Dietary caloric input and tumor growth accelerate senescence and modulate liver and adipose tissue crosstalk

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 7, 2025

Metabolic alterations are related to tumorigenesis and other age-related diseases that accelerated by "Westernized" diets. In fact, hypercaloric nutrition is associated with an increased incidence of cancers faster aging. Conversely, lifespan-extending strategies, such as caloric restriction, impose beneficial effects on both processes. Here, we investigated the metabolic consequences hypercaloric-induced aging tumor growth in female mice. Our findings indicate a high-fat high-sucrose diet increases mainly due boosted oxidation glucose fatty acids. Consequently, through expression lactate, IGFBP3, PTHLH, tumors modulate liver white adipose tissue metabolism. liver, induced fibrosis accelerates senescence process, despite lower systemic pro-inflammatory state. Importantly, induces wasting browning tissue, thereby reversing diet-induced insulin resistance. Finally, suggest alters liver-adipose crosstalk upregulates Fgf21, senescence, negatively modulates lipids carbohydrates metabolism even caloric-restricted-fed Physiological responses different dietary regimens process and, consequently, biology tissues, WAT during growth.

Language: Английский

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Structural robustness and temporal vulnerability of the starvation-responsive metabolic network in healthy and obese mouse liver

Science Signaling, Journal Year: 2025, Volume and Issue: 18(883)

Published: April 22, 2025

Adaptation to starvation is a multimolecular and temporally ordered process. We sought elucidate how the healthy liver regulates various molecules in manner during obesity disrupts this used multiomic data collected from plasma livers of wild-type leptin-deficient obese ( ob / ) mice at multiple time points construct starvation-responsive metabolic network that included responsive their regulatory relationships. Analysis structure showed mice, key for energy homeostasis, ATP AMP, acted as hub regulate reactions network. Although neither nor AMP was structural properties were maintained. In through processes coordinated by molecules, including positively or negatively coregulated. By contrast, both temporal order coregulation disrupted mice. These results suggest responds structurally robust but obesity-associated loss responsiveness molecules. addition, we propose alters response intermittent fasting.

Language: Английский

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Feeding disruptions lead to a significant increase in disease modules in adult mice

Heliyon, Journal Year: 2025, Volume and Issue: 11(2), P. e41774 - e41774

Published: Jan. 1, 2025

Feeding disruption is closely linked to numerous diseases, yet the underlying molecular mechanisms remain an important but unresolved issue at level. We hypothesize that, network level, dietary disruptions can alter gene co-expression patterns, leading increase in disease-associated modules, and thereby elevating likelihood of disease occurrence. Here, we investigate this hypothesis using transcriptomic data from a large cohort adult mice subjected feeding disruptions. Our computational analysis indicates that altered schedules significantly disease-related modules mouse livers, well before aging onset. Conversely, calorie restriction reduces these modules. This provides critical missing link between disease.

Language: Английский

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Tissue-specific effects of dietary protein on cellular senescence are mediated by branched-chain amino acids

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract Dietary protein is a key regulator of healthy aging in both mice and humans. In mice, reducing dietary levels the branched-chain amino acids (BCAAs) recapitulates many benefits low diet; BCAA-restricted diets extend lifespan, reduce frailty, improve metabolic health, while BCAA supplementation shortens promotes obesity, impairs glycemic control. Recently, high have been shown to promote cellular senescence, hallmark implicated age-related diseases, liver mice. Here, we test hypothesis that effects on health cell senescence are mediated by BCAAs. We find BCAAs protects male female from negative consequences normal diets. Further, identify tissue-specific with restriction all three – but not individual protecting hepatic potentiating white adipose tissue. cell-autonomous, lower cultured cells antimycin-A induced senescence. Our results demonstrate direct effect specific component suggest may be highly susceptible interventions.

Language: Английский

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An interactive course program on nutrition for medical students: interdisciplinary development and mixed-methods evaluation

BMC Medical Education, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 23, 2025

Abstract Nutrition plays a crucial role in human and planetary health, as prevailing nutritional patterns significantly contribute to the global non-communicable disease pandemic. Moreover, food system is inextricably linked health deterioration. The relevance of nutrition for individual insufficiently addressed German medical schools. Here, we present two-week course students 8th semester at Charité - Universitätsmedizin Berlin on fasting context health. was developed iteratively along Kern cycle curricula underwent evaluation through mixed-methods design spanning across two consecutive semesters. Assessment involved quantitative questionnaires qualitative interviews. main exploratory outcome overall module rating. Further outcomes encompassed in-depth evaluations specific aspects, including content, teaching methods, instructor performance, subjective experiential aspects. conceptualisation resulted highly participative 37.5 h. learning objectives aimed acquisition technical competences personal competencies four areas: (1) disease; (2) exploration systems; (3) communication subjects nutrition; (4) culinary medicine. Various interactive didactic methodologies were used. 77.8% ( n = 27) participants rated very good or good. conviction that influences increased over (Wilcoxon signed rank test, z -2.82, p 0.005, r 0.57). In interviews 8) its didactical diversity positive group experience appreciated. Our results indicate it could be worthwhile further incorporate education.

Language: Английский

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Transcriptional Heterogeneity and Differential Response of Rod Photoreceptor Pathway Uncovered by Single‐Cell RNA Sequencing of the Aging Mouse Retina

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Visual function deteriorates throughout the natural course of aging. Age-related structural and functional adaptations are observed in retina, light-sensitive neuronal tissue eye where visual perception begins. Molecular mechanisms underlying retinal aging still poorly understood, highlighting need to identify biomarkers for better prognosis alleviation aging-associated vision impairment. Here, we investigate dynamics transcriptional dysregulation retina affected pathways within distinct cell types. Using an optimized protocol single-cell RNA sequencing mouse retinas at 3, 12, 18, 24 months, detect a progressive increase number differentially expressed genes across all The extent direction expression changes varies, with photoreceptor, bipolar, Müller cells showing maximum age groups. Furthermore, our analyses uncover transcriptionally distinct, heterogeneous subpopulations rod photoreceptors bipolar cells, distributed areas retina. Our findings provide plausible molecular explanation enhanced susceptibility correlate loss scotopic sensitivity elderly individuals.

Language: Английский

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Prioritization of prognostic biomarkers regulated by calorie restriction in colon cancer through integrated biosignature analysis

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 20, 2025

Colorectal cancer (CRC) remains a critical global health challenge, ranking second in cancer-related mortality and third incidence as of 2018, with risk increasing age. Addressing its rising burden requires early diagnosis, prognostic biomarkers, effective therapeutic strategies. Emerging evidence suggests that calorie restriction may mitigate aging-related functional decline influence CRC progression, yet the molecular markers mechanisms remain poorly understood. In this study, we analyzed GSE24432 dataset, using multiple computational databases to screen differentially expressed genes (DEGs) associated CRC. Functional annotations, including Gene Ontology (GO), KEGG pathway analysis, gene set enrichment analysis (GSEA), were undertaken explore potential underlying pathways pathogenesis. Kaplan Meier Cox proportional hazards regression analyses conducted establish diagnostic significance hub genes. The validation test was via databases. Our investigation identified 50 DEGs, cutoff criteria, p. adj < 0.05, |log2FC|> 0.3. GO results revealed extensive crosstalk cellular components mRNA ribosome biogenesis, AMPK signaling, p53 signaling following restriction. To understand how these DEGs drive biological reactions, sorted according score > 3 term obtained 14 most relevant terms. Further CHORD showed are enriched biogenesis protein synthesis. (GSEA) involvement several hallmarks, such tissue invasion metastasis (p 0.001), tumor-promoting inflammation resisting cell death 0.01), replicative immortality 0.05). Survival higher expression 7 genes, CDKN2A 0.05), RPL9 0.02), TUBB6 RPS15A lower CDKN1B NPM1 RALA correlated shorter survival colon cancer. However, cross-reference decreased expressions while increased Several tests from high is overall rates, indicating target could serve more reliable biomarker for prognosis. These findings potentially facilitate development precision-based energy interventions management, offering promising prospects targeted strategies patients.

Language: Английский

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Quantification of healthspan in aging mice: introducing FAMY and GRAIL

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 4203 - 4215

Published: May 17, 2024

Language: Английский

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Sex-Specific Variation in Metabolic Responses to Diet

Published: July 16, 2024

Suboptimal nutrition is a leading cause of cardiometabolic disease and mortality. Biological sex variable that can play role in individual response to nutritional factors may modulate the impact on disease. This narrative review explores intricate interplay between sex, nutrition, health outcomes, consequent importance considering research, dietary recommendations, management. We examine how various patterns, including Mediterranean diet, macronutrient content quality, Western energy restriction associate with or affect metabolic risk. Understanding influences diet inform precision interventions approaches for prevention

Language: Английский

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Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 7, 2023

In defiance of the paradigm that calories from all sources are equivalent, we and others have shown dietary protein is a dominant regulator healthy aging. The restriction or branched-chain amino acid isoleucine promotes healthspan extends lifespan when initiated in young adult mice. However, many interventions less efficacious even deleterious aged animals. Here, investigate physiological, metabolic, molecular consequences consuming diet with 67% reduction acids (Low AA), alone Ile), male female C57BL/6J.Nia mice starting at 20 months age. We find both regimens effectively reduce adiposity improve glucose tolerance, which were benefits not mediated by reduced calorie intake. Both diets specific aspects frailty, slow multiple indicators aging rate, rejuvenate heart liver level. These results demonstrate Low AA Ile can drive youthful physiological signatures, support possibility these could help to promote older adults.

Language: Английский

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