When sirtuins shift from their typical priorities to engage in DNA repair, their epigenetic function at home ends for a bit. Then, when the damage is… - David A. Sinclair

When the Sir2 enzyme is sitting on the mating-type genes, they remain silent and the cell continues to mate and reproduce. But when a DNA break occurs, Sir2 is recruited to the break to remove the acetyl tags from the histones at the DNA break. This bundles up the histones to prevent the frayed DNA from being chewed back and to help recruit other repair proteins. Once the DNA repair is complete, most of the Sir2 protein goes back to the mating-type genes to silence them and restore fertility. That is, unless there is another emergency, such as the massive genome instability that occurs when ERCs accumulate in the nucleoli of old yeast cells.

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.

you were a member of the American upper middle class in the 1970s, you weren't just enjoying a more affluent life, you had a longer one, too. Those in the top half of the economy were living an average of 1.2 more years than those in the bottom half. By the early 2000s, the difference had increased dramatically. Those in the upper half of the income spectrum could expect nearly six additional years of life, and by 2018, the divide had widened, with the richest 10 percent of Americans living thirteen more years of life than the poorest 10 percent.40