Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells.
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 (RARalpha, RARgamma and RXRalpha) and thyroid (TRalpha and TRbeta) 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
RARgamma 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 (alpha as well as beta subtypes) was significantly decreased in the elderly.


CONCLUSIONS
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.
Feart
C
C
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT, Usc INRA) ISTAB Avenue des Facultés Université Bordeaux 1, 33405 Talence, France.
Pallet
V
V
Boucheron
C
C
Higueret
D
D
Alfos
S
S
Letenneur
L
L
Dartigues
J F
JF
Higueret
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood; D018168:Receptors, Retinoic Acid / Q000097:blood* / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000097:blood* / Q000235:genetics; D012016:Reference Values; D012176:Retinoids / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013972:Thyrotropin / Q000097:blood; D000097768:Retinoic Acid Receptor gamma
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012176:Retinoids; D013972:Thyrotropin; D000097768:Retinoic Acid Receptor gamma