In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This review summarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To further understand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventions that can be used in future exercise-related studies. PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treating various diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity [Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters: one that limited publication dates to "in 10 years" and one that sorted the results as "best match". Then we grouped the commonly used exercise methods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseases and organ functions in 8 different systems. A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exercise interventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascular system (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and the system related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntary wheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, most of them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless of the exercise method used, although some diseases showed the best remission effects when a specific method was used. Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exercise interventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention compliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exercise interventions in humans.

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.

Inter-organ crosstalk has gained increasing attention in recent times; however, the underlying mechanisms remain unclear. In this study, we elucidate an endocrine pathway that is regulated by skeletal muscle interferon regulatory factor (IRF) 4, which manipulates liver pathology. Skeletal muscle specific IRF4 knockout (F4MKO) mice exhibited ameliorated hepatic steatosis, inflammation, and fibrosis, without changes in body weight, when put on a nonalcoholic steatohepatitis (NASH) diet. Proteomics analysis results suggested that follistatin-like protein 1 (FSTL1) may constitute a link between muscles and the liver. Dual luciferase assays showed that IRF4 can transcriptionally regulate FSTL1. Further, inducing FSTL1 expression in the muscles of F4MKO mice is sufficient to restore liver pathology. In addition, co-culture experiments confirmed that FSTL1 plays a distinct role in various liver cell types via different receptors. Finally, we observed that the serum FSTL1 level is positively correlated with NASH progression in humans. These data indicate a signaling pathway involving IRF4-FSTL1-DIP2A/CD14, that links skeletal muscle cells to the liver in the pathogenesis of NASH.

Poly(ADP-ribose) polymerase-1 (PARP1) has been reported to play an important role in longevity. Here, we showed that the knockdown of the PARP1 extended the lifespan of Drosophila , with particular emphasis on the skeletal muscle. The muscle-specific mutant Drosophila exhibited resistance to starvation and oxidative stress, as well as an increased ability to climb, with enhanced mitochondrial biogenesis and activity at an older age. Mechanistically, the inhibition of PARP1 increases the activity of AMP-activated protein kinase alpha (AMPKα) and mitochondrial turnover. PARP1 could interact with AMPKα and then regulate it via poly(ADP ribosyl)ation (PARylation) at residues E155 and E195. Double knockdown of PARP1 and AMPKα, specifically in muscle, could counteract the effects of PARP1 inhibition in Drosophila . Finally, we showed that increasing lifespan via maintaining mitochondrial network homeostasis required intact PTEN induced kinase 1 (PINK1). Taken together, these data indicate that the interplay between PARP1 and AMPKα can manipulate mitochondrial turnover, and be targeted to promote longevity.