Abstract
Diarylpropionitrile (DPN) is an estrogen receptor-β specific agonist with neuroprotective and anti-cancer properties, including improved maintenance of cognitive function with advanced age, the suppression of anxiety-like behaviours, and the inhibition of cancer cell growth. We hypothesized that DPN would affect lifespan. This hypothesis was tested in ovariectomized female mice, which model post-reproductive women. Estrogen receptor-β agonists are already in use to treat symptoms of menopause in this population. DPN was delivered in the diet at a dose corresponding to approximately 3mg/kg mouse body mass/day. During the study, we monitored DPN’s effect on body mass, anxiety-like behaviours, learning, memory, frailty, and survivorship. In comparison to controls, DPN-treated mice showed reduced anxiety-like effects at two months of treatment (9 months of age) and there was a possibility (p = 0.08) that this effect was maintained at more advanced ages. DPN-fed mice also exhibited improved spatial learning and memory at 28 months of age. They gained more weight over the course of the study and showed differences in the relationship between age and frailty. Despite increased weight gain, DPN-treated mice showed no deficits in the propensity to run or mean velocity during running events when tested in single wheel chambers. Although there was no significant effect on lifespan parameters, DPN-fed mice took longer to reach the 25%, 50%, 75% and 100% mortality quartiles (n=25). Based on these findings, we believe that dietary DPN administration shows promise as an anti-aging intervention and warrants further investigation in a larger study.