Background: Age‐related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age‐related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut–muscle axis. However, the effects and mechanisms of probiotics in age‐related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice.Methods: We administered LcS (1 × 10⁸ or 1 × 10⁹ CFU/mouse/day) by oral gavage to senescence‐accelerated mouse prone‐8 mice for 12 weeks (16‐ to 28‐week‐old). Sixteen‐week‐old and 28‐week‐old SMAP8 mice were included as non‐aged and aged controls, respectively. Muscle condition was evaluated using dual‐energy X‐ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme‐linked immunosorbent assay. Gas chromatography–mass spectrometry was utilized to measure the short‐chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool.Results: The LcS supplementation reduced age‐related declines in muscle mass (>94.6%, P < 0.04), strength (>66% in holding impulse and >96.3% in grip strength, P < 0.05), and mitochondrial function (P < 0.05). The concentration of short‐chain fatty acids (acetic, isobutyric, butyric, penic, and hexanoic acid) was recovered by LcS (>65.9% in the mice given high dose of LcS, P < 0.05) in the aged mice, and LcS attenuated age‐related increases in inflammation (P < 0.05) and reactive oxygen species (>89.4%, P < 0.001). The high dose of LcS supplementation was also associated with distinct microbiota composition as indicated by the separation of groups in the beta‐diversity analysis (P = 0.027). LcS supplementation altered predicted bacterial functions based on the gut microbiota. Apoptosis (P = 0.026), p53 signalling (P = 0.017), and non‐homologous end‐joining (P = 0.031) were significantly reduced, whereas DNA repair and recombination proteins (P = 0.043), RNA polymerase (P = 0.008), and aminoacyl‐tRNA biosynthesis (P = 0.003) were increased. Finally, the genera enriched by high‐dose LcS [linear discriminant analysis (LDA) score > 2.0] were positively correlated with healthy muscle and physiological condition (P < 0.05), while the genera enriched in aged control mice (LDA score > 2.0) were negatively associated with healthy muscle and physiological condition (P < 0.05).Conclusions: Lactobacillus casei Shirota represents an active modulator that regulates the onset and progression of age‐related muscle impairment potentially via the gut–muscle axis.

Sarcopenia is a common impairment in the elderly population responsible for poor outcomes later in life; it can be caused by age-related alternations. Only a few strategies have been reported to reduce sarcopenia. Lactobacillus paracasei PS23 (LPPS23) has been reported to delay some age-related disorders. Therefore, here we investigated whether LPPS23 decelerates age-related muscle loss and its underlying mechanism. Female senescence-accelerated mouse prone-8 (SAMP8) mice were divided into three groups (n=6 each): non-aging (16-week-old), control (28-week-old), and PS23 (28-week-old) groups. The control and PS23 groups were given saline and LPPS23, respectively. We evaluated the effects of LPPS23 by analyzing body weight and composition, muscle strength, protein uptake, mitochondrial function, reactive oxygen species (ROS), antioxidant enzymes, and inflammation-related cytokines. LPPS23 significantly attenuated age-related decreases of muscle mass and strength. Compared to the control group, the non-aging and PS23 groups exhibited higher mitochondrial function, IL10, antioxidant enzymes, and protein uptake. Moreover, inflammatory cytokines and ROS were lower in the non-aging and PS23 groups than the control group. Taken together, LPPS23 extenuated sarcopenia progression during aging; this effect might have been enacted by preserving the mitochondrial function via reducing age-related inflammation and ROS and by retaining protein uptake in the SAMP8 mice.

Probiotic supplements are potential therapeutic agents for age-related disorders due to their antioxidant and anti-inflammatory properties. However, the effect of probiotics on age-related brain dysfunction remains unclear. To investigate the effects of Lactobacillus paracasei PS23 (LPPS23) on the progression of age-related cognitive decline, male and female senescence-accelerated mouse prone 8 (SAMP8) mice were divided into two groups (n = 6 each): the control and PS23 groups. From the age of 16 weeks, these groups were given saline and LPPS23, respectively, because SAMP8 mice start aging rapidly after four months of age. After 12 weeks of treatment, we evaluated the effect of LPPS23 by analyzing their appearance, behavior, neural monoamines, anti-oxidative enzymes, and inflammatory cytokines. The PS23 group showed lower scores of senescence and less serious anxiety-like behaviors and memory impairment compared to the control group. The control mice also showed lower levels of neural monoamines in the striatum, hippocampus, and serum. Moreover, LPPS23 induced the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Higher levels of tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP1) and lower levels of interleukin (IL)-10 indicated that LPPS23 modulated the inflammation. Our results suggest that LPPS23 supplements could delay age-related cognitive decline, possibly by preventing oxidation and inflammation and modulating gut–brain axis communication.

Taiwanese green propolis ethanol extract (TGPE) is produced only in Taiwan and has a different composition from other types of propolis. TGPE is known for its anti-inflammation, anti-oxidation, and anti-microbial properties, but the effects and mechanisms of TGPE in the modulation of diabetes are unclear. In this study, we investigated the effects of TGPE on type 2 diabetes mellitus (T2DM) in a streptozotocin/high-fat-diet (STZ/HFD)-induced T2DM rat model. The results revealed that TGPE delayed the development and progression of T2DM and reduced the severity of β-cell failure. TGPE also attenuated inflammation and reactive oxygen species ROS in the rats. Moreover, there were higher levels of oxidant cytokines, leptin, and adiponectin in the serum of the TGPE-treated group. Unlike Brazilian propolis, TGPE promoted hepatic genes PPAR-α and CYP7A1, which were related to lipid catabolism and removal. TGPE may thus delay the progression of T2DM through anti-inflammation effects, anti-oxidation effects, and balancing lipid metabolism. It is suggested that TGPE can be a potential alternative medicine for T2DM.

Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression.