While these "dramatically human experiences" take different forms, they nonetheless "raise the pressing question of the meaning of life," he said.
When faced of these experiences, some may become cynical, "as if the only solution were simply to put up with these experiences, trusting only in our own strength," the Pope said.
Others, meanwhile, may put their trust in science with the belief that medicine has a cure, despite the fact that this is not always the case, he said.
Francis drew from the day's Gospel account of the woman caught in adultery who, like persons who are sick and disabled, is cast aside by society.
"Jesus accepts and defends her," and "is attentive to her suffering and her plea," the Pope explained.
His tenderness toward the woman "is a sign of the love that God shows to those who suffer and are cast aside."
In addition to physical suffering, the pontiff spoke also of spiritual suffering, which he described as "one of today's most frequent pathologies."
"It is a suffering of the heart; it causes sadness for lack of love," he said. "When we experience disappointment or betrayal in important relationships, we come to realize how vulnerable and defenseless we are."
"The temptation to become self-absorbed grows stronger, and we risk losing life's greatest opportunity: to love in spite of everything."
The pontiff stressed that Jesus, through his passion, loved us to the end, and understands our suffering because he experienced it himself.
"Can we reproach God for our infirmities and sufferings when we realize how much suffering shows on the face of his crucified Son?" he said.
"Jesus is the physician who heals with the medicine of love, for he takes upon himself our suffering and redeems it. We know that God can understand our infirmities, because he himself has personally experienced them."
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"The way we face suffering and limitation is the measure of our freedom to give meaning to life's experiences, even when they strike us as meaningless and unmerited."
In our weakness we are strengthened and receive what we need in Christ's suffering for "his body, the Church," Francis said, concluding his homily.
"For that body, in the image of the risen Lord's own, keeps its wounds, the mark of a hard struggle, but they are wounds transfigured for ever by love."
At the conclusion of the Mass, before leading those present in the weekly Angelus prayer, Pope Francis issued a special thanks to all those who traveled from throughout Italy and other countries to take part in the Jubilee for the sick and persons with disabilities.
"Thank you especially, you have wanted to be present in your conditions of illness or disability," he told those present.
The Pope also extended his "heartfelt thanks" to doctors and healthcare professionals, who set up "Health Points" at the four papal basilicas in Rome, including St. Peter's Basilica, and who offered specialized tours for hundreds of people.