Neuro-Oncology · Oct 2026
176 Exploring Effects of Geroprotectors on Brain Neurophysiology Through the ‘REsilience PROmotion with GeRoprotectors: AssessMent of biological effect’ (REPROGRAM) Trial
By Nixon A, Acharjee A, Duggal NA et al.
Abstract Introduction Resilience to physiological stressors, including neurosurgery, is a key determinant of healthspan. ‘Geroprotectors’ target biological hallmarks of ageing—including cellular senescence, dysregulated autophagy, and mechanistic target of rapamycin (mTOR) signalling—and may improve resilience. Although peripheral biomarkers in blood and adipose tissue are accessible, assessing brain-specific effects is challenging due to limited central sampling and the blood–brain barrier. Electroencephalography (EEG) provides non-invasive, real-time measurement of neural oscillatory dynamics, serving as a biological systems-level proxy of brain function. Age-related changes in oscillatory activity during lexical processing offer a sensitive paradigm for detecting neurophysiological modulation. As part of the REPROGRAM trial, this sub-study aims to determine whether a three-week geroprotector intervention (metformin, fisetin, or spermidine) alters neural oscillatory patterns in healthy older adults. A secondary objective examines whether EEG changes correspond with shifts in peripheral biological ageing biomarkers. Methods Sixty healthy adults (≥70 years) are randomised to one of three daily interventions for three weeks: metformin modified-release (1500 mg), fisetin (100 mg), or spermidine (15 mg). Biomarkers reflecting hallmarks of ageing are assessed in blood and adipose tissue pre- and post-intervention. EEG recordings are acquired at baseline and follow-up during resting state (eyes closed) and during a lexical retrieval and semantic binding task sensitive to age-related change. Analyses will evaluate within-subject changes in oscillatory activity and explore associations between neural and peripheral biological measures. Results Data analysis (n = 60; 30 female) is scheduled for autumn 2026. Conclusions Measurable changes in brain neurophysiology are evaluated alongside peripheral biological ageing markers following short-term geroprotector interventions. Findings will inform mechanisms of brain ageing amenable to pharmacological modulation, supporting development of prehab interventions to improve healthspan of neuro-oncology populations following physiological stressors (surgery; radiotherapy; chemotherapy).