In this solo episode of Lifespan, Dr. David Sinclair answers the question he's asked more than any other—if you could do one thing to live longer, what would it be?—with a simple answer: eat less often. He unpacks the science of caloric restriction and fasting, two overlapping practices that together represent the most potent and reproducible way to extend lifespan in animals, and lays out the benefits seen in studies, from lower blood pressure and body weight to sharper memory and a measurable slowing of the pace of aging. To understand why modern eating is so hard on us, he travels back 100,000 years to the diets of our ancestors—including Neanderthals, whose genes many of us still carry—and explains the thrifty-genotype and evolutionary-mismatch hypotheses behind why some of us store fat so easily.

From there, Dr. Sinclair follows the story into the present: gene variants like TCF7L2 and THADA that shaped how our bodies handle food and warmth, and the surprising history of how we came to eat three meals a day plus snacks. It turns out much of it traces not to science but to marketing—from a 1917 Kellogg's slogan that crowned breakfast “the most important meal of the day” to a flawed 1964 study that launched the eat-all-day mindset and the snack culture that followed. Along the way he revisits Luigi Cornaro's Renaissance experiment in sober living and sets the stage for the science of caloric restriction, a practice that has been extending the lifespan of animals for nearly a century.