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Jesus' second sentence makes the meaning of His first sentence even more clear:
For whoever wishes to save his life shall lose it; but whoever loses his life for My sake and the gospel's shall save it (Mark 8:35).
Again, notice this sentence begins with "For," relating it with the first sentence, adding clarification. Here Jesus contrasts two people, the same two people who were implied in the first sentence—the one who would deny himself and take up his cross to follow Him and the one who would not. Now they are contrasted as one who would lose his life for Christ and the gospel's sake and one who would not. If we look for the relationship between the two, we must conclude that the one in the first sentence who would not deny himself corresponds to the one in the second sentence who wishes to save his life but will lose it. And the one in the first sentence who was willing to deny himself corresponds to the one in the second sentences who loses his life but ultimately saves it.
Jesus was not speaking about one losing or saving his physical life. Later sentences in this passage indicate that Jesus had eternal losses and gains in mind. A similar expression by Jesus recorded in John 12:25 says, "He who loves his life loses it; and he who hates his life in this world shall keep it to life eternal" (emphasis added).
The person in the first sentence who would not deny himself was the same person in the second sentence who wished to save his life. Thus we can reasonably conclude that "saving one's life" means "saving one's own agenda for his life." This becomes even clearer when we consider the contrasted man who "loses his life for Christ and the gospel's sake." He is the one who denies himself, takes up his cross, and gives up his own agenda, now living for the purpose of furthering Christ's agenda and the spread of the gospel. He is the one who will ultimately "save his life." The person who seeks to please Christ rather than himself will ultimately find himself happy in heaven, while the one who continues to please himself will ultimately find himself miserable in hell, there losing all freedom to follow his own agenda.