Youth → broken DNA → genome instability → disruption of DNA packaging and gene regulation (the epigenome) → loss of cell identity → cellular senescen… - David A. Sinclair

The longevity genes I work on are called "sirtuins," named after the yeast SIR2 gene, the first one to be discovered. There are seven sirtuins in mammals, SIRT1 to SIRT7, and they are made by almost every cell in the body. When I started my research, sirtuins were barely on the scientific radar. Now this family of genes is at the forefront of medical research and drug development. Descended from gene B in M. superstes, sirtuins are enzymes that remove acetyl tags from histones and other proteins and, by doing so, change the packaging of the DNA, turning genes off and on when needed. These critical epigenetic regulators sit at the very top of cellular control systems, controlling our reproduction and our DNA repair. After a few billion years of advancement since the days of yeast, they have evolved to control our health, our fitness, and our very survival. They have also evolved to require a molecule called nicotinamide adenine dinucleotide, or NAD. As we will see later, the loss of NAD as we age, and the resulting decline in sirtuin activity, is thought to be a primary reason our bodies develop diseases when we are old but not when we are young.

In animal studies, the key to engaging the sirtuin program appears to be keeping things on the razor's edge through calorie restriction — just enough food to function in healthy ways and no more. This makes sense. It engages the survival circuit, telling longevity genes to do what they have been doing since primordial times: boost cellular defenses, keep organisms alive during times of adversity, ward off disease and deterioration, minimize epigenetic change, and slow down aging.

DELETING THE ZOMBIE SENESCENT CELLS IN OLD TISSUES. Thanks to the primordial survival circuit we've inherited from our ancestors, our cells eventually lose their identities and cease to divide, in some cases sitting in our tissues for decades. Zombie cells secrete factors that accelerate cancer, inflammation, and help turn other cells into zombies. Senescent cells are hard to reverse aging in, so the best thing to do is to kill them off. Drugs called senolytics are in development to do just that, and they could rapidly rejuvenate us.