I have a $1 billion wager on whether by the year 2150 at least one person will have lived to the age of 150 years. In the more than twenty years since I made the wager, no one has approached the longevity record of 122 years set by Jeanne Calment back in 1997. Yet, I remain optimistic about my chances of winning. This talk will describe four emerging biomedical breakthroughs that support my optimism. There are also reasons to be cautious in one's optimism, mainly having to do with flaws in the way that basic biological breakthroughs are translated to the clinic and the community. My talk will not only describe these emerging breakthroughs but will also elaborate on flaws in our current translational approaches and how to overcome those flaws.