MacLaine, well-known for her belief in life after death, spoke seriously about the roles of women in movies, and was gently teased about her thoughts on previous lives by co-stars such as Jack Nicholson and Carrie Fisher at the gala dinner on the movie studio lot of Sony Pictures.
She even made light of her ideas, telling the audience of A-list stars to relax and enjoy themselves during this life "because if we don't do it now, we'll do it next time around."
MacLaine added: "If you enter my life, you'll never get out, even when you die."
The evening featured film clips highlighting MacLaine's movies such as "The Apartment," "Sweet Charity," and "The Turning Point" and speeches from MacLaine's fellow stars.
The Los Angeles-based American Film Institute, or AFI, is a leading education and preservation group in the United States. Past AFI lifetime honorees have included Nicholson, Sidney Poitier, Steven Spielberg, Meryl Streep, Morgan Freeman and MacLaine's brother Warren Beatty, all of whom were there.
Beatty said he was pleased to honor "a person I have known, a person whom I have loved my whole life" while Fisher called MacLaine "some future person's past life."
Streep, who co-starred with MacLaine in "Postcards From the Edge," presented the award to the actress.
"You're the one who cut the path for all of us," she said. "Because you have done some of your greatest work and your most successful stuff -- ‘Turning Point,' ‘Being There,' ‘Terms of Endearment,' ‘Madame Sousatzka,' ‘Postcards,' ‘Steel Magnolias'-- in what we call ‘middle age.' You're writing the template on how to have a challenging, creative later career. That gives hope to everybody, not just actors."
MacLaine, 78, thanked many people, including Streep, Jennifer Aniston, Sally Field and Melanie Griffith for being "my compadres, my other half of the sky, my belief that women who speak the truth will make the world a better place."
She also thanked her male co-stars, "those that I've made love to on-screen and those I've made love to off-screen."
Turning to her younger brother Beatty, she called him the person "I've known the longest and loved the longest."
She reminisced about her childhood and her parents, and told the audience to "listen to the women in our lives." She also thanked "the men, for the feminine in themselves."
MacLaine was the AFI award's 40th recipient. The ceremony will be broadcast by cable network TVLand on June 24.
(Editing by Bob Tourtellotte and Dale Hudson)
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