title: (Healthy) ageing: focus on iodothyronines.
abstract: The activity of the thyroid gland diminishes during ageing, but a certain tissue reserve of T3 and its metabolites is maintained. This reserve is thought to play a regulatory role in energy homeostasis during ageing. This review critically assesses this notion. T3 was thought to act predominantly through pathways that require transcriptional regulation by thyroid hormone receptors (TRs). However, in recent years, it has emerged that T3 and its metabolites can also act through non-genomic mechanisms, including cytosolic signaling. Interestingly, differences may exist in the non-genomic pathways utilized by thyroid hormone metabolites and T3. For instance, one particular thyroid hormone metabolite, namely 3,5-diiodo-L-thyronine (T2), increases the activity of the redox-sensitive protein deacetylase SIRT1, which has been associated with improvements in healthy ageing, whereas evidence exists that T3 may have the opposite effect. Findings suggesting that T3, T2, and their signaling pathways, such as those involving SIRT1 and AMP-activated protein kinase (AMPK), are associated with improvements in diet-induced obesity and insulin resistance emphasize the potential importance of the thyroid during ageing and in ageing-associated metabolic diseases.
authors.affiliation: Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, Caserta 81100, Italy.
authors.forename: Pieter
authors.initials: P
authors.lastname: de Lange
authors.forename: Federica
authors.initials: F
authors.lastname: Cioffi
authors.forename: Elena
authors.initials: E
authors.lastname: Silvestri
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
authors.forename: Antonia
authors.initials: A
authors.lastname: Lanni
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging; D000818:Animals; D004104:Diiodothyronines / Q000378:metabolism*; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D004104:Diiodothyronines; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; C030103:3,5-diiodothyronine; D007453:Iodide Peroxidase; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1