Ageing, adipose tissue, fatty acids and inflammation

A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults

Extramitochondrial coenzyme Q10 in aging

Organisms maintain a complex relationship between the production of oxidative radicals and endogenous antioxidant levels and antioxidant enzymatic activities. Apart of its bioenergetics role in mitochondria, CoQ10 is also present in the rest of cell membranes and in plasma lipoproteins. In these structures, CoQ10 plays a key antioxidant role, preventing lipidic oxidative damage and regulating enzymatic and regulatory activities. Many years ago, two essential CoQ10-dependent dehydrogenases were characterized, cytochrome b5 reductase and NQO1. These enzymes are able to maintain a redox cycle of CoQ10 in membrane, preventing oxidative damage and maintaining other antioxidant systems depending on ascorbic acid and α-tocopherol. Recently, other CoQ10-dependent enzymes such as a mitochondrial dehydrogenase (FSP1) and a dehydrogenase associated with the outer leaf of the plasma membrane have increased the importance of CoQ10 in the prevention of oxidative damage and the regulation of apoptosis. The role of these enzymes in aging remains to be clearly determined but CR, a known prolongevity procedure, increases the activity of CoQ10-dependent dehydrogenases and prevents oxidative damage associated with aging. Then, maintenance of the activity of these extramitochondrial CoQ10-dependent activities seems to be important for aging and longevity.This work was supported by grants from the Instituto de Salud Carlos III