they don't always go back to exactly where they started.

Repeat this process over trillions of cells, millions of times, over decades — and the cumulative effect is what we experience as ageing.

NAD+ is the fuel sirtuins need to work

Critically, sirtuins can't do either of their jobs without NAD+. It's the catalytic fuel that powers their enzymatic activity. Without adequate NAD+, sirtuins become sluggish and ineffective. And since NAD+ levels fall by up to 50% between the ages of 40 and 60, this is a significant problem.

Raising NAD+ levels — through fasting, exercise, and NAD+ precursor supplements — is one of the most direct ways to restore sirtuin activity and, by extension, help your cells maintain their identity and repair their DNA more effectively.