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Plot
On her 50th birthday, once-celebrated but now-faded Hollywood movie star Elisabeth Sparkle is unceremoniously dismissed from the long-running aerobics TV show she hosts, with producer Harvey citing her advanced age as the reason. While driving home, Elisabeth is distracted by a billboard of herself being taken down, resulting in a major car crash. At the hospital, a young male nurse seems preoccupied with her back and gives her a flash drive advertising The Substance, a black market serum that generates a "younger, more beautiful, more perfect" version of oneself. After some deliberation, Elisabeth orders The Substance and injects the single-use activator serum, resulting in a much younger version of herself emerging from a slit in her back.
The Substance establishes a symbiotic relationship between the two bodies: Elisabeth must transfer her consciousness between the bodies every seven days without exception, while the inactive body remains unconscious. The other self also requires daily injections of "stabilizer fluid" extracted from the original body via a lumbar puncture to prevent deterioration. The other self names herself Sue and is quickly hired as Elisabeth's replacement by Harvey. Her new TV show skyrockets her to fame, and she is eventually selected to host the broadcaster's major New Year's Eve show. Sue enjoys a confident and hedonistic lifestyle, but becomes an insecure recluse when living as Elisabeth.
After a one-night stand, Sue extracts extra stabilizer fluid from Elisabeth to extend the evening's sexual activities. The next morning, Elisabeth wakes to find that her index finger has aged rapidly. She calls the supplier, who warns her that staying as Sue longer than seven days causes irreversible rapid aging of her original self, and Elisabeth must follow the switching schedule to prevent this from happening again. Despite being a single consciousness, both personas begin viewing themselves as separate individuals and quickly grow to despise each other; Elisabeth becomes jealous of Sue's beauty and success, resenting her frequent disregard of the switching schedule, whereas Sue is appalled by Elisabeth's constant self-loathing and binge eating. Following a particularly self-destructive episode as Elisabeth, a disturbed Sue refuses to switch back and stockpiles stabilizer fluid from Elisabeth in glass jars, deciding to remain as Sue permanently.
Three months later, the day before the New Year's Eve telecast, Sue is unable to replenish her stabilizer fluid as Elisabeth's body is completely drained of it. The supplier informs her that the only way to replenish the fluid is by switching back to her original self. When they switch, Elisabeth finds herself horrifically transformed into a deformed hunchback. Desperate to stop Sue's stabilizer abuse from further degrading her body, Elisabeth acquires a serum designed to terminate Sue. However, still craving admiration, she stops before injecting the full syringe of termination serum and resuscitates Sue, disrupting their symbiotic balance and leaving both forms fully conscious. Realizing Elisabeth's intent upon seeing the near-empty termination syringe, Sue flies into a rage and brutally beats Elisabeth to death before leaving to host the New Year's special.
Without Elisabeth, Sue's body begins to rapidly deteriorate. In a panic, Sue rushes to her apartment and tries to create a new version of herself with the leftover activator serum, something expressly forbidden by the supplier; this inadvertently turns her into a grotesque hybrid of Elisabeth and Sue, and she nevertheless dresses up and goes to the live broadcast wearing an improvised mask cut from a painting of Elisabeth in her heyday. As she limps onto the stage and starts to speak to the audience, the mask falls off, causing the horrified audience to erupt into violent chaos; a man decapitates her before her body drenches the audience with blood. What is left of her escapes the studio and collapses into a pile of internal organs. Elisabeth's original face detaches from the pile, crawls onto her neglected star on the Hollywood Walk of Fame, and gazes up at the night sky. She smiles as she hallucinates being admired by everyone around her before melting into a pool of blood. The next day, the blood is cleaned up by a floor scrubber.
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