Long‐term D‐galactose Administration Mimics Natural Aging in Rat’s Hippocampus

Abstract Background D‐galactose has been widely used for an induction of premature aging in laboratory animals (1). However, it was observed that short‐term administration of D‐galactose failed to induce some aging phenomena (2). Therefore, we aimed to determine whether long‐term administration of D‐galactose could mimic natural aging of the rat’s hippocampus, based on the primary, antagonistic, and integrative hallmarks of aging. Method Seven‐week‐old male Wistar rats (n = 12) were randomly injected with either normal saline as vehicle (n = 6) or 150 mg/kg/day of D‐galactose subcutaneously for 28 weeks. Seventeen‐month‐old male Wistar rats (n = 6) were also included as the naturally aged controls. At the end of week 28 of the experiment (when the rats were 35 weeks old for D‐galactose‐induced aging and 24 months old for natural aging), all rats were sacrificed for brain collection. The, the hippocampus was examined for molecular studies. Result Long‐term D‐galactose administration demonstrated the features of natural aging in the hippocampus of young rats. These include loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication (Figure A) . In the context of cognitive function, natural aging and long‐term D‐galactose administration similarly impaired hippocampal learning and memory, as indicated by reducing the novel object location and recognition tests (Figure B, C) . Conclusion Long‐term administration of D‐galactose‐induced aging potentially mimic natural aging process of the hippocampus. These findings suggest that long‐term administration of D‐galactose is suitable for an establishment of the aging model in young animals. Reference 1. Shwe T, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Role of D‐galactose‐induced brain aging and its potential used for therapeutic interventions. Exp Gerontol. 2018;101:13‐36. 2. Cardoso A, Magano S, Marrana F, Andrade JP. D‐Galactose High‐Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats. Rejuvenation research. 2015;18(6):497‐507.