Whether aging or Parkinson's disease (PD) affects the responses of peripheral blood mononuclear cells (PBMCs) to immunosuppression by bone marrow-derived mesenchymal stem cell (BM-MSCs) and which cytokines are more effective in inducing BM-MSCs to be immunosuppressive remains to be elucidated. PBMCs were isolated from healthy young (age 26-35), healthy middle-aged (age 56-60) and middle-aged PD-affected individuals. All the recruits were male. The mitogen-stimulated PBMCs and proinflammatory cytokine-pretreated BM-MSCs were co-cultured. The PBMC proliferation was measured using Cell Counting Kit-8, while the cytokine secretion was assayed by cytometric bead array technology. The immunosuppressive ability of BM-MSCs was confirmed in young healthy, middle-aged healthy and middle-aged PD-affected individuals. Among the three groups, the PBMC proliferation and cytokine secretion of the young healthy group were suppressed more significantly compared with those of the middle-aged healthy and middle-aged PD-affected group. No significant differences were identified in the PBMC proliferation and cytokine secretion between the patients with PD and the middle-aged healthy subjects. Interferon (IFN)- synergized with tumor necrosis factor (TNF)-, interleukin (IL)-1 or IL-1 was more effective than either one alone, and the combinations of IFN- + IL-1 and IFN- + IL-1 were more effective than IFN- + TNF- in inducing BM-MSCs to inhibit PBMC proliferation. The results of the present study suggested that aging, rather than PD, affects the response of PBMCs toward the suppression of BM-MSC, at least in middle-aged males. Patients with PD aged 56-60 remain eligible for anti-inflammatory BM-MSC-based therapy. Treatment of BM-MSCs with IFN- + IL-1 or IFN- + IL-1 prior to transplantation may result in improved immunosuppressive effects.