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Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells

Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT, Usc INRA) ISTAB Avenue des Facultés Université Bordeaux 1, 33405 Talence, ¹ Service de Biochimie de l’Hôpital Pellegrin, Hôpitaux de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, Place Amélie Raba Leon, 33000 Bordeaux and ² INSERM U593 Université Victor Ségalen Bordeaux 2, 146 Rue Leo Saignat, 33076 Bordeaux Cedex, France

(Correspondence should be addressed to V Pallet; Email: v.pallet{at}istab.u-bordeaux1.fr)

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 (RAR, RAR and RXR) and thyroid (TR and TRß) 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: RAR 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 ( as well as ß 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.

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				F. Mingaud, C. Mormede, N. Etchamendy, N. Mons, B. Niedergang, M. Wietrzych, V. Pallet, R. Jaffard, W. Krezel, P. Higueret, et al. Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice J. Neurosci., January 2, 2008; 28(1): 279 - 291. [Abstract] [Full Text] [PDF]