Cyclophilin D regulates lifespan and protein expression of aging markers in the brain of mice

•Diminished expression but not complete absence of cyclophilin D increases lifespan in mice.•Partial or complete deletion of cypD alters the expression of aging markers in the mouse brain.•Partial or complete deletion of cypD does not alter the behaviour of aged mice.

Cyclophilin D (cypD) modulates the properties of the permeability transition pore, a phenomenon implicated in the manifestation of many diseases including aging. Here, we examined the effects of partial or complete deletion of cypD on i) lifespan, ii) forebrain protein expression of 18 aging markers as well as regional expression of GFAP, mGluR1, and alpha-synuclein, and iii) behaviour of aged (> 24 month) male and female mice. Both male and female cypD heterozygous but not KO mice exhibited increased lifespans compared to WT littermates, associated with alterations in the protein expression of some markers, albeit without exhibiting changes in behaviour.