Lifespan: The Revolutionary Science of Why We Age—and Why We Don't Have To

by David A. Sinclair

In 2006, the Japanese stem cell researcher Shinya Yamanaka announced to the world that after testing dozens of combinations of genes, he had discovered that a set of four—Oct4, Klf4, Sox2, and c-Myc—could induce adult cells to become pluripotent stem cells, or iPSCs, which are immature cells that can be coaxed into becoming any other cell type. These four genes code for powerful transcription factors that each controls entire sets of other genes that move cells around on the Waddington landscape during embryonic development. These genes are found in most multicellular species, including chimpanzees, monkeys, dogs, cows, mice, rats, chickens, fish, and frogs. For his discovery, essentially showing that complete cellular age reversal was possible in a petri dish, Yamanaka won the Nobel Prize in Physiology or Medicine along with John Gurdon in 2012. We now call these four genes Yamanaka factors.

Yamanaka's experiments