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Congresso Internazionale di Medicina Antiaging-Monaco 04/018-Integrated Chronofasting,Exercise and Positive Aging: is BDNF the key?

Integrated Chronofasting,Exercise and Positive Aging: is BDNF the key?

A growing body of evidence indicates that short fasting periods and intermittent/periodic fasting regimens in particular can trigger similar biological pathways as caloric restriction in the promotion of healthy aging.Different dietary regimens are proposed by fasting strategies world scientists: (i) intermittent energy restriction (IER), which involves eliminating (fasting) or greatly reducing (e.g., 500 calories per day) daily intake food/caloric beverage intake intermittently,for example 2 d/wk with intervening periods of normal food intake, on a recurring basis;(ii) time-restricted feeding (TRF), which involves limiting daily intake of food and caloric beverages to a 4- to 8-h time window;(iii) Short term (ST) and prolonged periodic fasting (PF) to refer to IF with ciclical straight days of fasting or fasting mimicking diets lasting< 3 days (ST) to more days (3 or more )(PF).In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss (preserving muscle mass)and improvements in multiple health indicators including insulin-leptin resistance,adiponectin level, and reductions in risk factors for cardiometabolic  diseases; we find also positive promising reports in the health and aging related biomarkers like oxidative stress,glycation and inflammation in some TRF studies(Ramadam and resistance-trained males studies).

The cellular and molecular mechanisms by which IF, ST,PF and TRF improve health and counteract disease processes involve adaptive cellular responses(generated by a hormetic effect) that reduce oxidative damage and inflammation, optimize energy metabolism, enhance mitochondrial health, DNA repair and autophagy and boosts cellular protection.PF also promotes stem cell-based regeneration while TRF produces its positive actions also through the optimizzation of microbiota composition,balance and its biological rhytms.

Other effects are mediated by the antinflammatory,antioxidant, vagotonic actions exerted by the body ketones produced during longher period of fasting or when shorter fasting times are integrated by a ketogenic diet.Many beneficial health effects of ketones are also mediated by their promoting actions on the release of the neuro-metabolic trophin named  BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) by the neurons which exerts both neurotrophic  and positive cardiometabolic  ed healthy aging effects.

Physical inactivity in contemporary obesogenic environments(overnutrition combined with high caloric-multimeals diet) initiates maladaptations that cause chronic disease and is becoming a major public health problem . In contrast, regular  physical activity(PA) has a profound effect on the expression of a substantial proportion of our genome , which has been selected for optimizing aerobic metabolism to conserve energy in an environment of food scarcity  resulting in numerous beneficial adaptations and decreased risk of chronic diseases, like cardiometabolic diseases(stroke,heart attack,diabetes,obesity,metabolic syndrome,dementia and cancer,so named Diseasome of physical inactivity. Exercise biology is complex and it involves various metabolic and molecular changes that translate into changes in substrate utilization, enzyme activation, and alternatively, improvement in exercise performance. Besides the effect of exercise on muscle metabolism, it has recently been discovered that contracting muscle can induce secretion of molecules called myokines. The existence of myokines has enhanced our understanding of how muscles communicate with other organs such as adipose tissue, liver, bone, and brain to exert beneficial effects of exercise at the whole body level.In the past few decades, a number of myokines have been discovered, such as interleukin-6, irisin, myostatin, interleukin-15,  β-aminoisobutyric acid and BDNF.

In this review are explored the positive cardiometabolic,neurologic and  general health actions of this neuro-metabolic trophin that is produced by muscle also during physical activity and its  intracrine beneficial effects on glucose and fatty acids metabolism(AMPK pathway activation) and paracrine actions(insulin and leptin sensivity,adiponectin production and inflammation modulation).Exercise activates also the production of BDNF at hyppocampal and hypothalamic level through the action of the myokine Irisin on its gene expression.Central and peripheral actions effects of BDNF seem to be one of the keys of the beneficial effects of short period of fasting and of exercise in the prevention of aging and aging related diseases.

In this review, the multilevel positive effects of BDNF are showed with a particular focus on the lifestyle, nutritional and therapeutic strategies finalized to the optimizzation of the production of this precious neuro-cardio-metabolic and healthy aging trophin.

02 Giugno 2018