Vieillissement, exercice et immunité^{{star, open}}{star, open}Séminaire santé, sport et innovations, Bruxelles 27 et 28 mai 2005.

Aims: To describe the physiopathogenic mechanisms of the immunosenescence. Current knowledge: Aging is associated with a complex reshaping of the immune system characterized by increased inflammatory activity concomitant with decreased adaptive immunity. Immunosenescence is defined as a deterioration of the immune system. The clinical relevance is reflected by reports of increased incidence and a higher mortality rate from infections in elderly populations. Even more importantly, it has recently become clear that effects of inflammatory mediators are not restricted to the immune system as it has been recognized that inflammatory processes are central parts of the pathology in nearly all causes of morbidity in populations aged 65 + years such as atherosclerosis, type 2 diabetes, Alzheimer's Disease, pulmonary diseases, osteoporosis, and the geriatric syndrome of frailty. In accordance with this, systemic low-level inflammation (defined as 2-4 fold increases in levels of circulating cytokines) has turned out to be a strong, independent risk factor of morbidity and mortality in elderly populations [1]. TNF-α is a proinflammatory cytokine, which is also likely to be a central player in the risk related to systemic low-level inflammation as it is known to induce insulin resistance, elevated triglycerides, activation and dysfunction of the endothelium, pro-coagulation, and wasting. TNF-α production is increased in elderly people, resulting from a wide range of factors, e.g. life style factors such as obesity, smoking and diet, infections, and other co morbidities. However, TNF-α production is directly inhibited by physical exercise [2]. This mechanism is probably mediated by IL-6 because this cytokine inhibit TNF-α production and as IL-6 is released in large amounts to the circulation by contracting muscles, especially when the local glycogen content is low. Thus, IL-6 is believed to represent a so-called exercise factor by which working muscles mediate their effects on other tissues such as the liver and fat tissue in order to mobilize fuel and with health beneficial effects through an improved lipid profile, elevated insulin sensitivity, a lower blood pressure, and strong anti-inflammatory activities [2]. Accordingly, elderly people may benefit, in theory, from exercise induced anti-inflammatory activities that provide a possible, but yet rather unexplored pathway to reduce systemic low-level inflammation and TNF-α mediated pathology as healthy, elderly people maintain the ability to release IL-6 in response to exercise [3]. Consistent with this hypothesis, TNF-α protein decreased in muscles after resistance exercise for 3 months in frail, old adults [4] whereas only a few studies have explored if exercise also reduces the systemic inflammatory burden in the elderly.