Impact of Ageing on Adipose, Muscle and Systemic Inflammation
试验速览
- 阶段
- 不适用
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Differences in immune cell populations (macrophages/Tcells) in adipose tissue of young versus old males
研究概览
简要总结
The accumulation and dysfunction of excess adipose (fat) tissue that occurs with ageing is associated with a number of chronic inflammatory disorders such as type 2 diabetes and cardiovascular disease but the underlying mechanisms are not understood.
详细描述
Adipose tissue is a highly dynamic organ that produces a wide array of adipokines which can affect the function of other tissues throughout the body. The physiology of adipose tissue is a relatively new and exciting area of research and researchers are learning more about its complexity, in particular the way in which adipose tissue plays a dynamic and active role in various normal and pathological processes. Comparatively little is known about the changes that occur within adipose tissue over the natural course of ageing - and adipose dysfunction could play a role in ageing-related chronic systemic inflammatory diseases such as type 2 diabetes and cardiovascular disease.
In this study, the investigators would like to investigate inflammatory and metabolic changes that occur within adipose tissue with ageing. the investigators would also like to examine whether age-related changes in adipose tissue are specific to this particular tissue type by comparing adipose-resident immune cell populations and measures of inflammation and metabolism to those in muscle tissue and blood.
By exploring the immune dysfunction that occurs with ageing in adipose tissue and relating them to inflammatory and metabolic differences in muscle and blood, this work may potentially reveal causal mechanisms in the development of ageing-related chronic inflammatory diseases and ultimately lead to the development of better treatment/management strategies.
BACKGROUND Adipose tissue is sizeable endocrine organ and is highly dynamic, producing a wide array of adipokines which can affect a range of physiological processes including regulation of appetite, energy expenditure, insulin sensitivity, inflammation, endocrine and reproductive systems and bone metabolism. Ageing is a process that is associated with adipose tissue accumulation, changes in adipose tissue distribution and its dysfunction which in turn are linked to the development of chronic inflammatory disorders such as type 2 diabetes and cardiovascular disease.
Adipose tissue inflammation may be key Adipose tissue consists not only of adipocytes, but also many other cell types including endothelial cells, preadipocytes, immune cells such as macrophages and lymphocytes such that adipocytes themselves may only represent 60-70 % cell numbers in adipose tissue. Research from over the last decade or so suggests that the presence of immune cells within the adipose tissue itself are important in regulating both local and systemic inflammation/production of adipokines. For example, adipose tissue macrophages contribute the majority of the pro-inflammatory cytokine TNFα and ~50% IL6 secreted by adipose tissue, which show increased secretion with adipose tissue dysfunction and are implicated in the development of chronic inflammatory disorders. Changes in adipose resident immune cells have been relatively well studied in obesity but there are comparatively few studies in humans examining changes in immune cell populations and their potential impact on adipose tissue inflammation in the context of ageing. Given the time-course of adipose tissue accumulation in obesity compared to ageing, there is the potential for differences in the underlying mechanisms of adipose tissue dysfunction to occur.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Aged between 20-35 years (Group 1) or 65-85 years (Group 2)
- •Fat mass index based on DEXA between 4-8 kg/m2
- •Weight stable for more than 3 months (no change in weight +/- 3%)
- •Physical Activity Level (PAL) between 1.4 and 1.9
- •Non-smoker
排除标准
- •Any chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders
- •Individuals who consume on a daily basis any analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription
- •Taking any medications that may influence lipid or carbohydrate metabolism or immune system function
- •Individuals with a known negative reaction to lidocaine anaesthetic
- •Participation in heavy resistance training
结局指标
主要结局
Differences in immune cell populations (macrophages/Tcells) in adipose tissue of young versus old males
时间窗: through to study completion, an average of 14 months
次要结局
- the impact of ageing on metabolic and inflammatory protein secretions (into culture media) from adipose tissue(through to study completion, an average of 14 months)
- differences in immune cell populations in muscle tissue and blood compared to adipose tissue from the same individuals and the impact of ageing on immune cell populations in muscle tissue.(through to study completion, an average of 14 months)
- the impact of ageing on mRNA expression of other key metabolic and inflammatory genes in muscle tissue.(through to study completion, an average of 14 months)
- the impact of ageing on mRNA expression of key metabolic and inflammatory genes in adipose tissue.(through to study completion, an average of 14 months)
- activation/inhibition of e.g. insulin stimulated pathways in adipose and muscle tissues (for example assessment of Akt/IRS1 phosphorylation by western blot analysis).(through to study completion, an average of 14 months)
研究者
William Trim
Ph.D. Student
University of Bath