Stress is a central concept in biology and has now been widely used in psychological, physiological, social, and even environmental fields. However, the concept of stress was cross-utilized to refer to different elements of the stress system including stressful stimulus, stressor, stress response, and stress effect. Here, we summarized the evolution of the concept of stress and the framework of the stress system. We find although the concept of stress is developed from Selye’s “general adaptation syndrome”, it has now expanded and evolved significantly. Stress is now defined as a state of homeostasis being challenged, including both system stress and local stress. A specific stressor may potentially bring about specific local stress, while the intensity of stress beyond a threshold may commonly activate the hypothalamic-pituitary-adrenal axis and result in a systematic stress response. The framework of the stress system indicates that stress includes three types: sustress (inadequate stress), eustress (good stress), and distress (bad stress). Both sustress and distress might impair normal physiological functions and even lead to pathological conditions, while eustress might benefit health through hormesis-induced optimization of homeostasis. Therefore, an optimal stress level is essential for building biological shields to guarantee normal life processes.

Liver fibrosis is the result of sustained chronic liver injury and inflammation leading to hepatocyte cell death followed by the formation of fibrous scars, which is the hallmark of NASH and alcoholic steatohepatitis and can lead to cirrhosis, HCC, and liver failure. Although progress has been made in understanding the pathogenesis and clinical consequences of hepatic fibrosis, therapeutic strategies for this disease are limited. Preclinical studies suggest that peroxisome proliferator-activated receptor alpha plays an important role in preventing the development of liver fibrosis by activating genes involved in detoxifying lipotoxicity and toxins, transrepressing genes involved in inflammation, and inhibiting activation of hepatic stellate cells. Given the robust preclinical data, several peroxisome proliferator-activated receptor alpha agonists have been tested in clinical trials for liver fibrosis. Here, we provide an update on recent progress in understanding the mechanisms by which peroxisome proliferator-activated receptor alpha prevents fibrosis and discuss the potential of targeting PPARα for the development of antifibrotic treatments. Export

While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans (C. elegans) with a concomitant extension of a healthy lifespan as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine. Additionally, fluoxetine extended lifespan through the daf-2-sod-3 pathway in daf-16-dependent and -independent manners, and fluoxetine-induced lifespan extension was abolished in C. elegans sod-3, daf-2, and daf-16 mutants. In conclusion, these findings suggest that fluoxetine can promote health and longevity in C. elegans via the interaction of ROS and insulin signaling.

Xenophagy is a specific selective autophagy for the elimination of intracellular bacteria. Current evidence suggests that the processes for host autophagy system to recognize and eliminate invading bacteria are complex, and vary according to different pathogens. Although both ubiquitin-dependent and ubiquitin-independent autophagy exist in host to defense invading bacteria, successful pathogens have evolved diverse strategies to escape from or paralyze host autophagy system. In this review, we discuss the mechanisms of host autophagy system to recognize and eliminate intracellular pathogens and the mechanisms of different pathogens to escape from or paralyze host autophagy system, with a particular focus on the most extensively studied bacteria.

Neomangiferin (NG) can extend the lifespan and healthy life of C. elegans, and the underlying mechanism may be that bas-1 activates autophagy by regulating IIS and MAPK pathways.