NOT JUST CALORIC RESTRICTION: A COMPLEX APPROACH TO PROLONG LIFESPAN AND IMPROVE QUALITY OF LIFE

Aging is an urgent healthcare issue in view of the rapid growth of the proportion of older persons. Searching for reliable aging biomarkers and prolonging lifespan are increasingly important scientific directions. Experimental gerontology helps to explore fundamental facts which are not always applicable in clinical scenarios. As an example, caloric restriction is one of the key interventions that prolongs laboratory animals’ lifespan and ameliorates some, but not all, aging biomarkers in humans. Consequences of overeating such as obesity, insulin resistance, type 2 diabetes, and metabolic syndrome are taking their toll with aging, making caloric restriction a hot topic in gerontology and geriatrics. Nevertheless, caloric restriction is not widely applicable in view of poor adherence to and limitations of strict diets. Drugs mimicking caloric restrictions, the so-called caloric restriction mimetics, are developed to overcome these limitations. Caloric restriction alone is not a panacea since metabolic pathways are complex and not responsive to a single intervention. Fasting and exercising are additional options for reducing effects of excessive intake of calories. Arguably, physical activity significantly improves the quality of life at old age and delays the onset of overt insulin resistance and associated diseases. Thus, developing optimal fasting and exercising schemes is becoming increasingly important. Such interventions are confounded by a number of factors, including circadian and other biorhythms and baseline metabolic activity. It is justifiable to test fasting and exercising in experimental animals to reveal numerous confounding factors. A hypothesis in this article points to the role of complex interventions such as moderate and balanced diet, intermittent fasting, and physical exercise adjusted to circadian rhythms for prolonging life and improving quality of life. The hypothesis may shed light on fundamental mechanisms of aging and perspectives of anti-aging drug therapies.