Background: Inadequate retinoid status has often been described as occurring with aging. Moreover, subclinical hypothyroid status has also been evoked in the elderly. Several studies performed in animals have described the crucial incidence of age-related hypo-functioning of retinoid and thyroid signalling pathways, particularly in the brain.Objective: The aim of the present study was to clarify whether aging modifies retinoid and thyroid signalling in humans.Methods: Using real-time RT-PCR the relative amount of mRNA of the retinoid (RARα, RARγ and RXRα) and thyroid (TRα and TRβ) nuclear receptors in peripheral blood mononuclear cells (PBMC) of young (24–57 years old,n= 22) compared with elderly (69–90 years old,n= 24) healthy subjects was quantitated. Classical plasma parameters used to characterize the retinoid and thyroid status – retinol (ROH), retinol-binding protein (RBP), free triiodothyronine (FT3) and thyroxine (FT4), thyroid-stimulating hormone (TSH) and transthyretin (TTR) – were also assessed.Results: RARγ expression was significantly decreased in elderly versus young subjects while no modification of the retinoid-related plasma parameters ROH and RBP were emphasized by aging. Concerning thyroid criteria, the elderly exhibited an increase in TSH concentration (+39%) without significant modifications of FT3 and FT4, which indicated an age-related sub-clinical hypothyroidism. Concurrently, the amount of TR mRNA (α as well as β subtypes) was significantly decreased in the elderly.Conclusion: These data constitute the first evidence of an age-related hypo-activation of the retinoid and thyroid nuclear pathways in PBMC. Further study of the possible association between the expression of the retinoid and thyroid nuclear receptors and age-related cognitive alterations in humans would be interesting.