Karan S. Rana1, Helen R. Griffiths1, Placido Navas2 and James E. Brown1*
1Aston Research Centre for Healthy Ageing & School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK
2Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, and CIBERER Instituto de Salud Carlos III, Sevilla 41023, Spain
Received: 18 August, 2014; Accepted: 20 September, 2014; Published: 22 September, 2014
Dr. James Brown, Aston Research Centre for Healthy Ageing & School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK, Tel: 01212045039; Fax: 01212043696; Email:
Rana KS, Griffiths HR, Navas P, Brown JE (2014) The Interaction between Metabolic Disease and Ageing. Glob J Obes Diabetes Metab Syndr 1(1): 007-011. DOI: 10.17352/2455-8583.000002
© 2014 Rana KS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Ageing; Metabolism; Caloric restriction; Nutrient excess; SIRT1; mTor
Two of the greatest crises that civilisation faces in the 21st century are the predicted rapid increases in the ageing population and levels of metabolic disorders such as obesity and type 2 diabetes. A growing amount of evidence now supports the notion that energy balance is a key determinant not only in metabolism but also in the process of cellular ageing. Much of genetic evidence for a metabolic activity-driven ageing process has come from model organisms such as worms and flies where inactivation of the insulin receptor signalling cascade prolongs lifespan. At its most simplistic, this poses a conundrum for ageing in humans – can reduced insulin receptor signalling really promote lifespan and does this relate to insulin resistance seen in ageing? In higher animals, caloric restriction studies have confirmed a longer lifespan when daily calorie intake is reduced to 60% of normal energy requirement. This suggests that for humans, it is energy excess which is a likely driver of metabolic ageing. Interventions that interfere with the metabolic fate of nutrients offer a potentially important target for delaying biological ageing.
In the coming decades the UK faces a dual crisis of an ageing population and increasing levels of obesity and associated disorders, including diabetes. Demographic research has confirmed that the UK and European populations are increasingly skewed towards older adults , and that this trend is likely to continue in the future. Added to this, concomitant increases in obesity  and type 2 diabetes  represent significant social, medical and economic challenges in the future.
The process of ageing negatively affects many tissues in the human body, e.g. decreasing collagen elasticity and increasing collagen deposition in fibrosis, but ageing has a particularly significant impact on those tissues associated with nutrient metabolism such as the pancreas. It is well established that the incidence of the metabolic disorder type 2 diabetes, a disease that is characterised by elevated blood glucose levels, increases with age [4,5]. This may be due to the fact that as the human body ages, peripheral tissues become less sensitive to the actions of the hormone insulin, secreted from the pancreas in response to post-prandial increases in blood glucose . The specific reasons for this age-related decrease in insulin sensitivity are not fully understood, and may reflect a failure to adapt to chronic metabolic stress. Diabetes itself is known to significantly decrease the chances of successful ageing, and notably increases the extent of functional impairment in vision, renal function and cognitive function .
Increasing evidence suggests that energy balance is central to both successful ageing and protection from metabolic disorders. The close links between these two phenomena are reviewed here.
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