ACTLIFE: is Active Life-style Enough for Health and Wellbeing in Elderly?

The first aim of this projects will be to identify the bioactive molecules and functional mechanisms that are candidates for exercise-induced health benefits through biological pathways that are largely different from those targeted by common drugs. In the view of more reliable, ecological and tailored approaches to counteract the pandemic problem of sedentary lifestyle in elderly population, the second aim of this project will be to evaluate the effectiveness of an ecological exercise intervention (EEI) in comparison to traditional exercise intervention (TEI) in sedentary older adults.

Introduction: Despite our society has developed several advances in technology and medicine, the human genetic framework is largely tailored to support the physical activity (PA) patterns of hunter-gatherer societies living 2.5 million years ago, for which food finding was obligatorily associated to PA. The energy expenditure of hunter-gatherers (1,500 kcal/day) is similar to 3h/day of moderate-to-vigorous PA (MVPA). Contrarily, technological improvements have influenced the dramatic drop in human PA levels: 1/3 of adults worldwide are currently inactive, and the endemic inactivity trend starts in early life. Indeed, sedentary behaviors in contemporary obesogenic environments trigger dysfunctions that cause chronic diseases and this phenomenon is becoming a major public health problem. Interestingly, regular PA has a profound effect on the expression of the potentials of human resilience, resulting in numerous positive adaptations and decreased risk of chronic diseases.

Protective role of exercise on cardiovascular disease risk factors: There is strong epidemiological evidence indicating that regular PA is associated with reduced rates of cardiovascular disease (CVD), hypertension, stroke, metabolic syndrome and Type 2 diabetes. Moreover, a dose-response of PA is usually observed in the general population. It is important to note, that exercise training has an improving effect on endothelial function.

The polypill-like effect of Exercise: Despite, in the last 40 years the pandemic increase of cardio-metabolic diseases has paralleled the advances in medicine, CVD remains the leading cause of death worldwide. In this complicated scenario, Wald and Law first described a combination pill for CVD prevention, which they called a "polypill". These authors claimed that CVD could be reduced by 88% and strokes by 80% if all those over 55 years of age were given a polypill containing statin, low-dose aspirin, and folic acid. This controversial and provocative approach of "medicalizing" the population is not possible and not ethical, but polypill-like benefits are achievable with a drug-free intervention, regular PA. It is worth of mention that the identification of the bioactive molecules and biological mechanisms that are candidates for exercise-induced health benefits through biological pathways that are largely different from those targeted by common drugs, is highly relevant, since it might help to improve our knowledge of the pathophysiology of the chronic diseases in the sedentary eldely population as well as to maximize the efficacy of PA interventions by implementing the best possible exercise dosage, resulting in optimal circulating levels of "health" molecules.

The exercise polypill: Skeletal-muscle fibers can produce a plethora of secreted factors, including proteins, growth factors, cytokines, with such secretory capacity increasing during active exercise, myogenesis and muscle remodeling. Muscle-derived molecules exerting either paracrine or endocrine effects are termed "myokines" and can be consider the exercise polypill.