Project description
Thyroid hormones: culprit for neurodegenerative disorders?
The thyroid is a vital endocrine gland with a key role in the metabolism, growth and development of the human body. Regulation of thyroid function at the systemic level is well known; yet there are unresolved aspects regarding thyroid hormone action at the cell level. The EU-funded THYRAGE project aims to investigate whether improper thyroid hormone action in target cells contributes to age-related degenerative diseases. The working hypothesis is that given their long lifespan, humans experience prolonged suboptimal thyroid hormone action, affecting bone strength, muscle mass, and cognition. Researchers will focus on osteoporosis, osteoarthritis and neurodegeneration, and look for disease biomarkers and target modulators with the goal of developing new treatments for age-related degenerative diseases.
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.
Fields of science
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesbasic medicinephysiologypathophysiology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineendocrinology
- medical and health sciencesbasic medicinephysiologyhomeostasis
Programme(s)
Topic(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
2333 ZA Leiden
Netherlands