RESUMEN
Ageing and fertility are intertwined. Germline loss extends the lifespan in various organisms, termed gonadal longevity. However, the original longevity signal from the somatic gonad remains poorly understood. Here, we focused on the interaction between germline stem cells (GSCs) and their niche, the distal tip cells (DTCs), to explore the barely known longevity signal from the somatic gonad in C. elegans. We found that removing germline disrupts the cell adhesions between GSC and DTC, causing a significant transcriptomic change in DTC through hmp-2/ß-catenin and two GATA transcription factors, elt-3 and pqm-1 in this niche cell. Inhibiting elt-3 and pqm-1 in DTC suppresses gonadal longevity. Moreover, we further identified the TGF-ß ligand, tig-2, as the cytokine from DTC upon the loss of germline, which evokes the downstream gonadal longevity signalling throughout the body. Our findings thus reveal the source of the longevity signalling in response to germline removal, highlighting the stem cell niche as a critical signalling hub in ageing.
RESUMEN
Ageing is a complex process with common and distinct features across tissues. Unveiling the underlying processes driving ageing in individual tissues is indispensable to decipher the mechanisms of organismal longevity. Caenorhabditis elegans is a well-established model organism that has spearheaded ageing research with the discovery of numerous genetic pathways controlling its lifespan. However, it remains challenging to dissect the ageing of worm tissues due to the limited description of tissue pathology and access to tissue-specific molecular changes during ageing. In this study, we isolated cells from five major tissues in young and old worms and profiled the age-induced transcriptomic changes within these tissues. We observed a striking diversity of ageing across tissues and identified different sets of longevity regulators therein. In addition, we found novel tissue-specific factors, including irx-1 and myrf-2, which control the integrity of the intestinal barrier and sarcomere structure during ageing respectively. This study demonstrates the complexity of ageing across worm tissues and highlights the power of tissue-specific transcriptomic profiling during ageing, which can serve as a resource to the field.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Longevidad/genética , TranscriptomaRESUMEN
Dietary restriction (DR) is known to have a potent and conserved longevity effect, yet its underlying molecular mechanisms remain elusive. DR modulates signaling pathways in response to nutrient status, a process that also regulates animal development. Here, we show that the suppression of Wnt signaling, a key pathway controlling development, is required for DR-induced longevity in Caenorhabditis elegans We find that DR induces the expression of mir-235, which inhibits cwn-1/WNT4 expression by binding to the 3'-UTR The "switch-on" of mir-235 by DR occurs at the onset of adulthood, thereby minimizing potential disruptions in development. Our results therefore implicate that DR controls the adult lifespan by using a temporal microRNA switch to modulate Wnt signaling.
Asunto(s)
Longevidad/genética , MicroARNs/genética , Proteínas Wnt/genética , Vía de Señalización Wnt/genética , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Restricción Calórica/métodosRESUMEN
OBJECTIVE: Forgiveness Therapy is proposed as a novel approach to rehabilitation for men in a maximum-security correctional institution to alleviate psychological compromises. METHOD: In a two-tiered study, volunteer participants within a correctional institution (N = 103) were asked to report past experiences of abuse and unjust treatment prior to their first crime and were measured on anger, anxiety, depression, hope and forgiveness. Twenty four of the most clinically compromised participants were selected from this initial assessment, with pairs first matched on certain characteristics and then randomly assigned to either experimental or control group interventions followed by a cross-over design (N = 9 in each group at the study's end). Experimental participants received 24 weeks of Forgiveness Therapy. Control group participants received 24 weeks of an alternative treatment followed by Forgiveness Therapy. Dependent variables included anger, anxiety, depression, forgiveness, hope, self-esteem and empathy. RESULTS: Ninety percent of 103 participants reported moderate to severe abuse in childhood or adolescence. Data showed an inverse relationship between forgiveness and anger, anxiety and depression. In the Forgiveness Therapy, anger, anxiety, depression, empathy and forgiveness were statistically significant favouring both experimental groups. These results remained at the 6-month follow-up. CONCLUSIONS: Forgiveness Therapy is shown to be effective for correctional rehabilitation in healing clinical psychological compromise and in promoting positive psychological well-being in men within a maximum-security facility.
Asunto(s)
Perdón , Adolescente , Ira , Ansiedad , Niño , Humanos , Masculino , AutoimagenRESUMEN
The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development, whether and how developmental programs control the timing of nutritional responses remain barely known. Here, we report that a developmental timing regulator, BLMP-1/BLIMP1, governs the temporal response to dietary restriction (DR). At the end of larval development, BLMP-1 is induced and interacts with DR-activated PHA-4/FOXA, a key transcription factor responding to the reduced nutrition. By integrating temporal and nutritional signaling, the DR response regulates many development-related genes, including gska-3/GSK3ß, through BLMP-1-PHA-4 at the onset of adulthood. Upon DR, a precocious activation of BLMP-1 in early larval stages impairs neuronal development through gska-3, whereas the increase of gska-3 by BLMP-1-PHA-4 at the last larval stage suppresses WNT signaling in adulthood for DR-induced longevity. Our findings reveal a temporal checkpoint of the DR response that protects larval development and promotes adult health.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Restricción Calórica , Regulación de la Expresión Génica , Longevidad/genética , Factores de Transcripción/metabolismo , Vía de Señalización WntRESUMEN
Ageing is co-regulated by genetic and environmental factors. Life on earth lives and evolves in a mild geomagnetic field. Yet, the biological effects of a moderate magnetic field on ageing and the underlying genetic mechanisms remain barely unknown. Here, we report that a moderate static magnetic field (SMF) extends the lifespan of Caenorhabditis elegans, a well-established model organism in ageing research. Consistently, the SMF-treated worms show improved motility and mitochondrial function when aged. We identified from the transcriptomic changes upon SMF treatment that the upregulation of three cytochrome P450 genes are required for SMF-induced longevity. Our findings thus reveal that proper SMF treatment could promote longevity through the well-conserved cytochrome P450 enzymes.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/fisiología , Proteínas de Caenorhabditis elegans/genética , Sistema Enzimático del Citocromo P-450/genética , Longevidad/genética , Campos MagnéticosRESUMEN
Fruit wine has certain health care functions, but fruit wine made from a single fruit or vegetable does not have a good enough color, flavor or nutrient composition. Therefore, this study used fresh carrot (Daucus carota subsp. sativus) and pomegranate (Punica granatum) as raw materials to explore the brewing process of carrot and pomegranate compound wine. The fermentation technology of the composite carrot and pomegranate wine was optimized by a single-factor experiment and Box-Behnken design (BBD), which provided a theoretical foundation for the fermentation of this wine. As per the results, the alcohol content of this composite carrot and pomegranate wine was 12.35% vol. under the optimum fermentation conditions of 28 °C initial temperature, 24% initial sugar content, and with the addition of 64 mg L-1 sulfur dioxide (SO2). In the fermented fruit and vegetable wine, a total of 30 aroma components were detected; 21 composites (such as bornyl acetate, caryophyllene and 3-(2-nitrophenylmethyl)-2-thiazolidinone) were newly generated. The relative content of alcohol flavor composites (such as propionic acid 2-methyl-3-hydroxy-2,2,4-trimethylpentan-1-ol, 2-methyl-2-ethyl-3-hydroxycyclohexyl propanoate and terpinene-4-ol) showed an upward trend, and the relative content of alkene components increased significantly after fermentation. The findings of this study provide an experimental foundation for optimizing fermentation technology and for improving the product quality of composite carrot and pomegranate wine.
RESUMEN
Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19/RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19/RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing.
Asunto(s)
Envejecimiento , Caenorhabditis elegans/metabolismo , Cilios/metabolismo , Flagelos/metabolismo , Células Receptoras Sensoriales/fisiología , Transducción de Señal/fisiología , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Animales Modificados Genéticamente , Transporte Biológico , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Longevidad/genética , Percepción/fisiología , Interferencia de ARN , Factor Regulador X1/genética , Factor Regulador X1/metabolismo , Células Receptoras Sensoriales/metabolismo , Transducción de Señal/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Religiosity is important for religious people to maintain their subjective well-being (SWB). We propose a dual-path effect hypothesis to explore different working mechanisms of religious faith and practice on benefiting people's SWB. Religious faith can promote SWB mainly via an intrinsic meaning-making path although religious practice can promote SWB via both an intrinsic meaning-making path and an extrinsic capital-accumulating path. If the dual-path effect hypothesis stands, then the role of religious practice in influencing SWB should be partly substituted by good economic status, but the role of religious faith should not. Then, only the effect of religious practice would be moderated by wealth. Results show that people's individual income and national GDP have significant moderating effects on the relationship between religious practice and SWB, but they had no moderating effect on the association between religious faith and SWB, indicating wealth could be an alternative source of accumulating capital and social resources between religious practice and SWB. Results provide important evidence for the dual-path effect hypothesis. The findings uniquely contribute to the literature of religiosity, SWB, and their connections with wealth. Implications for future research are also discussed.
RESUMEN
Ferroptosis, implicated in several diseases, is a new form of programmed and nonapoptotic cell death triggered by iron-dependent lipid peroxidation after inactivation of the cystine/glutamate antiporter system xc-, which is composed of solute carrier family 7 membrane 11 (SLC7A11) and solute carrier family 3 membrane 2 (SLC3A2). Therefore, inducing ferroptosis through inhibiting the cystine/glutamate antiporter system xc- may be an effective way to treat cancer. In previous screening tests, we found that the benzopyran derivative 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) significantly inhibited the viability of colorectal cancer cells. However, the impact of IMCA on ferroptosis remains unknown. Hence, this study investigated the effect of IMCA on ferroptosis and elucidated the underlying molecular mechanism. Results showed that IMCA significantly inhibited the cell viability of colorectal cancer cells in vitro and inhibited tumor growth with negligible organ toxicity in vivo. Further studies showed that IMCA significantly induced the ferroptosis of colorectal cancer cells. Mechanistically, IMCA downregulated the expression of SLC7A11 and decreased the contents of cysteine and glutathione, which resulted in reactive oxygen species accumulation and ferroptosis. Furthermore, overexpression of SLC7A11 significantly attenuated the ferroptosis caused by IMCA. In addition, IMCA regulated the activity of the AMPK/mTOR/p70S6k signaling pathway, which is related to the activity of SLC7A11 and ferroptosis. Collectively, our research provided experimental evidences on the activity and mechanism of ferroptosis induced by IMCA and revealed that IMCA might be a promising therapeutic drug for colorectal cancer.
RESUMEN
[This corrects the article DOI: 10.1155/2020/1675613.].
RESUMEN
Macroautophagy, a key player in protein quality control, is proposed to be systematically impaired in distinct tissues and causes coordinated disruption of protein homeostasis and ageing throughout the body. Although tissue-specific changes in autophagy and ageing have been extensively explored, the mechanism underlying the inter-tissue regulation of autophagy with ageing is poorly understood. Here, we show that a secreted microRNA, mir-83/miR-29, controls the age-related decrease in macroautophagy across tissues in Caenorhabditis elegans. Upregulated in the intestine by hsf-1/HSF1 with age, mir-83 is transported across tissues potentially via extracellular vesicles and disrupts macroautophagy by suppressing CUP-5/MCOLN, a vital autophagy regulator, autonomously in the intestine as well as non-autonomously in body wall muscle. Mutating mir-83 thereby enhances macroautophagy in different tissues, promoting protein homeostasis and longevity. These findings thus identify a microRNA-based mechanism to coordinate the decreasing macroautophagy in various tissues with age.
Asunto(s)
Envejecimiento/genética , Caenorhabditis elegans/genética , Macroautofagia/genética , MicroARNs/genética , Animales , Autofagia/genética , Proteínas de Caenorhabditis elegans/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/metabolismo , Intestinos , Proteínas de la Membrana/metabolismo , MicroARNs/metabolismo , Músculos/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Artificial Z scheme photocatalysis has been considered as a promising strategy for producing the clean energy source of hydrogen gas. The core of the Z scheme is a two-step excitation process in a tandem structured photosystem aiming to satisfy both the criteria of wide range solar spectrum absorption and strong thermodynamic driving force for photolysis reactions. Therefore, efficient connection and matching between the two photosystems is the key to improve the photocatalytic activity. Recently, new progress has been achieved concerning the principles and applications of state-of-the-art solid-state Z schematic systems to enhance the photocatalytic efficiency and repress competitive reactions. This review summarizes the latest approaches to all-solid-state Z schemes for photocatalytic water splitting, including new tandem structures, new morphologies, and new connection modes to improve light absorption as well as carrier transportation. The challenges for developing novel high performance Z scheme photocatalysts are also discussed.
RESUMEN
microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs, which suppress their target mRNAs at the post-transcriptional level. miRNAs play key roles in tumor metastasis. The aim of the present study was to investigate the expression of miRNA-32 (miR-32) on the biological behavior of the human gastric cancer cell line, SGC-7901. SGC-7901 cells were transfected with miR-32-mimic, miR-32-inhibitor and empty plasmid vectors using Lipofectamine™ 2000. The expression of GFP was observed by fluorescent microscopy and miR-32 gene expression was detected by quantitative polymerase chain reaction. The cell counting kit-8 assay was performed to evaluate the effect of miR-32 expression on cell proliferation in vitro. Alterations in the migration and metastatic potential of SGC-7901 cells, prior to and following miR-32 gene transfection, were assayed by cell chemotactic migration and invasion tests. The results of the current study showed that the proliferation rate of the transfected SGC-7901 cells overexpressing miR-32 is reduced and cell chemotactic migration and invasion potentials is markedly reduced following miR-32-mimic transfection (P<0.05). In addition, the results demonstrated that overexpression of miR-32 greatly inhibits the proliferation and decreases the migration and invasion capabilities of SGC-7901 cells in vitro.