Vitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to... Show moreVitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to vitamin D deficiency and that, if untreated, it can have serious health consequences. This thesis deliberates on the topics of vitamin D supplementation in older people in light of the current guidelines and on the possible additional effects of ultraviolet light beyond vitamin D synthesis on nursing home residents. We present a cross-sectional study in nursing home residents aged 70 years and over designed to evaluate the efficacy of vitamin D supplementation in achieving vitamin D sufficiency. We also discuss the different supplementation strategies for nursing home residents and community dwelling persons aged 70 years and over based on a survey administered to general practitioners and elderly care physicians in the Netherlands.In the second part we concentrate on additional effects of ultraviolet light beyond vitamin D synthesis. We describe our systematic review of literature on the effect of ultraviolet light, when applied to the skin or eyes, on mood, depression and well-being. We present also our randomized controlled trial on the effect of ultraviolet radiation compared with oral vitamin D supplementation on the well-being of nursing home residents with dementia. Further we use the data of the RCT to carry out a post-hoc analysis to compare the effect of vitamin D alone compared with ultraviolet radiation on the blood pressure of old people with dementia. Show less
Throughout the animal kingdom, species have evolved an internal time-keeping system, referred to as a 'biological clock'. This internal clock allows anticipation to profound, but largely... Show moreThroughout the animal kingdom, species have evolved an internal time-keeping system, referred to as a 'biological clock'. This internal clock allows anticipation to profound, but largely predictable, environmental day-night changes on earth. The biological clock drives 24h-rhythms in physiology and behaviour, and aligns the endogenous rhythms to the external solar day in a close temporal relationship. Being in synchrony with the environmental light-dark cycle allows the organism to cope adequately with daily changes in food availability, ambient temperature, the presence of predators, mating opportunities and/or social interactions. Additionally, the biological timing system has a major function in the regulation of seasonal rhythms, for instance in reproduction, animal migration and fur change. In order to be of functional use, the biological clock needs to be adjusted to the 24h cycle of the environment on a daily basis. The most important stimulus to regulate the synchronisation is light, which is detected via specialized eye pigments. Apart from light (photic stimulus), the biological clock is also responsive to non-photic stimuli, such as behavioural activity and pharmacological agents. The research described in this thesis examines how photic and non-photic cues modulate the activity of the biological clock. Show less
DNA is continuously exposed to exogenous and genotoxic insults including ionizing and ultraviolet radiation as well as chemical agents. DNA damage can compromise the integrity of the genome and... Show moreDNA is continuously exposed to exogenous and genotoxic insults including ionizing and ultraviolet radiation as well as chemical agents. DNA damage can compromise the integrity of the genome and have potentially deleterious effects. Ultraviolet light (UV) can induce the formation of helix distorting lesions such as 6-4 photoproducts (6-4PP) and cyclopyrimidine dimers (CPD). In humans, the nucleotide excision repair (NER) pathway is solely responsible for the repair of these lesions. A defect in NER can lead to extreme sun sensitivity and an elevated risk of developing skin cancer as observed in patients with the inherited disorder xeroderma pigmentosum. The work described in this thesis focuses on NER in human cells. Findings include: 1) UV-DDB stimulates the repair of photolesions, 2) UV-DDB binds to UV lesions independently of XPC suggesting it may have a role in chromatin priming, 3) the sealing of DNA nicks during NER are entirely on XRCC1-DNA ligase III_ complex in quiescent cells, 4) RPA couples NER mediated incision to DNA repair synthesis and ligation, 5) Arsenic induces its co-carcinogenic effects at least in part by disrupting the sealing of DNA nicks that arise during NER. Show less
Of all exogenous agents that damage genomic DNA and hence threaten its integrity, the ultraviolet B (UVB) component of sunlight is highly relevant because of its abundance. UVB induces... Show moreOf all exogenous agents that damage genomic DNA and hence threaten its integrity, the ultraviolet B (UVB) component of sunlight is highly relevant because of its abundance. UVB induces predominantly cyclobutane pyrimidine dimers and 6-4 photoproducts. In humans, these photolesions are repaired by the nucleotide excision repair (NER) system. Additionally NER removes a range of bulky, helix-distorting lesions, including chemical adducts caused by the anticancer drug cisplatin and complex hydrocarbons found in burnt food and cigarette smoke. Patients suffering from xeroderma pigmentosum, an inherited disorder caused by mutations in genes encoding NER proteins, display hypersensitivity to sunlight and a dramatically increased incidence of skin cancers. The research in this thesis concerns NER in intact human cells. Findings include: 1) the NER complex assembles on a lesion in a sequential manner, as opposed to pre-existing as a holo-complex; 2) TFIIH is not involved in the UV-induced inhibition of transcription; 3) XPA is not complexed with RPA, contradicting previous reports; 4) UV-DDB stimulates the repair of low levels of 6-4 photoproducts; and 5) pol_, pol_ and ligase I are involved in the DNA resynthesis step of NER in vivo. Show less
