In the young and healthy shoulder, cranially directed forces during abduction are counteracted by co-contraction of the rotator cuff muscles. In this way, it is prevented that the humerus moves... Show moreIn the young and healthy shoulder, cranially directed forces during abduction are counteracted by co-contraction of the rotator cuff muscles. In this way, it is prevented that the humerus moves cranially towards the acromion, thus entrapping subacromial tissues. During ageing however, shoulder tissues are subject to marked degeneration, which particularly concerns the rotator cuff muscles. This may have two consequences. First, due to reduced contribution of the upper parts of the rotator cuff to the abduction movement, the deltoid has to compensate, which results in a more cranially, instead of mediocranially directed force. Second, reduced stabilising force by the rotator cuff may jeopardise counteraction of cranial deltoid forces. These changes could lead to cranialisation of the humerus with painful compression of subacromial tissues, as observed in patients with Subacromial Pain Syndrome (SAPS). Previous studies have shown that by co-contraction of arm adductors, humeral-head depression may be accomplished, for the purpose of unloading subacromial tissues. In this thesis, we investigated the role of adductor co-contraction in the ageing asymptomatic population and in patients with SAPS. This has resulted in eight scientific publications with which the fundaments for evidence-based therapy in SAPS have been built, with as cornerstone training of adductor co-contraction. Show less
The shoulder joint is a frequent anatomic site of musculoskeletal pain. Most middle-aged adults with shoulder pain have been diagnosed with subacromial bursitis, or subacromial impingement syndrome... Show moreThe shoulder joint is a frequent anatomic site of musculoskeletal pain. Most middle-aged adults with shoulder pain have been diagnosed with subacromial bursitis, or subacromial impingement syndrome. Attrition underneath the acromion have been presumed to cause painful inflammation of subacromial tissues for years, but scientific evidence was limited. The real cause for subacromial pain is still unknown, which resulted in the diagnostic label “subacromial pain syndrome”. In this thesis, we focused on the effectiveness of acromioplasty in the treatment of patients with subacromial pain. We found no effect of acromioplasty over bursectomy alone on long-term shoulder pain and function. We also examined shoulder kinematics and muscle activation in patients with subacromial pain. We found an association between the size of rotator cuff tears as well as subacromial pain syndrome with shoulder kinematics, and described an increase in teres major muscle activity in subacromial pain syndrome. The project contributed to changed recommendations in guidelines regarding the treatment of subacromial pain syndrome. Our kinematic and biomechanical studies may create a biomechanical rationale for physiotherapeutic strategies targeted at the teres major muscle in the treatment of subacromial pain. Show less
Maintenance and repair is of key importance for the proper functioning of cells, tissues, and integrated physiology. We hypothesize that the balance between investments in growth, development, and... Show moreMaintenance and repair is of key importance for the proper functioning of cells, tissues, and integrated physiology. We hypothesize that the balance between investments in growth, development, and reproduction versus maintenance and repair is regulated by the brain. Specifically (the interplay of) hormones of the different hypothalamic-pituitary-target gland axes seem to be key regulators in constantly adjusting this balance to its optimal state. This thesis describes the associations between familial longevity and hormones of different hypothalamic-pituitary-target gland axes. In Chapter 2, the question is addressed whether circulating insulin-like growth factor 1 (IGF‐1) axis parameters associate with old age survival and functional status in nonagenarians from the LLS. In Chapter 3, we use growth hormone (GH) concentrations measured every 10 min over 24 h to derive and compare GH secretion parameters between offspring of long-lived families and their partners. In Chapter 4, we investigate the association between hypothalamic-pituitary-gonadal axis parameters and familial longevity. In Chapter 5, we use 24-h time series data of pituitary hormones to investigate how changes in the different hormonal axes are correlated with each other over time. In Chapter 6, we determine the circadian rhythm of bone turnover markers in healthy older subjects. Show less
In this thesis we aimed to get insight in how the methylome is established during development and subsequently degenerates during ageing using an integrative approach to the analysis of DNA... Show moreIn this thesis we aimed to get insight in how the methylome is established during development and subsequently degenerates during ageing using an integrative approach to the analysis of DNA methylation in conjunction with other levels of genomics data. The first two empirical chapters of this thesis describe the establishment and the maintenance of the epigenome during fetal development and in later life in multiple tissues. In the subsequent two chapters we investigated the loss of control over the methylome in blood and other tissues. Show less
Although mortality in old age has significantly decreased over the last fifty years in the developed world, there still remains a large inter-individual variability in ageing trajectories,... Show more Although mortality in old age has significantly decreased over the last fifty years in the developed world, there still remains a large inter-individual variability in ageing trajectories, morbidity and mortality. In the three parts of this thesis, we examined three interacting systems that have been identified as contributing to a slower pace of ageing, namely glucose/insulin metabolism (part I), the thyroid axis (part II), and the autonomic nervous system (part III). We found that familial longevity is associated with a stronger association of insulin parameters with microstructural brain parameters, and by higher TSH secretion, in the absence of differences in basal energy metabolism or differences in heart rate and its variability. Using specialized MRI techniques, we showed that subtle changes in microstructural brain parenchymal homogeneity in relation to insulin can be detected, even in brain tissue that appears normal on conventional MR imaging sequences. Insulin (rather than glucose), seemed to be a stronger indicator of micro- structural brain integrity in normo-glycemic older adults. Furthermore, intranasal application of insulin improved brain perfusion in parietal and occipital gray matter and in the thalamus of older adults. These results deepen our understanding of the physiological mechanisms and processes that underlie the ageing process. Show less
