Fasting,CR Mimetics, HIIT exercise and Cryotherapy as Positive Aging Interventions: is Hormesis the common link? Exploring Integrated Cronofasting a new Multihormetic Healthy Aging Strategy.
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).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.Regular physical activity exerts also deep positive effects on the aging process.For these reasons exercise can be seen as the master polypill of the 21st century for the prevention of cardiovascular,neurological and aging related diseases. High-intensity interval training (HIIT), in particular, as shown in a Mayo Clic study of 2017, is “highly efficient” when it comes to reversing many age-related changes,yelding antiaging benefit down to cellular level like mitocondrial biogenesis,decrease of oxidative stress,of inflammation and improving of authophagic process.Many of these effects are the result of the activation of the same healthy aging pathways(AMPK,SIRTUIN,NADH,FOXO,NRF2 etc) involved in the antiaging benefits of CR and short fasting strategies.From freezing showers to cryotherapy camera, cold exposure is a physical stress that enhances nervous system health,improves sleep,increases stamina, decreases body fat, inflammation and improves biological markers of aging.It enhances also injury recovery,insulin sensivity and strenghtens immune sistem and detox pathways.Many of these beneficial effects of cold therapy seem, to be related to the activation of the same pathways promoted by short period of fasting and by HIIT exercise and that are expression of the hormetic effect of positive stress. Hormesis is the “what doesn’t kill you makes you stronger” type of stress,it comes from Greek hórmēsis "rapid motion, eagerness".Hormesis is any process in a cell or organism that exhibits a biphasic response to exposure to increasing amounts of a substance or condition like any kind of stress factor (physical,chemical,nutritional etc);it is a dose response phenomenon characterized by a low dose stimulation, high dose inhibition, resulting in either a J-shaped or an inverted U-shaped dose response.Such environmental factors that would seem to produce positive responses have also been termed "eustress" factors or Hormetins. In the fields of biology and medicine hormesis is defined as an adaptive response of cells and organisms to a moderate (usually intermittent) stress. Examples include ischemic preconditioning, exercise, dietary energy restriction and exposures to low doses of certain phytochemicals. Cold/heat stress,HIIT exercises,short period of fasting,some kind of superfoods,phytochemicals,CR and exercise mimetics can be seen as the most important hormetins or hormetic promoters.Mild /transient period of stress exert positive effects on mental,cardiovascular,metabolic and immune function,increasing the resistence to diabetes,cardiovascular and neurological diseases and promoting an optimizzation of general aging process.These actions are mediated by the activation of stress resistence genes,growth factors,neurotrophins, heat shock proteins.,energy and antioxidant enzymes.In this lecture is explored the integration of different hormetins like cronofasting, xenohormetins,HIIT exercise,cold therapy as a novel multihormetic integrated strategy in the promotion of successfull aging.