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

Objective

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.

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis

Call for proposal

H2020-PHC-2015-two-stage
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Funding Scheme

RIA - Research and Innovation action

Coordinator

ACADEMISCH ZIEKENHUIS LEIDEN
Address
Albinusdreef 2
2333 ZA Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 680 410

Participants (5)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 799 083,75
Address
Rue Michel Ange 3
75794 Paris
Activity type
Research Organisations
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom
EU contribution
€ 1 410 151,25
Address
South Kensington Campus Exhibition Road
SW7 2AZ London
Activity type
Higher or Secondary Education Establishments
UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Italy
EU contribution
€ 758 500
Address
Corso Umberto I, 40
80138 Napoli
Activity type
Higher or Secondary Education Establishments
KIRSERLETI ORVOSTUDOMANYI KUTATOINTEZET
Hungary
EU contribution
€ 749 980
Address
Szigony Utca 43
1083 Budapest
Activity type
Research Organisations
PEPSCAN THERAPEUTICS BV
Netherlands
EU contribution
€ 601 875
Address
Zuidersluisweg 2
8243 RC Lelystad
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)