Fasting: From Physiology to Pathology

Abstract

Overnutrition is a risk factor for various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. Therefore, targeting overnutrition represents a simple but attractive strategy for the treatment of these increasing public health threats. Fasting as a dietary intervention for combating overnutrition has been extensively studied. Fasting has been practiced for millennia, but only recently have its roles in the molecular clock, gut microbiome, and tissue homeostasis and function emerged. Fasting can slow aging in most species and protect against various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. These centuried and unfading adventures and explorations suggest that fasting has the potential to delay aging and help prevent and treat diseases while minimizing side effects caused by chronic dietary interventions. In this review, recent animal and human studies concerning the role and underlying mechanism of fasting in physiology and pathology are summarized, the therapeutic potential of fasting is highlighted, and the combination of pharmacological intervention and fasting is discussed as a new treatment regimen for human diseases.

Circular RNAs in hepatocellular carcinoma: biogenesis, function, and pathology

“…Considering the ubiquitous m 6 A modification in annotated functional circRNAs, it is possible that the role of circRNA might be related to their tissue and developmental stage specificity. Several circRNAs displaying differential expression in specific tissues, developmental stages and subcellular locations may attribute to certain epigenetic and environmental mechanisms (Wu et al, 2019;Tang et al, 2023). In addition, recent evidence suggests an important role of certain RNA secondary structures, such as RNA G-quadruplex, in gene expression (Liu G. et al, 2020;Varshney et al, 2020;Liu G. et al, 2022;Tong et al, 2023).…”

A Hierarchical Mechanotransduction System: From Macro to Micro

“…Last but not least, deregulated mechanotransduction are implicated in human diseases; however, current studies in this field mainly focus on the role of single or a few molecules and signaling pathways. An integrated investigation on hierarchical mechanotransduction across multiple scales, as well as their implications in classical and emerging therapeutic interventions, [ 447 , 448 ] are urgently needed.…”

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

“…Caloric restriction induces vast changes in the metabolic pattern; 2 days of acute caloric restriction in healthy young male individuals substantially impact the plasma proteome and when studied with high-throughput mass spectrometry affected more than 10% of the high-abundant functional plasma proteins in all participants [5]. Several excellent recent reviews have focused on different forms of caloric restriction and the physiological changes involved [6 ▪ ,7 ▪▪ ]. Reductions of food intake normally occur diurnally during the postabsorptive state but may be extended to more than the usual sleeping hours (time-restricted eating), or may be maintained for a few or several days (Table 1); short-term almost complete fasting may be repeated weekly or monthly.…”

“…Intermittent or chronic caloric restriction may entrain peripheral circadian clocks not only in the liver, muscle, white adipose tissue but also in gut microbiota; decrease fasting-sensitive factors like circulating IGF -1 and affect appetite. In addition, caloric restriction may result in rapid shifts in the composition and function of the gut microbiome by modulating the abundance of specific species and increase the production of short-chain fatty acids [6 ▪ ]; enhance gut mucosal immune responses by modulating the number of B and T lymphocytes in Peyer's patches; change the secretion of gut hormones and inhibit the release of ghrelin and leptin [7 ▪▪ ].…”