I eat a lot of plants and try to avoid eating other mammals, even though they do taste good. If I work out, I will eat meat. • I don't smoke. I try t… - David A. Sinclair

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.

That's what people have been doing for centuries — without even knowing it — in centenarian-heavy places such as Okinawa, Japan; Nicoya, Costa Rica; and Sardinia, Italy. These are, you might recognize, some of the places the writer Dan Buettner introduced to the world as so-called Blue Zones starting in the mid-2000s. Since that time, the primary focus for those seeking to apply lessons from these and other longevity hot spots has been on what Blue Zone residents eat. Ultimately this resulted in the distillation of "longevity diets" that are based on the commonalities in the foods eaten in places where there are lots of centenarians. And overwhelmingly that advice comes down to eating more vegetables, legumes, and whole grains, while consuming less meat, dairy products, and sugar.

We can't prevent all DNA damage — and we wouldn't want to because it's essential for the function of the immune system and even for consolidating our memories57 — but we do want to prevent extra damage. And there's a lot of extra damage to be had out there. Cigarettes, for starters. There aren't many legal vices out there that are worse for your epigenome than the deadly concoction of thousands of chemicals smokers put into their bodies every day. There's a reason why smokers seem to age faster: they do age faster. The DNA damage that results from smoking keeps the DNA repair crews working overtime, and likely the result is the epigenetic instability that causes aging. And although I'm not likely to be the first person you'll hear this from, it nonetheless bears repeating: smoking is not a private, victimless activity. The levels of DNA-damaging aromatic amines in cigarette smoke are about fifty to sixty times as high in secondhand as in firsthand smoke.58 If you do smoke, it is worth trying to quit.