Graphical Abstract. Using two serum-donor cohorts consisting of a middle-aged to old cohort (MATO) and a cohort with young and old participants, we investigated the effect of ageing human serum on hippocampal progenitor cells. Firstly (1) using the MATO cohort, we show that participant hippocampal volumes are strongly associated to age. Second (2), using serum from both cohorts, we employ a novel in vitro assay to assess the effect of ageing serum on in vitro neurogenesis. To this end, immunostaining for markers of neurogenesis was carried out alongside a microarray analysis focused on identifying the molecular hallmarks of ageing. Interestingly, by combining results obtained in (1) and in (2) we show that neuroblast number following the application of serum is predictive of larger hippocampal subfield volumes of the corresponding serum donors. In addition (3), we use medical records of older participants to test for association between in vivo and in vitro phenotypes. We report an association between cognitive decline of older participants and Map2 positive cells. Finally, using the young and old cohort we show that age is associated to cell death following the in vitro assay.