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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.

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2015-two-stage

Coordinator

ACADEMISCH ZIEKENHUIS LEIDEN
Net EU contribution
€ 1 680 410,00
Address
Albinusdreef 2
2333 ZA Leiden
Netherlands

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Region
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (7)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
Net EU contribution
€ 386 043,75
Address
Rue Michel Ange 3
75794 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

MUSEUM NATIONAL D'HISTOIRE NATURELLE
France
Net EU contribution
€ 413 040,00
Address
Rue Cuvier 57
75005 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 1,25
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom
Net EU contribution
€ 1 410 151,25
Address
South Kensington Campus Exhibition Road
SW7 2AZ London

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Italy
Net EU contribution
€ 758 500,00
Address
Corso Umberto I, 40
80138 Napoli

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Region
Sud Campania Napoli
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
KISERLETI ORVOSTUDOMANYI KUTATOINTEZET
Hungary
Net EU contribution
€ 749 980,00
Address
Szigony Utca 43
1083 Budapest

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Region
Közép-Magyarország Budapest Budapest
Activity type
Research Organisations
Non-EU contribution
€ 0,00
PEPSCAN THERAPEUTICS BV
Netherlands
Net EU contribution
€ 545 625,00
Address
Zuidersluisweg 2
8243 RC Lelystad

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Oost-Nederland Flevoland Flevoland
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

PEPSCAN PRESTO BV
Netherlands
Net EU contribution
€ 56 250,00
Address
Zuidersluisweg 2
8243 RC Lelystad

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Oost-Nederland Flevoland Flevoland
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00