Ageing and metabolism: is brown fat the key?
The past decade has seen epidemiologists frequently predict two phenomena that loom darkly over the future of our society: ageing and obesity. The challenge of an increasingly old and overweight society almost certainly comes packed with grave costs in economic, health and social terms. It is therefore imperative that as scientists we study the biological basis of both ageing and obesity to provide a much fuller understanding of these two seemingly separate entities. But just how separate are they? And can scientists working in two seemingly distinct fields actually be looking at the same processes from different angles? Previous research has shown that energy balance, a dysregulation of which is central to obesity, is closely linked to the ageing process. Studies have repeatedly shown that the factors that most often correlate with telomere length in humans (outside of smoking) are metabolic parameters, including BMI, fasting blood glucose and insulin levels. Equally, many of the molecular signalling pathways that are known to be involved in cellular ageing, including insulin/IGF-1, mTor and oestrogen are also involved in maintaining a healthy metabolism. It appears that the two processes share common themes. This notion gained a significant boost recently when a paper was published in Cell Metabolism on the subject of PTEN. PTEN (phosphatase and tensin homolog) is a tumour suppressor gene that is involved in cell cycle regulation and also inhibits AKT signalling. This recent publication has shown that PTEN plays a pivotal role in both ageing and metabolism. Ortega-Molina et al showed that a moderate systemic increase in PTEN activity in mice significantly extended lifespan and protected from metabolic damage. This fascinatingly occurred alongside an increase in brown adipose tissue function. Brown adipose tissue is a specialised tissue, able to burn ATP off as heat via its high levels of uncoupling protein 1 expression. What this research clearly shows is that by regulating the energy balance of an organism, you can also regulate lifespan. Nothing new you might think, plenty of caloric restriction work has shown this before. What is really interesting about this study is the brown adipose tissue angle. Until recently it was thought that adult humans had no brown adipose tissue, a notion that has been elegantly refuted by several radioactive imaging studies. If, as this recent paper purports, brown adipose tissue activity can be pharmacologically regulated by PTEN activators we might have a therapeutic avenue which in future can be used to target both metabolic disorder and age related decline. Source: Cell Metabolism, Volume 15, Issue 3, 382-394, 7 March 2012. Source: Cell Metabolism, Volume 15, Issue 3, 382-394, 7 March 2012.