Cholesterol plays a vital role in the human body as a precursor of steroid hormones and bile acids, in addition to providing structure to cell membranes. Whole body cholesterol metabolism is maintained by a highly coordinated balancing act between cholesterol ingestion, synthesis, absorption, and excretion. The aim of this review is to discuss how ageing interacts with these processes. Firstly, we will present an overview of cholesterol metabolism. Following this, we discuss how the biological mechanisms which underpin cholesterol metabolism are effected by ageing. Included in this discussion are lipoprotein dynamics, cholesterol absorption/synthesis and the enterohepatic circulation/synthesis of bile acids. Moreover, we discuss the role of oxidative stress in the pathological progression of atherosclerosis and also discuss how cholesterol biosynthesis is effected by both the mammalian target of rapamycin and sirtuin pathways. Next, we examine how diet and alterations to the gut microbiome can be used to mitigate the impact ageing has on cholesterol metabolism. We conclude by discussing how mathematical models of cholesterol metabolism can be used to identify therapeutic interventions.
In the UK vitamin B 12 deficiency occurs in approximately 20 % of adults aged > 65 years. This incidence is significantly higher than that among the general population. The reported incidence invariably depends on the criteria of deficiency used, and in fact estimates rise to 24 % and 46 % among free-living and institutionalised elderly respectively when methylmalonic acid is used as a marker of vitamin B 12 status.
The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.
Background: Effective communication by hospice nurses enhances symptom management for the patient, reduces family caregiver burden and distress, and potentially improves bereavement adjustment. However, research has not kept pace with the rising use of hospice by patients with cancer and thus we know little about how hospice nurses communicate. Methods: The overriding objective of this pilot study was to provide insight into these in-home visits. Hospice nurses audiorecorded their interactions over time with family caregivers and patients with cancer. The communication within these tapes was coded using Roter Interaction Analysis System (RIAS) and analyzed. Results: We found that tape recording home hospice nurse visits was feasible. RIAS was suited to capture the general content and process of the home hospice encounter and the coded interactions show the range of topics and emotions that are evident in the dialogue. Implications and future directions for research are discussed.
One of the greatest challenges in biology is to improve the understanding of the mechanisms which underpin aging and how these affect health. The need to better understand aging is amplified by demographic changes, which have caused a gradual increase in the global population of older people. Aging western populations have resulted in a rise in the prevalence of age-related pathologies. Of these diseases, cardiovascular disease is the most common underlying condition in older people. The dysregulation of lipid metabolism due to aging impinges significantly on cardiovascular health. However, the multifaceted nature of lipid metabolism and the complexities of its interaction with aging make it challenging to understand by conventional means. To address this challenge computational modeling, a key component of the systems biology paradigm is being used to study the dynamics of lipid metabolism. This mini-review briefly outlines the key regulators of lipid metabolism, their dysregulation, and how computational modeling is being used to gain an increased insight into this system.
Aging research is undergoing a paradigm shift, which has led to new and innovative methods of exploring this complex phenomenon. The systems biology approach endeavors to understand biological systems in a holistic manner, by taking account of intrinsic interactions, while also attempting to account for the impact of external inputs, such as diet. A key technique employed in systems biology is computational modeling, which involves mathematically describing and simulating the dynamics of biological systems. Although a large number of computational models have been developed in recent years, these models have focused on various discrete components of the aging process, and to date no model has succeeded in completely representing the full scope of aging. Combining existing models or developing new models may help to address this need and in so doing could help achieve an improved understanding of the intrinsic mechanisms which underpin aging.
Dietary folates have a key role to play in health, as deficiencies in the intake of these B vitamins have been implicated in a wide variety of clinical conditions. The reason for this is folates function as single carbon donors in the synthesis of methionine and nucleotides. Moreover, folates have a vital role to play in the epigenetics of mammalian cells by supplying methyl groups for DNA methylation reactions. Intriguingly, a growing body of experimental evidence suggests that DNA methylation status could be a central modulator of the ageing process. This has important health implications because the methylation status of the human genome could be used to infer age-related disease risk. Thus, it is imperative we further our understanding of the processes which underpin DNA methylation and how these intersect with folate metabolism and ageing. The biochemical and molecular mechanisms, which underpin these processes, are complex. However, computational modelling offers an ideal framework for handling this complexity. A number of computational models have been assembled over the years, but to date, no model has represented the full scope of the interaction between the folate cycle and the reactions, which governs the DNA methylation cycle. In this review, we will discuss several of the models, which have been developed to represent these systems. In addition, we will present a rationale for developing a combined model of folate metabolism and the DNA methylation cycle.
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