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Preclinical studies have demonstrated beneficial effects of proteasome activation in models of heart failure and ischemiareperfusion injury, 69 further supporting ER proteostasis as a therapeutically actionable axis

Common side effects Mild and transient: Headache (most common) Nasal irritation (intranasal route) Drowsiness or fatigue Mild dizziness Dry mouth or throat These effects typically resolve within hours and often diminish with continued use as tolerance develops

However, aging and lifestyle factors are ongoing, so many patients choose maintenance protocols

Data availability Source data underlying graphs presented in the main figures can be found in Supplementary Data 1 and are available from the corresponding author on reasonable request