Abstract: When I gave my Harvey lecture, which was a great honor for me, I told the story of our efforts to understand aging. We began our studies in the early 1990s. At that time, and for years before, many people assumed that aging was a haphazard process, not subject to regulation. Our tissues just break down, and we die. But the more I thought about it, the more I started to question this view. A mouse lives two years, whereas a bat can live 30 years or more. A rat lives three years; a squirrel, 25 (Fig. 2.1). These animals differ by their genes, so there must be genes that affect aging. Also, nothing in biology seems to “just happen”; everything seems to be regulated, often in quite an extraordinary way. My experience as a developmental biologist sharpened my thoughts about aging. People were once very skeptical about looking for developmental genes. Treating frog embryos with acid can produce a second head, and inhibiting pyrimidine synthesis in flies produces small wings, so many people thought that genes affecting development would also affect things like the Krebs cycle, or pH. They were wrong. There is a dedicated regulatory circuitry for pattern formation. In addition, many people thought that developmental mechanisms would differ completely in different kinds of animals, but again they were wrong. In fact, the degree of evolutionary conservation is striking. So it seemed to me that something as fundamental as aging might also be subject to regulation. Maybe there would be a molecular longevity “dial,” like a thermostat, that is universal but set to run at different rates in different kinds of animals. The dial would be turned up in mice (which age quickly) and