Age-related declines in stem cell function in the body and central nervous system of rodents can be reversed by exposure to a youthful systemic milieu. Conversely, the old milieu inhibits stem cell function in young rodents. In this study, allogeneic human serum from old healthy individuals induced an increase in apoptotic cell death of human hippocampal progenitor cells when compared to serum from young subjects. General Linear Models revealed variability in markers of proliferation and differentiation was partly attributable to intake of antihypertensive medication and very mild cognitive decline among older subjects. An endophenotype approach revealed upregulation of established and novel ageing molecular hallmarks in response to old serum following whole-genome expression arrays. interestingly, serum from older subjects induced a wide range of cellular and molecular phenotypes, likely reflecting the cumulative effect of health exposures and inequalities during a lifetime. Data will also be presented on how serum of mild cognitively impaired patients differentially alters human hippocampal progenitor cell fate to predict conversion to Alzheimer’s Disease.