The present invention provides for systems and methods for inhaled CO therapy to prevent, attenuate, or delay processes that accelerate the loss of organ or tissue function, thereby increasing the lifespan of transplanted organs or tissues, or slowing the decline of native organs or tissues, or delaying the need for replacement of diseased native organs with organ transplants. Such biological processes that are prevented, attenuated, or delayed include chronic persistent inflammation, fibrosis, scarring, as well as immunologic or autoimmune attack.