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.
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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. She falls to the floor and convulses as her body generates a younger version of herself that splits out of 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 and is fed intravenously with a provided weekly food supply. 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.
Nearing the end of the her seven days in the other her, Sue goes out to party and brings a man home. Wanting to enjoy the night just a little more, she extracts extra stabilizer from Elisabeth, putting her past the seven day cycle as Sue.
The next morning, Elisabeth wakes in her body to find that her index finger has aged rapidly. She calls the supplier, who warns her that staying in the other her longer than seven days causes irreversible rapid aging of her original self, and Elisabeth must "respect the balance" and follow the switching schedule to prevent this from happening again.
Elisabeth finds it harder to look in the mirror in her original body and begins to hate herself more and more, becoming a recluse and giving up on any acting career or social life of her own. She begins binge eating and watching TV, wasting time as she waits to become Sue again.
As Sue, she is disgusted with the older version of herself who sits around and leaves a mess for her to clean up.
As she gains more success, she remains as Sue longer and longer, only to suffer advance and uneven aging across her entire body once she finally does switch to Elisabeth.
Despite being a single consciousness, both personas have begun viewing themselves as separate individuals, and Elisabeth is furious with Sue, calling her a selfish bitch for stealing so much time from her.
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