Titus was one of only about 700 mountain gorillas left in Africa.The highly endangered animals are found only on the slopes of the Virunga mountains on the borders of Rwanda, Uganda and the Democratic Republic of Congo.
The plight of the mountain gorilla was brought to the attention of the world by Fossey, who lived in the Virunga until her murder in 1985.
"He was born on 24 August 1974 and has been observed closely by researchers throughout his entire life," a statement from the Rwandan national parks office said. "Tragically, he succumbed to old age on September 14."
The life expectancy of a healthy gorilla is about 40.
The silverback's story was featured last year in a BBC documentary called Titus: The Gorilla King.
He rose to become the dominant male in his group despite losing family members and being born underdeveloped.
"Every gorilla death recorded is not only a great loss, but a major setback to conservation efforts of removing the mountain gorillas off the endangered species list," tourism officials said.
Gorilla tracking is now the mainstay of tourism in Rwanda and Uganda.
© BBC MMIX
Here's a relevant Little Mo poem and illustration, from The Concrete Jungle Book: