Aging in humans is associated with alterations in body fat distribution and a parallel gradual increase in the prevalence of atherosclerotic cardiovascular disease, as well as mortality of all causes. Because of nutrient cost, availability, and the sedentary life-style, half of the western world population has fat mass in excess of 30% of the body weight that weighs 3-4 times more than the fat mass of lean subjects. Recent discoveries of various hormones, cytokines and complement factors secreted by adipose cells opened a new avenue of research, looking at the role of these fat derived peptides in different conditions. We will focus here on the potential role of fat tissue in different physiological and physiopathological conditions associated with age-related metabolism and risk factors for diseases. We will also exemplify how body fat capacity, distribution and function can be directly linked, and may play a central role in energy metabolism and homeostasis, atherosclerosis, and possibly in the defense against cancer. We hypothesize that biological pathways involved in nutrient regulation in fat tissue may be important in inducing longevity in calorie restricted animals.