It is estimated that somewhere between 34 and 61 million people in the US are obese and in much of the developing world incidence is increasing by about 1% per year. Obesity increases the likelihood of death from all causes by 20%, and more specifically death from coronary artery disease and stroke are increased by 25% and 10% respectively. In addition to these diseases, obese patients suffer an increased incidence of arthritis. It is of note that most of the conditions associated with obesity are also associated with aging. In developed countries, there is a general increase in body weight and body mass index with age, until approximately 60 years of age. In addition, the proportion of intra-abdominal fat, which is related to increased morbidity and mortality, progressively increases with age. Targeting weight loss in the elderly can therefore reduce morbidity from arthritis, and also cardiovascular risk factors. The identification of causative links between the natural aging process and obesity could therefore be of considerable importance. Recent data emerging from the VA in Florida identifying leptin as a possible causative factor of age-related obesity is therefore particularly interesting. Leptin has gained considerable interest recently as it inhibits food intake, reduces body weight and stimulates energy expenditure (see our recent dossier "Targeting links between obesity and diabetes" - click here for access). Since obese humans generally have elevated leptin levels, it has been suggested that leptin resistance develops in obesity. It has now been reported that certain strains of rats that mimic age-related obesity also display increased leptin levels. Following both peripheral and central leptin administration, the decrease in food intake and the increase in energy expenditure are blunted in the older obese rats. These authors further demonstrate an inability of leptin to activate STAT3 phosphorylation and it's signal transduction pathway in elderly rats. This appears to result in altered regulation of neuropeptide Y which plays a crucial role in feeding. Targeting this failure of leptin to phosphorylate STAT3 may therefore represent a novel approach to age-related obesity.