Reduced circulating progenitor cells in older adults with major depression: Evidence of accelerated biological aging

Major depression (or late-life depression [LLD]) is a prevalent and debilitating condition among older adults and is increasingly recognized as a contributor to accelerated biological aging. LLD has been associated with aging-related phenotypes, namely chronic inflammation and cellular senescence. However, stem and progenitor cell exhaustion, another pivotal hallmark of biological aging, remains understudied in this context. In this study, we investigated the absolute count and frequency of circulating progenitor cell populations in peripheral blood mononuclear cells (PBMC) of 38 older adults (LLD, n=19; control, n=19). CD34+ cell enrichment increased the detectable number of progenitor cells by 30- to 50-fold compared to unselected PBMCs. Individuals with LLD had significantly lower counts of endothelial progenitor cells (EPC; β= -0.95 [-1.57 - -0.33], p=0.003), and very small embryonic-like stem cells (vSEL; β= -1.61 [-2.65 - -0.58], p=0.002). Additionally, vSELs count negatively correlated with the severity of depressive symptoms (r= -0.34, p=0.034). These findings suggest that LLD is associated with reduced circulating progenitor cells, supporting the hypothesis that depression contributes to accelerated biological aging in older adults. • Late-life depression is associated with reduced circulating progenitor cell populations, including EPCs and vSELs. • CD34 + enrichment improved detection of rare progenitor cells by 30- to 50-fold over unselected PBMCs. • vSEL counts negatively correlated with depressive symptom severity, linking progenitor cell loss to clinical outcomes. • Findings support stem cell exhaustion as a potential biological aging mechanism in late-life depression