Fasting helps nutrient sensing systems in clocking the metabolism

Abstract

Mankind is predisposed to metabolic syndromes (MetS) by its modern lifestyle. After middle age, metabolic homeostasis (MetH) consistently declines. Besides age-related pathophysiological changes, such as decline in tissue coordination and function, modifiable lifestyle factors also predispose to aging, causing disease conditions. Lifestyle choices such as erratic eating habits, reduced physical activity, smoking, alcohol intake, and erratic sleep patterns increase the risk of metabolic syndromes. These modifiable lifestyle factors operate through circadian rhythm disruption. Circadian rhythms, at the cellular level, are the gene networks with transcriptional and translational feedback loops that drive the rhythmic expression of physiological processes, aligning intracellular metabolism and organismal immunometabolism. Further, nutrient sensing systems (NSS) mediates the alignment of metabolic pathways, being central in aging control mechanisms. Recent research has shown circadian oscillations of the mammalian target of rapamycin (mTOR) complex function, as an important NSS intermediate. Autophagy stimulates NSS, including mTOR, IGF, AMPK and sirtuins, thereby preventing the negative effects of aging. The potential of intermittent fasting as a circadian health regimen and its role in promoting autophagy is highlighted in this review. It is suggested that the improvement of longevity through sustained adherence to intermittent fasting in humans, also depends on individual compliance. Therefore, global studies are needed to enhance the current understanding of the molecular underpinnings of intermittent fasting on autophagy, inflammasomes, and senescence in humans.

Keywords: Metabolic homeostasis, nutrient sensing system, intermittent fasting, mTOR, aging, lifestyle, time restricted feeding