In SAMP8 mice, a model of accelerated aging, males and females followed distinct trajectories of hippocampal neurogenesis despite comparable cognitive performance at six months. The diterpenoid compound ER272 was associated with improved cognition and preservation of neurogenic parameters in males only, with limited effect in females. The findings indicate that sex modifies both the biology of brain aging and the response to interventions aimed at slowing it.
Key Points
- Male and female SAMP8 mice show divergent hippocampal neurogenesis trajectories
- ER272 improved cognition and neurogenesis in males only
- Mixed-sex cohorts can obscure biologically meaningful aging differences
Longevity Analysis
Cognitive aging interventions are routinely validated in male-dominant or pooled cohorts, and this work demonstrates how that design can conceal opposing responses between sexes. Hippocampal neural stem cell reserve is governed in part by hormonal signaling, which diverges sharply across the lifespan, so a compound that preserves regenerative capacity in one sex may offer nothing in the other. For anyone translating preclinical neuroprotection data into practice, the operative question is not whether an agent supports brain regeneration, but in whom — and equivalent performance on cognitive testing does not imply equivalent underlying biology.
Original published by Wiley Aging Cell, by Ricardo Gómez‐Oliva, Andrea Chamorro‐Francisco, Isabel Atienza‐Navarro, Livia Carrascal, María D. Freire‐Aragón, Rosario Hernández‐Galán, Pedro Nunez‐Abades, Mónica García‐Alloza, Carmen Castro .