Adrenergically stimulated fat utilization and ageing

Ageing is associated with a diminished ability to use fat as a fuel during exercise. Also, middle-aged subjects have a blunted ability to mobilize fat ty acids and to increase skeletal muscle fatty acid uptake and oxidation du ring intravenous beta-adrenergic stimulation, indicating that the sympathet ic nervous system may play a role in the disturbed fat utilization. The blu nted lipolytic response may be related to disturbances at the receptor leve l, eg a diminished number or agonist affinity of beta-adrenoceptors, or at the postreceptor level, eg a diminished activity of the hormone-sensitive l ipase complex. As the rates of fatty acid availability are not limiting dur ing exercise or beta-adrenergic stimulation in the elderly, the lowered ske letal muscle fat oxidation is probably related to an age-related decline in the capacity of skeletal muscle to oxidize fatty acids, Factors responsibl e for this decline may be a diminished content of oxidative enzymes, an inc reased glycolytic flux inhibiting fatty acid transport into the mitochondri a, or a diminished (possibly beta-adrenergically-mediated) activation of fa tty acid transport. It remains to be determined to what extent disturbances of fat metabolism may be related to the ageing process per se or whether t hey are secondary to age-related changes in body fat distribution and level of physical activity. Nevertheless, the impairments in sympathetically med iated lipolysis and fat oxidation may be of importance in the age-related i ncrease in adiposity and insulin resistance and may thus be one of the link s between ageing and increased prevalence of chronic diseases, such as obes ity, type 2 diabetes mellitus, and cardiovascular disease.