Record #185132 - GSI Repository

THYRAGE

Resetting the THYRoid axis for prevention of AGE-related diseases and co-morbidities

Coordinator	ACADEMISCH ZIEKENHUIS LEIDEN ; University of Naples Federico II ; INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES ; CNRS - Institut des Sciences Biologiques ; Imperial College of Science Technology and Medicine ; PEPSCAN THERAPEUTICS BV
Grant period	2016-01-01 - 2021-06-30
Funding body	European Union
Call number	H2020-PHC-2015-two-stage
Grant number	666869
Identifier	G:(EU-Grant)666869

Note: We hypothesize that inappropriate thyroid hormone action in target cells is a common mechanism underlying susceptibility to age-related degenerative diseases and co-morbidities. Although regulation of systemic thyroid status is well understood and underpins treatment of common thyroid disease, it is only in the last decade that the importance of local regulation of thyroid hormone action in tissue development, homeostasis and repair has been identified. During evolution, this complex temporal and cell-specific regulation has been optimized for development and reproductive fitness but NOT for ageing. Humans with their exceptional longevity are thus exposed to a prolonged period of suboptimal local thyroid hormone action. Consistent with this, thyroid status is a continuous variable within the population that is related to fracture risk, muscle mass and cognitive decline. Moreover, in healthy longevity thyroid status is characterized by thyroid stimulating hormone in the upper half of the reference range. In these studies, we will determine how local regulation of thyroid hormone action controls tissue homeostasis and repair, whilst its dysregulation is a common mechanism underlying chronic disease development during ageing. We focus on osteoporosis, osteoarthritis, neurodegeneration and sarcopenia as paradigm age-related, degenerative disorders. Using cutting-edge technology, we will (i) identify thyroid hormone dependent biomarkers for disease susceptibility in bone, cartilage, central nervous system and skeletal muscle, (ii) manipulate cell-specific thyroid hormone action in these tissues and (iii) develop cell-type specific modulators of thyroid hormone action. THYRAGE integrates cross-disciplinary expertise from clinical and basic scientists, endocrinologists, neuroscientists, gerontologists, and industry-based peptide scientists. These studies will identify and validate novel strategies for prevention and treatment of chronic age-related degenerative disease.

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Record created 2016-02-14, last modified 2023-02-14

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