Huge Sekiro spoilers ahead.
In Buddhism, the three marks of existence are impermanence, non-self and suffering. It's our failure to accept these things that leads to Samsara: an endless, painful cycle of reincarnation and an aimless wandering through a ceaseless existence.
Like weeping over wilted cherry blossoms when autumn arrives, we struggle against transience, and so we suffer. We cling onto fixed identities in ourselves and others, expecting to step into Heraclitus' river over and over, and so we suffer. Perhaps most painfully, we reject suffering itself, treating its presence in our lives as a failure, rather than a natural occurrence. And so we suffer.