Specific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue... Show moreSpecific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue maintenance are an important common denominator that may lie in between specific hallmarks of ageing (i.e. damage and responses to damage) and their ultimate (patho)physiological consequences (i.e. functional decline and age-related disease). As a first step towards verifying or falsifying this hypothesis, it will be important to measure biomarkers of tissue maintenance in future studies in different study populations. The main aim of the current paper is to discuss potential biomarkers of tissue maintenance that could be used in such future studies. Among the many tissues that could have been chosen to explore our hypothesis, to keep the paper manageable, we chose to focus on a selected number of tissues, namely bone, cartilage, muscle, and the brain, which are important for mobility and cognition and affected in several common age-related diseases, including osteoporosis, osteoarthritis, sarcopenia, and neurodegenerative diseases. Furthermore, we discuss the advantages and limitations of potential biomarkers for use in (pre)clinical studies. The proposed biomarkers should be validated in future research, for example by measuring these in humans with different rates of ageing. Show less
Osteoarthritis (OA) is an age related disorder of the joints characterized by pain, crepitus, and stiffness resulting in decreased mobility. Pathophysiology consists of cartilage degeneration and... Show moreOsteoarthritis (OA) is an age related disorder of the joints characterized by pain, crepitus, and stiffness resulting in decreased mobility. Pathophysiology consists of cartilage degeneration and bone remodeling, however, knowledge of OA etiology is still limited. Due to the growing population of elderly, OA prevalence rapidly increases. The fact that no reliable clinical markers are available for diagnosis, monitoring and progression is a major impediment in OA disease management and incurs high costs in drug development and clinical trials. Molecular markers were studied in OA affected cartilage compared to unaffected cartilage of the same joint (chapter 2) and in blood of OA patients (chapter 3). Perturbation of the application of traditional biochemical markers sCOMP and uCTX2 in the clinic due to genetic factors that, independent of OA, affect innate levels was investigated (chapter 4). Furthermore, we have tried to go beyond the results of molecular epidemiological studies to increase insights into underlying mechanisms (chapter 6 & 7). This shows how functional genomics can be achieved by combining genetic and functional data and will facilitate translation of knowledge of genetic variants to the needs of OA patients and thus to application in the clinic. Show less
