Pilot Trial of Fisetin in Healthy Volunteers and Older Patients With Multimorbidity

Healthy volunteers: Inclusion Criteria: * Aged 20-35 years * suPAR levels \<3.5 ng/mL (± 15% corresponding to assay variation) * Able to cooperate cognitively * Able to read and understand Danish * Women of childbearing potential must use effective contraception Exclusion Criteria: * Body weight \>100 kg * Inability to swallow pills * Pregnant and/or lactating * Known hypersensitivity or allergy to fisetin or excipients in the placebo capsules * Presence of any condition that the investigator believes would put the subject at risk or would preclude the participant from successfully completing all aspects of the trial * Presence of known chronic diagnosis * Active acute illness * Prescribed medication, except contraceptives * Previous cancer diagnosis or treatment * Use of senolytic and other "anti-aging" supplements Older patients with multimorbidity: Inclusion Criteria: At screening #1 during hospital admission: * Acutely hospitalized medical patient * Age ≥65 years * suPAR \>5 ng/mL (± 15% corresponding to assay variation) * Multimorbidity (≥2 chronic diagnoses) * Able to cooperate cognitively * Able to read and understand Danish At screening #2 28 days after hospital discharge: * suPAR \>5 ng/mL (± 15% corresponding to assay variation) Exclusion Criteria: At screening #1 during hospital admission: * Body weight \>100 kg * Inability to swallow pills * Known human immunodeficiency virus infection, active hepatitis B or C infection, invasive fungal infection * Uncontrolled (as per clinical judgment) pleural/pericardial effusions or ascites * New/active invasive cancer except non-melanoma skin cancers * Active cancer treatment or disseminated cancer * Known condition associated with major immunodeficiency * Known hypersensitivity or allergy to fisetin or excipients in the placebo capsules * Use of senolytic and other "anti-aging" supplements At screening #2 28 days after hospital discharge: * Body weight \>100 kg * CRP \>30 mg/L (± 15% corresponding to assay variation) * Inability to swallow pills * Presence of any condition, or abnormal routine biochemistry test, that the investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial * Unstable (as per clinical judgment) major disorders, e.g., cardiovascular, renal, endocrine, immunological, hepatic disorder, or cancer * Estimated glomerular filtration rate (eGFR) \<15 ml/min/1.73 m2 or as per clinical judgment (e.g., risk of acute kidney injury) * Human immunodeficiency virus infection, known active hepatitis B or C infection, invasive fungal infection * Uncontrolled (as per clinical judgment) pleural/pericardial effusions or ascites * New/active invasive cancer except non-melanoma skin cancers * Active cancer treatment or disseminated cancer * Known condition associated with major immunodeficiency * Known hypersensitivity or allergy to fisetin or excipients in the placebo capsules * Subjects taking strong inhibitors or inducers of CYP3A4 or as per clinical judgment * Subjects taking specified substrates with a narrow therapeutic range for CYP3A4 or as per clinical judgment * Subjects taking specified inhibitors, inducers, or substrates of CYP2D6, CYP2C9, or CYP2C8, or as per clinical judgment * Subjects regularly using drug classes or specific medications or as per clinical judgment * Use of senolytic and other "anti-aging" supplements