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Aging is associated with changes in thyroid gland physiology. Age-related changes in the contribution of peripheral tissues to thyroid hormone serum levels have yet to be systematically assessed. Here, we investigated age-related alterations in the contributions of the liver and kidney to thyroid hormone homeostasis using 6-, 12-, and 24-mo-old male Wistar rats. A significant and progressive decline in plasma thyroxine occurred with age, but triiodothyronine ([T.sub.3]) was decreased only at 24 mo. This was associated with an unchanged protein level of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the kidney and with a decreased MCT8 level in the liver at 24 mo. Hepatic type I deiodinase (D1) protein level and activity declined progressively with age. Renal D1 levels were decreased at both 12 and 24 mo but D1 activity was decreased only at 24 mo. In the liver, no changes occurred in thyroid hormone receptor (TR) TR[[alpha].sub.1], whereas a progressive increase in TR[[beta].sub.1] occurred at both mRNA and total protein levels. In the kidney, both TR[[alpha].sub.1] and TR[[beta].sub.1] mRNA and total protein levels were unchanged between 6 and 12 mo but increased at 24 mo. Interestingly, nuclear TR[[beta].sub.1] levels were decreased in both liver and kidney at 12 and 24 mo, whereas nuclear TR[[alpha].sub.1] levels were unchanged. Collectively, our data show differential age-related changes among hepatic and renal MCT8 and D1 and TR expressions, and they suggest that renal D1 activity is maintained with age to compensate for the decrease in hepatic [O.sub.2] production. aging; deiodinase; liver; kidney

Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an apriori definition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in 'omics' are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity., 1. Introduction Genomic and proteomic data analyses have proven to be essential for an understanding of the underlying factors involved in human disease and for the discovery of diagnostic biomarkers, [...]