Nature Communications
·
2026
·
IF 18.1
Lei Ying,Zhan Xu,Chen Chao,Liu Yuxin,Wang Ying,Liu Ping
Effective host defense against pathogens requires coordinated behavioral and immune responses, yet the mechanisms that couple epithelial sensing to these systemic defenses remain poorly understood. Here, we identify a proton-mediated gut-to-neuron signaling pathway that orchestrates host defense in C. elegans . Intestinal pathogens stimulate mechanosensitive Ca 2+ influx into intestinal epithelial cells (IECs) through the TRP channel GON-2, activating the Na + /H + exchanger NHX-6 via the calmodulin CMD-1 to drive basolateral proton release. These protons activate cholinergic motor neurons through the acid-sensing ion channel ASIC-1, enhancing cholinergic transmission to promote both pathogen avoidance and intestinal innate immunity. Notably, mouse NHE1 and ASIC1a can functionally substitute for their nematode counterparts. Together, these findings demonstrate a role for proton signaling in gut-to-neuron communication, revealing a potentially conserved mechanism that links epithelial sensing to neuroimmune defense.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2026
·
IF 5.2
Liangyong Shao,Xiaohan Zhang,Jiamei Xin,Baorui Li,Huiyong Lian,Jiao Xie,Kai Yu,Ye Zhang,Hao Wang
Silibinin had both anti-obesity and anti-aging effects. • The effects of Silibinin on obesity and aging were linked to the IIS pathway. • Network pharmacology and molecular docking verified Silibinin 's anti-obesity mechanism. Although silibinin (SIL), from milk thistle, has been reported to promise health promotion and disease treatment, the potential mechanism of SIL in improving obesity is still unknown. The fat accumulation was decreased by 78% and 49% in cellular and high glucose-induced (HGI) Caenorhabditis elegans ( C.elegans ) models. The decreased lipid droplets in both average size and quantity in the cytoplasm of the liver and EWATs were obtained by histology (hematoxylin & eosin) experiments. The promoted health effects in lifespan, stress ability, antioxidant ability, changed lipofuscin accumulation, pharyngeal pumping rate, and aging-related indexes of exercise were also confirmed. The increased expressions of daf-2, akt-1, daf-16, and skn-1 , combined with the downstream target genes of IIS-mediated mTOR signaling factors ( pha-4, hlh-30, lgg-1, and unc-51 ) and adipose-related factors ( nhr-49, fat-5, fat-6, and fat-7 ) in C. elegans were verified through the insulin/insulin-like growth factor-1 signaling pathway. SIL was proposed as a potential adjuvant remedy or nutraceutical for improving obesity and promoting health. Download: Download high-res image (146KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 20
·9912-9921
·
IF 5.396
Mohan Zhang,Shuai Chen,Yuhua Dai,Ting Duan,Yuying Xu,Xiaolin Li,Jun Yang,Xinqiang Zhu
Aspartame (ASP) and sucralose (SUC) are non-nutritive sweeteners which are widely consumed worldwide. They are considered safe for human consumption, but their effects on certain physiological aspects, such as the lifespan or health status, of the organism have not yet been studied in depth and only limited data are available in the literature. The objectives of this study were to evaluate the effects of ASP and SUC on the lifespan and health indexes using Caenorhabditis elegans (C. elegans) as a model system. Interestingly, it was shown that at the concentrations tested, ASP (0.03–3 mg mL−1) showed an increasing trend of the mean lifespan of C. elegans, with a significant increase of 27.6% compared to the control at 3 mg mL−1. Similarly, SUC (ranging from 0.03 to 10 mg mL−1) also significantly increased the mean lifespan by 20.3% and 22.3% at 0.03 and 0.3 mg mL−1, respectively. However, 10 mg mL−1 SUC had a negative effect on the lifespan, though it did not reach a statistically significant level. In addition, ASP and SUC decreased lipofuscin accumulation and transiently improved motility, indicating improved health status. Nonetheless, they had different effects on food intake and intestinal fat deposition (IFD) at different intervals of time. Taken together, our findings revealed that ASP and SUC can prolong the lifespan and improve the health status of C. elegans.
研究领域:
生物学
·
营养学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
·
2022
·
IF 13.417
Yangli Liu,Jun Zhou,Ning Zhang,Xueying Wu,Qian Zhang,Wenfeng Zhang,Xinyu Li,Ye Tian
Mitochondrial perturbations within neurons communicate stress signals to peripheral tissues, coordinating organismal-wide mitochondrial homeostasis for optimal fitness. However, the neuronal control of the systemic stress regulation remains poorly understood. Here, we identified a G-protein-coupled receptor (GPCR), SRZ-75, that couples with Gαq signaling in a pair of chemosensory ADL neurons to drive the mitochondrial unfolded protein response (UPR mt ) activation in the intestine via the release of neuropeptides in Caenorhabditis elegans. Constitutive activation of Gαq signaling in the ADL neurons is sufficient to induce the intestinal UPR mt , leading to increased stress resistance and metabolic adaptations. Ablation of ADL neurons attenuates the intestinal UPR mt activation in response to various forms of neuronal mitochondrial dysfunction. Thus, GPCR and its Gαq downstream signaling in two sensory neurons coordinate the systemic UPR mt activation, representing a previously uncharacterized, but potentially conserved, neuronal signaling for organismal-wide mitochondrial stress regulation.
研究领域:
细胞生物学
·
神经生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jia-ping Ke,Jia-Yi Li,Zi Yang,Hao-Yue Wu,Jing-Ya Yu,Yi Yang,Chen-Hui Chen,Peng Zhou,Fang Hua,Wei Wang,Fenglin Hu,Gang-Xiu Chu,Xiao-Chun Wan,Guan-Hu Bao
Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 μM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis , increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism.
研究领域:
衰老研究
·
生物化学
·
药理学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Wenning Lan,Xiaojing Zhang,Junhao Lin,Xiaolian Xiao,Junkun Chen,Shiying Sun,Guanlan Hong,Jingjing Nian,Fangrong Zhang,Yun Zhang
The increasing demand for rare earth elements (REEs) in modern applications has drawn significant attention. REEs can be introduced into the environment through REE-containing fertilizers, abandoned REE-rich equipment, and mining, persisting and impacting soil quality, nutrient cycles, and plant growth. Scientists have raised concerns about REEs entering the food chain from the environment and eventually accumulating in organisms. Decades of experimental evidence have shown that these effects include inhibited growth, impaired liver function, and alterations in children's intelligence quotients. However, there exists a paucity of research that has elucidated the metabolic-level biological impacts of REEs. In our study, Caenorhabditis elegans ( C. elegans ) was used as a model organism to investigate physiological and inherent metabolic changes under exposure to different concentrations of REEs. The diet bacteria of nematodes play a key role in their life and development. Therefore, we investigated the influence of bacterial activity on the nematodes' response to REE exposure. We observed a concentration-dependent accumulation of REEs in nematodes, which consequently led to a reduction in lifespan and alterations in body length. Exposure to a mixed solution of REEs, in comparison to a single REE solution, resulted in greater toxicity toward nematodes. The metabolic results showed that the above changes were closely related to REE-induced amino acid metabolism disorder, membrane disturbance, DNA damage, and oxidative stress. Of note, the presence of living bacteria elicits REE effects in C. elegans . These findings highlight the potential intrinsic metabolic changes occurring in nematodes under REE exposure. Our study raises awareness of the exposure risks associated with REEs, provides valuable insight into the metabolic-level biological impacts of REEs and contributes to the development of effective mitigation strategies to reduce potential risks to human health.
研究领域:
环境科学
·
毒理学
·
分子生物学
·
生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2023
·Vol. 80
·期 8
·1-18
·
IF 8
Cao Xuwen,Xie Yusu,Yang Hanwen,Sun Peiqi,Xue Beining,Garcia L. Rene,Zhang Liusuo
Dietary intake and nutrient composition regulate animal growth and development; however, the underlying mechanisms remain elusive. Our previous study has shown that either the mammalian deafness homolog gene tmc-1 or its downstream acetylcholine receptor gene eat-2 attenuates Caenorhabditis elegans development in a chemically defined food CeMM ( C. elegans maintenance medium) environment, but the underpinning mechanisms are not well-understood. Here, we found that, in CeMM food environment, for both eat-2 and tmc-1 fast-growing mutants, several fatty acid synthesis and elongation genes were highly expressed, while many fatty acid β-oxidation genes were repressed. Accordingly, dietary supplementation of individual fatty acids, such as monomethyl branch chain fatty acid C17ISO, palmitic acid and stearic acid significantly promoted wild-type animal development on CeMM, and mutations in either C17ISO synthesis gene elo-5 or elo-6 slowed the rapid growth of eat-2 mutant. Tissue-specific rescue experiments showed that elo-6 promoted animal development mainly in the intestine. Furthermore, transcriptome and metabolome analyses revealed that elo-6 /C17ISO regulation of C. elegans development may be correlated with up-regulating expression of cuticle synthetic and hedgehog signaling genes, as well as promoting biosynthesis of amino acids, amino acid derivatives and vitamins. Correspondingly, we found that amino acid derivative S-adenosylmethionine and its upstream metabolite methionine sulfoxide significantly promoted C. elegans development on CeMM. This study demonstrated that C17ISO, palmitic acid, stearic acid, S-adenosylmethionine and methionine sulfoxide inhibited or bypassed the TMC-1 and EAT-2-mediated attenuation of development via metabolic remodeling, and allowed the animals to adapt to the new nutritional niche.
研究领域:
分子生物学
·
发育生物学
·
遗传学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8
Zeng-Yang Wang,Xin-Jie Zhao,Shuo Gao,Yuan-Xin Liao,Hao-Cheng Chen,Meng-Ge Zhang,Cheng-Cheng Li,Zhi-Jie Sun,De-Li Dong
PDE4 inhibitors roflumilast and rolipram extend lifespan and improve fitness in C. elegans ; roflumilast attenuates cellular senescence in mouse embryonic fibroblasts. • Roflumilast and rolipram enhance mitochondrial function and reduce ROS levels by activating PKA signaling. • PDE4/cAMP/PKA signaling pathway-mediated anti-aging effects are conserved. Aging is driven by multiple factors such as mitochondrial dysfunction and oxidative stress, leading to various age-related diseases. Phosphodiesterase-4 (PDE4) is a subfamily of phosphodiesterases and specifically hydrolyzes cAMP. PDE4 inhibitors have been approved for the treatment of several diseases and shown to improve aging-related conditions. However, the precise effects and underlying mechanisms of PDE4 inhibitors on lifespan and cellular senescence remain unclear. Here, we report that two PDE4 inhibitors (roflumilast and rolipram) extend C . elegans lifespan and that roflumilast attenuates passage-induced cellular senescence in mouse embryonic fibroblasts (MEFs). We further demonstrate that protein kinase A (PKA) activation mediates PDE4 inhibitors’ anti-aging effects by improving mitochondrial function and alleviating oxidative stress, and that the mechanism is conserved in C. elegans and MEFs. Our findings provide evidence that PDE4 inhibitors possess anti-aging potential. Download: Download high-res image (205KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
Aging-US
·
2020
·
IF 4.831
Xin Yang,Mohan Zhang,Yuhua Dai,Yuchao Sun,Yahyah Aman,Yuying Xu,Peilin Yu,Yifan Zheng,Jun Yang,Xinqiang Zhu
Aging is the primary driver of various diseases, including common neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Currently there is no cure for AD and PD, and the development of novel drug candidates is demanding. Spermidine is a small anti-aging molecule with elimination of damaged mitochondria via the process of mitophagy identified as a molecular mechanism of action. Here, we show that spermidine inhibits memory loss in AD worms and improves behavioral performance, e.g., locomotor capacity, in a PD worm model, both via the PINK1-PDR1-dependent mitophagy pathway. Additionally, spermidine delays accelerated aging and improves healthspan in the DNA repair-deficient premature aging Werner syndrome (WS) worm model. While possible intertwined interactions between mitophagy/autophagy induction and DNA repair by spermidine are to be determined, our data support further translation of spermidine as a possible therapeutic intervention for such diseases.
研究领域:
生物学
·
医学
·
神经科学
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Chenyin Wang,Meigui Yang,Dongyao Liu,Chaogu Zheng
Summary Microbial metabolites that can modulate neurodegeneration are promising therapeutic targets. Here, we found that the short-chain fatty acid propionate protects against α-synuclein-induced neuronal death and locomotion defects in a Caenorhabditis elegans model of Parkinson’s disease (PD) through bidirectional regulation between the intestine and neurons. Both depletion of dietary vitamin B 12 , which induces propionate breakdown, and propionate supplementation suppress neurodegeneration and reverse PD-associated transcriptomic aberrations. Neuronal α-synuclein aggregation induces intestinal mitochondrial unfolded protein response (mitoUPR), which leads to reduced propionate levels that trigger transcriptional reprogramming in the intestine and cause defects in energy production. Weakened intestinal metabolism exacerbates neurodegeneration through interorgan signaling. Genetically enhancing propionate production or overexpressing metabolic regulators downstream of propionate in the intestine rescues neurodegeneration, which then relieves mitoUPR. Importantly, propionate supplementation suppresses neurodegeneration without reducing α-synuclein aggregation, demonstrating metabolic rescue of neuronal proteotoxicity downstream of protein aggregates. Our study highlights the involvement of small metabolites in the gut-brain interaction in neurodegenerative diseases.
研究领域:
神经科学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2026
·
IF 18.1
Lei Ying,Chen Chao,Zhan Xu,Xie Mingshu,Wang Ying,Li Hao,Zhang Jiale,Liu Ping
Animals integrate internal states to guide survival-critical decisions, but whether and how intestinal bacteria influence this process by interacting with host metabolic cues remains unclear. Here we show that the intestinal pathogen P. aeruginosa overrides host decision-making in fasted C. elegans by modulating central serotonin (5-HT) signaling. Fasting promotes risk-taking by activating an intestinal energy-sensing pathway that induces the chemoreceptor SRI-36 in ADF 5-HT neurons, sensitizing ADF to food odors and triggering moderate 5-HT release that drives food attraction despite risk. In contrast, intestinal P. aeruginosa reverses this strategy by activating a distinct immune-brain axis that further amplifies SRI-36 expression and ADF sensitivity, leading to excessive 5-HT release that suppresses food attraction and prioritizes safety. These findings reveal a gut-to-brain mechanism by which metabolic and immune signals converge on central 5-HT to reshape behavioral strategies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2023
·Vol. 42
·期 11
·113349-113349
·
IF 8.8
Shao Q,Wijaya CS,Wang S,Meng X,Yuan C,Ma C,Xu S
Maintaining cellular viability relies on the integrity of the plasma membrane, which must be repaired upon damage. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion is a crucial mechanism involved in membrane repair. In C. elegans epidermal cell hyp 7, syntaxin-2 (SYX-2) facilitates large membrane wound repair; however, the underlying molecular mechanism remains unclear. Here, we found that SNAP-25 protein RIC-4 and synaptobrevin protein SEC-22 are required for SYX-2 recruitment at the wound site. They interact to form a SNARE complex to promote membrane repair in vivo and fusion in vitro. Moreover, we found that SEC-22 localized in multiple intracellular compartments, including endosomes and the trans-Golgi network, which recruited to the wounds. Furthermore, inhibition of RAB-5 disrupted SEC-22 localization and prevented its interaction with SYX-2. Our findings suggest that RAB-5 facilitates the formation of the RIC-4/SEC-22/SYX-2 SNARE complex and provides valuable insights into the molecular mechanism of how cells repair large membrane wounds.
研究领域:
细胞生物学
·
分子生物学
·
发育生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）